ACC 2011

NEW ORLEANS – Preoperative hyponatremia was common in patients undergoing cardiac surgery and associated with a dramatic increase in the risk of death and surgical complications in a large retrospective analysis.

Of the 4,370 patients who underwent cardiac surgery between 2002 and 2009 at the Ohio State Medical Center in Columbus, 931 (21%) had hyponatremia, defined as serum sodium less than 135 mEq/L on at least one of three sodium tests obtained before surgery.

In unadjusted analysis, hyponatremic patients had significantly higher rates than did those without hyponatremia of early mortality (9% vs. 4%), late mortality (24% vs. 15.6%), longer mean hospital length of stay (12.6 days vs. 8.2 days), and operative complications (13% vs. 7%), Dr. Juan Crestanello and his colleagues reported in a poster at the annual meeting of the American College of Cardiology.

This isn’t all that surprising since hyponatremic patients were sicker at baseline, but the poor outcomes remained, even after adjustment for a slew of baseline clinical and operative variables.

In multivariable logistic regression analysis, preoperative hyponatremia was independently associated with a 31% increase in overall mortality, a 52% increase in early mortality, and a 56% increase in late mortality, said Dr. Crestanello, a thoracic surgeon at the medical center.

Hyponatremia also significantly increased the risk of operative complications by 30%, pulmonary complications by 73%, renal failure requiring dialysis by 64%, and hospital length of stay by 26%. Infectious and neurologic complications were not independently associated with preoperative hyponatremia.

"Hyponatremia identifies a group of patients at higher risk for cardiac surgery," Dr. Crestanello said in an interview. "It constitutes another tool to risk-stratify these patients and will help surgeons advise patients of their risk associated with surgery."

At baseline, patients with hyponatremia had a significantly lower mean ejection fraction than did patients without hyponatremia (39% vs. 46%), higher mean pulmonary artery pressure (32 mmHg vs. 28 mmHg), and higher incidence of comorbidities, including diabetes (47% vs. 34%), chronic obstructive pulmonary disease (24.5% vs. 18%), and history of a previous MI (44.5% vs. 35.6%).

Hyponatremic patients also had significantly higher New York Heart Association functional class, higher surgical risk as predicted by the European System for Cardiac Operative Risk Evaluation (19% vs. 9%) and underwent more complex surgical procedures including coronary artery bypass surgery with valve replacement and ventricular-assist device placement.

Their mean age was 62 years, 66.5% were male, and the mean sodium level was 134 mEq/L.

Sodium levels are one of the most common laboratory values measured and are routinely obtained preoperatively.

"In spite of being widely available, they are often overlooked," Dr. Crestanello said.

Data on other factors that may have influenced serum sodium like medications, glucose levels, and fluid use were not accounted for in the study because of its retrospective nature, he noted.

When asked to speculate on the mechanism behind the association between hyponatremia and poor outcomes, Dr. Crestanello said they are not well understood. "Obviously, hyponatremia is a marker for high-risk patients, but at the same time it is likely that it has pathophysiological effects on its own ... hyponatremia is also associated with changes in the neurohormonal milieu that, by itself, can have deleterious effects."

The analysis was based on data from electronic medical records, the Society of Thoracic Surgery database, and Social Security Death Index. Mean follow-up was 2.2 years.

The authors plan to analyze the effects that correcting preoperative hyponatremia has on outcomes of cardiac surgery. The current study was supported by a grant from Biogen Inc.

NEW ORLEANS – Preoperative hyponatremia was common in patients undergoing cardiac surgery and associated with a dramatic increase in the risk of death and surgical complications in a large retrospective analysis.

Of the 4,370 patients who underwent cardiac surgery between 2002 and 2009 at the Ohio State Medical Center in Columbus, 931 (21%) had hyponatremia, defined as serum sodium less than 135 mEq/L on at least one of three sodium tests obtained before surgery.

In unadjusted analysis, hyponatremic patients had significantly higher rates than did those without hyponatremia of early mortality (9% vs. 4%), late mortality (24% vs. 15.6%), longer mean hospital length of stay (12.6 days vs. 8.2 days), and operative complications (13% vs. 7%), Dr. Juan Crestanello and his colleagues reported in a poster at the annual meeting of the American College of Cardiology.

This isn’t all that surprising since hyponatremic patients were sicker at baseline, but the poor outcomes remained, even after adjustment for a slew of baseline clinical and operative variables.

In multivariable logistic regression analysis, preoperative hyponatremia was independently associated with a 31% increase in overall mortality, a 52% increase in early mortality, and a 56% increase in late mortality, said Dr. Crestanello, a thoracic surgeon at the medical center.

Hyponatremia also significantly increased the risk of operative complications by 30%, pulmonary complications by 73%, renal failure requiring dialysis by 64%, and hospital length of stay by 26%. Infectious and neurologic complications were not independently associated with preoperative hyponatremia.

"Hyponatremia identifies a group of patients at higher risk for cardiac surgery," Dr. Crestanello said in an interview. "It constitutes another tool to risk-stratify these patients and will help surgeons advise patients of their risk associated with surgery."

At baseline, patients with hyponatremia had a significantly lower mean ejection fraction than did patients without hyponatremia (39% vs. 46%), higher mean pulmonary artery pressure (32 mmHg vs. 28 mmHg), and higher incidence of comorbidities, including diabetes (47% vs. 34%), chronic obstructive pulmonary disease (24.5% vs. 18%), and history of a previous MI (44.5% vs. 35.6%).

Hyponatremic patients also had significantly higher New York Heart Association functional class, higher surgical risk as predicted by the European System for Cardiac Operative Risk Evaluation (19% vs. 9%) and underwent more complex surgical procedures including coronary artery bypass surgery with valve replacement and ventricular-assist device placement.

Their mean age was 62 years, 66.5% were male, and the mean sodium level was 134 mEq/L.

Sodium levels are one of the most common laboratory values measured and are routinely obtained preoperatively.

"In spite of being widely available, they are often overlooked," Dr. Crestanello said.

Data on other factors that may have influenced serum sodium like medications, glucose levels, and fluid use were not accounted for in the study because of its retrospective nature, he noted.

When asked to speculate on the mechanism behind the association between hyponatremia and poor outcomes, Dr. Crestanello said they are not well understood. "Obviously, hyponatremia is a marker for high-risk patients, but at the same time it is likely that it has pathophysiological effects on its own ... hyponatremia is also associated with changes in the neurohormonal milieu that, by itself, can have deleterious effects."

The analysis was based on data from electronic medical records, the Society of Thoracic Surgery database, and Social Security Death Index. Mean follow-up was 2.2 years.

The authors plan to analyze the effects that correcting preoperative hyponatremia has on outcomes of cardiac surgery. The current study was supported by a grant from Biogen Inc.

NEW ORLEANS – Preoperative hyponatremia was common in patients undergoing cardiac surgery and associated with a dramatic increase in the risk of death and surgical complications in a large retrospective analysis.

Of the 4,370 patients who underwent cardiac surgery between 2002 and 2009 at the Ohio State Medical Center in Columbus, 931 (21%) had hyponatremia, defined as serum sodium less than 135 mEq/L on at least one of three sodium tests obtained before surgery.

In unadjusted analysis, hyponatremic patients had significantly higher rates than did those without hyponatremia of early mortality (9% vs. 4%), late mortality (24% vs. 15.6%), longer mean hospital length of stay (12.6 days vs. 8.2 days), and operative complications (13% vs. 7%), Dr. Juan Crestanello and his colleagues reported in a poster at the annual meeting of the American College of Cardiology.

This isn’t all that surprising since hyponatremic patients were sicker at baseline, but the poor outcomes remained, even after adjustment for a slew of baseline clinical and operative variables.

In multivariable logistic regression analysis, preoperative hyponatremia was independently associated with a 31% increase in overall mortality, a 52% increase in early mortality, and a 56% increase in late mortality, said Dr. Crestanello, a thoracic surgeon at the medical center.

Hyponatremia also significantly increased the risk of operative complications by 30%, pulmonary complications by 73%, renal failure requiring dialysis by 64%, and hospital length of stay by 26%. Infectious and neurologic complications were not independently associated with preoperative hyponatremia.

"Hyponatremia identifies a group of patients at higher risk for cardiac surgery," Dr. Crestanello said in an interview. "It constitutes another tool to risk-stratify these patients and will help surgeons advise patients of their risk associated with surgery."

At baseline, patients with hyponatremia had a significantly lower mean ejection fraction than did patients without hyponatremia (39% vs. 46%), higher mean pulmonary artery pressure (32 mmHg vs. 28 mmHg), and higher incidence of comorbidities, including diabetes (47% vs. 34%), chronic obstructive pulmonary disease (24.5% vs. 18%), and history of a previous MI (44.5% vs. 35.6%).

Hyponatremic patients also had significantly higher New York Heart Association functional class, higher surgical risk as predicted by the European System for Cardiac Operative Risk Evaluation (19% vs. 9%) and underwent more complex surgical procedures including coronary artery bypass surgery with valve replacement and ventricular-assist device placement.

Their mean age was 62 years, 66.5% were male, and the mean sodium level was 134 mEq/L.

Sodium levels are one of the most common laboratory values measured and are routinely obtained preoperatively.

"In spite of being widely available, they are often overlooked," Dr. Crestanello said.

Data on other factors that may have influenced serum sodium like medications, glucose levels, and fluid use were not accounted for in the study because of its retrospective nature, he noted.

When asked to speculate on the mechanism behind the association between hyponatremia and poor outcomes, Dr. Crestanello said they are not well understood. "Obviously, hyponatremia is a marker for high-risk patients, but at the same time it is likely that it has pathophysiological effects on its own ... hyponatremia is also associated with changes in the neurohormonal milieu that, by itself, can have deleterious effects."

The analysis was based on data from electronic medical records, the Society of Thoracic Surgery database, and Social Security Death Index. Mean follow-up was 2.2 years.

The authors plan to analyze the effects that correcting preoperative hyponatremia has on outcomes of cardiac surgery. The current study was supported by a grant from Biogen Inc.

NEW ORLEANS – Preoperative hyponatremia was common in patients undergoing cardiac surgery and associated with a dramatic increased the risk of death and surgical complications in a large retrospective analysis.

Of the 4,370 patients who underwent cardiac surgery between 2002 and 2009 at the Ohio State Medical Center in Columbus, 931 (21%) had hyponatremia, defined as serum sodium less than 135 mEq/L on at least one of three sodium tests obtained before surgery.

In unadjusted analysis, hyponatremic patients had significantly higher rates than did those without hyponatremia of early mortality (9% vs. 4%), late mortality (24% vs. 15.6%), longer mean hospital length of stay (12.6 days vs. 8.2 days), and operative complications (13% vs. 7%), Dr. Juan Crestanello and his colleagues reported in a poster at the annual meeting of the American College of Cardiology.

This isn’t all that surprising since hyponatremic patients were sicker at baseline, but the poor outcomes remained, even after adjustment for a slew of baseline clinical and operative variables.

In multivariable logistic regression analysis, preoperative hyponatremia was independently associated with a 31% increase in overall mortality, a 52% increase in early mortality, and a 56% increase in late mortality, said Dr. Crestanello, a thoracic surgeon at the medical center.

Hyponatremia also significantly increased the risk of operative complications by 30%, pulmonary complications by 73%, renal failure requiring dialysis by 64%, and hospital length of stay by 26%. Infectious and neurologic complications were not independently associated with preoperative hyponatremia.

"Hyponatremia identifies a group of patients at higher risk for cardiac surgery," Dr. Crestanello said in an interview. "It constitutes another tool to risk-stratify these patients and will help surgeons advice patients of their risk associated with surgery."

At baseline, patients with hyponatremia had a significantly lower mean ejection fraction than did patients without hyponatremia (39% vs. 46%), higher mean pulmonary artery pressure (32 mmHg vs. 28 mmHg), and higher incidence of comorbidities, including diabetes (47% vs. 34%), chronic obstructive pulmonary disease (24.5% vs. 18%), and history of a previous MI (44.5% vs. 35.6%).

Hyponatremic patients also had significantly higher New York Heart Association functional class, higher surgical risk as predicted by the European System for Cardiac Operative Risk Evaluation (19% vs. 9%) and underwent more complex surgical procedures including coronary artery bypass surgery with valve replacement and ventricular-assist device placement.

Their mean age was 62 years, 66.5% were male, and the mean sodium level was 134 mEq/L.

Sodium levels are one of the most common laboratory values measured and are routinely obtained preoperatively.

"In spite of being widely available, they are often overlooked," Dr. Crestanello said.

Data on other factors that may have influenced serum sodium like medications, glucose levels, and fluid use were not accounted for in the study because of its retrospective nature, he noted.

When asked to speculate on the mechanism behind the association between hyponatremia and poor outcomes, Dr. Crestanello said they are not well understood. "Obviously, hyponatremia is a marker for high-risk patients, but at the same time it is likely that it has pathophysiological effects on its own ... hyponatremia is also associated with changes in the neurohormonal milieu that, by itself, can have deleterious effects."

The analysis was based on data from electronic medical records, the Society of Thoracic Surgery database, and Social Security Death Index. Mean follow-up was 2.2 years.

The authors plan to analyze the effects that correcting preoperative hyponatremia has on outcomes of cardiac surgery. The current study was supported by a grant from Biogen Inc.

NEW ORLEANS – Preoperative hyponatremia was common in patients undergoing cardiac surgery and associated with a dramatic increased the risk of death and surgical complications in a large retrospective analysis.

Of the 4,370 patients who underwent cardiac surgery between 2002 and 2009 at the Ohio State Medical Center in Columbus, 931 (21%) had hyponatremia, defined as serum sodium less than 135 mEq/L on at least one of three sodium tests obtained before surgery.

In unadjusted analysis, hyponatremic patients had significantly higher rates than did those without hyponatremia of early mortality (9% vs. 4%), late mortality (24% vs. 15.6%), longer mean hospital length of stay (12.6 days vs. 8.2 days), and operative complications (13% vs. 7%), Dr. Juan Crestanello and his colleagues reported in a poster at the annual meeting of the American College of Cardiology.

This isn’t all that surprising since hyponatremic patients were sicker at baseline, but the poor outcomes remained, even after adjustment for a slew of baseline clinical and operative variables.

In multivariable logistic regression analysis, preoperative hyponatremia was independently associated with a 31% increase in overall mortality, a 52% increase in early mortality, and a 56% increase in late mortality, said Dr. Crestanello, a thoracic surgeon at the medical center.

Hyponatremia also significantly increased the risk of operative complications by 30%, pulmonary complications by 73%, renal failure requiring dialysis by 64%, and hospital length of stay by 26%. Infectious and neurologic complications were not independently associated with preoperative hyponatremia.

"Hyponatremia identifies a group of patients at higher risk for cardiac surgery," Dr. Crestanello said in an interview. "It constitutes another tool to risk-stratify these patients and will help surgeons advice patients of their risk associated with surgery."

At baseline, patients with hyponatremia had a significantly lower mean ejection fraction than did patients without hyponatremia (39% vs. 46%), higher mean pulmonary artery pressure (32 mmHg vs. 28 mmHg), and higher incidence of comorbidities, including diabetes (47% vs. 34%), chronic obstructive pulmonary disease (24.5% vs. 18%), and history of a previous MI (44.5% vs. 35.6%).

Hyponatremic patients also had significantly higher New York Heart Association functional class, higher surgical risk as predicted by the European System for Cardiac Operative Risk Evaluation (19% vs. 9%) and underwent more complex surgical procedures including coronary artery bypass surgery with valve replacement and ventricular-assist device placement.

Their mean age was 62 years, 66.5% were male, and the mean sodium level was 134 mEq/L.

Sodium levels are one of the most common laboratory values measured and are routinely obtained preoperatively.

"In spite of being widely available, they are often overlooked," Dr. Crestanello said.

Data on other factors that may have influenced serum sodium like medications, glucose levels, and fluid use were not accounted for in the study because of its retrospective nature, he noted.

When asked to speculate on the mechanism behind the association between hyponatremia and poor outcomes, Dr. Crestanello said they are not well understood. "Obviously, hyponatremia is a marker for high-risk patients, but at the same time it is likely that it has pathophysiological effects on its own ... hyponatremia is also associated with changes in the neurohormonal milieu that, by itself, can have deleterious effects."

The analysis was based on data from electronic medical records, the Society of Thoracic Surgery database, and Social Security Death Index. Mean follow-up was 2.2 years.

The authors plan to analyze the effects that correcting preoperative hyponatremia has on outcomes of cardiac surgery. The current study was supported by a grant from Biogen Inc.

NEW ORLEANS – Preoperative hyponatremia was common in patients undergoing cardiac surgery and associated with a dramatic increased the risk of death and surgical complications in a large retrospective analysis.

Of the 4,370 patients who underwent cardiac surgery between 2002 and 2009 at the Ohio State Medical Center in Columbus, 931 (21%) had hyponatremia, defined as serum sodium less than 135 mEq/L on at least one of three sodium tests obtained before surgery.

In unadjusted analysis, hyponatremic patients had significantly higher rates than did those without hyponatremia of early mortality (9% vs. 4%), late mortality (24% vs. 15.6%), longer mean hospital length of stay (12.6 days vs. 8.2 days), and operative complications (13% vs. 7%), Dr. Juan Crestanello and his colleagues reported in a poster at the annual meeting of the American College of Cardiology.

This isn’t all that surprising since hyponatremic patients were sicker at baseline, but the poor outcomes remained, even after adjustment for a slew of baseline clinical and operative variables.

In multivariable logistic regression analysis, preoperative hyponatremia was independently associated with a 31% increase in overall mortality, a 52% increase in early mortality, and a 56% increase in late mortality, said Dr. Crestanello, a thoracic surgeon at the medical center.

Hyponatremia also significantly increased the risk of operative complications by 30%, pulmonary complications by 73%, renal failure requiring dialysis by 64%, and hospital length of stay by 26%. Infectious and neurologic complications were not independently associated with preoperative hyponatremia.

"Hyponatremia identifies a group of patients at higher risk for cardiac surgery," Dr. Crestanello said in an interview. "It constitutes another tool to risk-stratify these patients and will help surgeons advice patients of their risk associated with surgery."

At baseline, patients with hyponatremia had a significantly lower mean ejection fraction than did patients without hyponatremia (39% vs. 46%), higher mean pulmonary artery pressure (32 mmHg vs. 28 mmHg), and higher incidence of comorbidities, including diabetes (47% vs. 34%), chronic obstructive pulmonary disease (24.5% vs. 18%), and history of a previous MI (44.5% vs. 35.6%).

Hyponatremic patients also had significantly higher New York Heart Association functional class, higher surgical risk as predicted by the European System for Cardiac Operative Risk Evaluation (19% vs. 9%) and underwent more complex surgical procedures including coronary artery bypass surgery with valve replacement and ventricular-assist device placement.

Their mean age was 62 years, 66.5% were male, and the mean sodium level was 134 mEq/L.

Sodium levels are one of the most common laboratory values measured and are routinely obtained preoperatively.

"In spite of being widely available, they are often overlooked," Dr. Crestanello said.

Data on other factors that may have influenced serum sodium like medications, glucose levels, and fluid use were not accounted for in the study because of its retrospective nature, he noted.

When asked to speculate on the mechanism behind the association between hyponatremia and poor outcomes, Dr. Crestanello said they are not well understood. "Obviously, hyponatremia is a marker for high-risk patients, but at the same time it is likely that it has pathophysiological effects on its own ... hyponatremia is also associated with changes in the neurohormonal milieu that, by itself, can have deleterious effects."

The analysis was based on data from electronic medical records, the Society of Thoracic Surgery database, and Social Security Death Index. Mean follow-up was 2.2 years.

The authors plan to analyze the effects that correcting preoperative hyponatremia has on outcomes of cardiac surgery. The current study was supported by a grant from Biogen Inc.

NEW ORLEANS – About 12% of the more than 140,000 Americans who underwent elective coronary artery stenting during 2009-2010 had an inappropriate procedure, based on an analysis of data from a national coronary stent registry maintained by the American College of Cardiology.

In contrast, the rate of inappropriate procedures was 1% in the larger group of more than 355,000 patients who had an acute need for percutaneous coronary interventions (PCI) during the period studied, Dr. Paul S. Chan said at the annual meeting of the American College of Cardiology.

The analysis also showed a striking hospital-to-hospital variation in the rate of elective PCI cases flagged as inappropriate. About 25% of the hospitals doing elective cases had a rate below 6%; another quarter had a rate of 17% or higher. Yet some hospitals had inappropriate rates that exceeded 30%.

Starting in May 2011, the ACC will start reporting data from this analysis to each of the more than 1,000 participating U.S. hospitals. By carefully reviewing cases that have been flagged as inappropriate, it is hoped that hospitals will learn from their mistakes and drive down the inappropriate rate, especially for elective PCIs, said Dr. Chan, a cardiologist at the Mid-America Heart Institute of Saint Luke’s Hospital in Kansas City, Mo.

The ACC collects the PCI data through the CathPCI portion of its National Cardiovascular Data Registry (NCDR). Dr. Chan and his associates rated each procedure they reviewed as appropriate, inappropriate, or uncertain based on comprehensive criteria established by an ACC expert panel (J. Am. Coll. Card. 2009;53:530-53).

But even with feedback and review of inappropriate PCIs, the rate of these cases will probably never drop to zero, he said.

Other experts hailed the analysis and feedback program as an advance that will improve U.S. use of PCI, but they also cautioned that the findings must be interpreted carefully.

"About 25% of the interventional cases in my practice would be categorized as inappropriate," commented Dr. Edward J. McNulty, an interventional cardiologist at Kaiser Permanente in San Francisco. "I get most of my patients from surgeons or other interventional cardiologists who feel the patients are too high risk. I do a lot of left main and multivessel PCI. There is no way that I can explain on the NCDR form why I consider these patients appropriate. The NCDR data don’t allow you to appreciate nuances. The criteria tend to penalize physicians who deviate from the average [by performing] complex cases."

Additionally, the way patients’ drug use gets recorded on the day of hospitalization is problematic, as patients may stop a chronically-used drug on the day before entering the hospital and be erroneously recorded as not being on a therapy. Another issue is misclassification of symptoms, such as a patient who perceives ischemic chest pain as shortness of breath.

"I believe that inappropriate PCIs occur, and these results can certainly show signals. But within the ‘inappropriate’ procedures are some cases with mitigating circumstances," Dr. McNulty said in an interview.

"There are cases that you know are appropriate, but you can’t get at them adequately with the [NCDR] data forms," agreed Dr. William S. Weintraub, chief of cardiology at the Christiana Care Health System in Newark, Del. "We need to be very careful about what we say about any institution with inappropriate cases." The analysis results are best used to identify inappropriate cases to hospitals so that hospital staffs can closely study these cases, determine if they were truly inappropriate, and if so, to try to find the problems and fix them, Dr. Weintraub said in an interview.

The ACC expert panel published appropriateness criteria for 198 different clinical scenarios based on six separate clinical elements in February 2009. Dr. Chan and his associates applied the criteria to 500,154 U.S. cases that were treated with PCI during July 2009 through the end of September 2010. The criteria sorted cases into three categories: appropriate, inappropriate, or uncertain. Inappropriate cases were situations where the expected negative consequences of the procedure exceeded the expected benefits.

PCI performed for an acute problem (such as high-risk unstable angina or MI) occurred in 71% of the cases. In this group, 99% of the cases were rated as appropriate, 1% as inappropriate, and fewer than 1% as uncertain. The remaining 29% of PCI procedures occurred in elective cases, of which 50% were rated as appropriate, 12% as inappropriate, and 38% as uncertain, Dr. Chan reported.

The three most common reasons for rating a case as inappropriate included patients with no ischemia, patients with mild ischemia, and asymptomatic patients, he said in an interview.

To address this issue, the ACC should develop a "real-time decision aid" that encourages interventionalists to "take a step back" during a catheterization to review a patient’s history and make a more informed decision on the need for PCI, Dr. Chan said. The interventional cardiologist should review the degree of symptoms a patient has had and the evidence of ischemia, and take those findings into account when deciding whether the patient needs PCI.

Dr. Chan and Dr. McNulty said they had no disclosures.

NEW ORLEANS – About 12% of the more than 140,000 Americans who underwent elective coronary artery stenting during 2009-2010 had an inappropriate procedure, based on an analysis of data from a national coronary stent registry maintained by the American College of Cardiology.

In contrast, the rate of inappropriate procedures was 1% in the larger group of more than 355,000 patients who had an acute need for percutaneous coronary interventions (PCI) during the period studied, Dr. Paul S. Chan said at the annual meeting of the American College of Cardiology.

The analysis also showed a striking hospital-to-hospital variation in the rate of elective PCI cases flagged as inappropriate. About 25% of the hospitals doing elective cases had a rate below 6%; another quarter had a rate of 17% or higher. Yet some hospitals had inappropriate rates that exceeded 30%.

Starting in May 2011, the ACC will start reporting data from this analysis to each of the more than 1,000 participating U.S. hospitals. By carefully reviewing cases that have been flagged as inappropriate, it is hoped that hospitals will learn from their mistakes and drive down the inappropriate rate, especially for elective PCIs, said Dr. Chan, a cardiologist at the Mid-America Heart Institute of Saint Luke’s Hospital in Kansas City, Mo.

The ACC collects the PCI data through the CathPCI portion of its National Cardiovascular Data Registry (NCDR). Dr. Chan and his associates rated each procedure they reviewed as appropriate, inappropriate, or uncertain based on comprehensive criteria established by an ACC expert panel (J. Am. Coll. Card. 2009;53:530-53).

But even with feedback and review of inappropriate PCIs, the rate of these cases will probably never drop to zero, he said.

Other experts hailed the analysis and feedback program as an advance that will improve U.S. use of PCI, but they also cautioned that the findings must be interpreted carefully.

"About 25% of the interventional cases in my practice would be categorized as inappropriate," commented Dr. Edward J. McNulty, an interventional cardiologist at Kaiser Permanente in San Francisco. "I get most of my patients from surgeons or other interventional cardiologists who feel the patients are too high risk. I do a lot of left main and multivessel PCI. There is no way that I can explain on the NCDR form why I consider these patients appropriate. The NCDR data don’t allow you to appreciate nuances. The criteria tend to penalize physicians who deviate from the average [by performing] complex cases."

Additionally, the way patients’ drug use gets recorded on the day of hospitalization is problematic, as patients may stop a chronically-used drug on the day before entering the hospital and be erroneously recorded as not being on a therapy. Another issue is misclassification of symptoms, such as a patient who perceives ischemic chest pain as shortness of breath.

"I believe that inappropriate PCIs occur, and these results can certainly show signals. But within the ‘inappropriate’ procedures are some cases with mitigating circumstances," Dr. McNulty said in an interview.

"There are cases that you know are appropriate, but you can’t get at them adequately with the [NCDR] data forms," agreed Dr. William S. Weintraub, chief of cardiology at the Christiana Care Health System in Newark, Del. "We need to be very careful about what we say about any institution with inappropriate cases." The analysis results are best used to identify inappropriate cases to hospitals so that hospital staffs can closely study these cases, determine if they were truly inappropriate, and if so, to try to find the problems and fix them, Dr. Weintraub said in an interview.

The ACC expert panel published appropriateness criteria for 198 different clinical scenarios based on six separate clinical elements in February 2009. Dr. Chan and his associates applied the criteria to 500,154 U.S. cases that were treated with PCI during July 2009 through the end of September 2010. The criteria sorted cases into three categories: appropriate, inappropriate, or uncertain. Inappropriate cases were situations where the expected negative consequences of the procedure exceeded the expected benefits.

PCI performed for an acute problem (such as high-risk unstable angina or MI) occurred in 71% of the cases. In this group, 99% of the cases were rated as appropriate, 1% as inappropriate, and fewer than 1% as uncertain. The remaining 29% of PCI procedures occurred in elective cases, of which 50% were rated as appropriate, 12% as inappropriate, and 38% as uncertain, Dr. Chan reported.

The three most common reasons for rating a case as inappropriate included patients with no ischemia, patients with mild ischemia, and asymptomatic patients, he said in an interview.

To address this issue, the ACC should develop a "real-time decision aid" that encourages interventionalists to "take a step back" during a catheterization to review a patient’s history and make a more informed decision on the need for PCI, Dr. Chan said. The interventional cardiologist should review the degree of symptoms a patient has had and the evidence of ischemia, and take those findings into account when deciding whether the patient needs PCI.

Dr. Chan and Dr. McNulty said they had no disclosures.

NEW ORLEANS – About 12% of the more than 140,000 Americans who underwent elective coronary artery stenting during 2009-2010 had an inappropriate procedure, based on an analysis of data from a national coronary stent registry maintained by the American College of Cardiology.

In contrast, the rate of inappropriate procedures was 1% in the larger group of more than 355,000 patients who had an acute need for percutaneous coronary interventions (PCI) during the period studied, Dr. Paul S. Chan said at the annual meeting of the American College of Cardiology.

The analysis also showed a striking hospital-to-hospital variation in the rate of elective PCI cases flagged as inappropriate. About 25% of the hospitals doing elective cases had a rate below 6%; another quarter had a rate of 17% or higher. Yet some hospitals had inappropriate rates that exceeded 30%.

Starting in May 2011, the ACC will start reporting data from this analysis to each of the more than 1,000 participating U.S. hospitals. By carefully reviewing cases that have been flagged as inappropriate, it is hoped that hospitals will learn from their mistakes and drive down the inappropriate rate, especially for elective PCIs, said Dr. Chan, a cardiologist at the Mid-America Heart Institute of Saint Luke’s Hospital in Kansas City, Mo.

The ACC collects the PCI data through the CathPCI portion of its National Cardiovascular Data Registry (NCDR). Dr. Chan and his associates rated each procedure they reviewed as appropriate, inappropriate, or uncertain based on comprehensive criteria established by an ACC expert panel (J. Am. Coll. Card. 2009;53:530-53).

But even with feedback and review of inappropriate PCIs, the rate of these cases will probably never drop to zero, he said.

Other experts hailed the analysis and feedback program as an advance that will improve U.S. use of PCI, but they also cautioned that the findings must be interpreted carefully.

"About 25% of the interventional cases in my practice would be categorized as inappropriate," commented Dr. Edward J. McNulty, an interventional cardiologist at Kaiser Permanente in San Francisco. "I get most of my patients from surgeons or other interventional cardiologists who feel the patients are too high risk. I do a lot of left main and multivessel PCI. There is no way that I can explain on the NCDR form why I consider these patients appropriate. The NCDR data don’t allow you to appreciate nuances. The criteria tend to penalize physicians who deviate from the average [by performing] complex cases."

Additionally, the way patients’ drug use gets recorded on the day of hospitalization is problematic, as patients may stop a chronically-used drug on the day before entering the hospital and be erroneously recorded as not being on a therapy. Another issue is misclassification of symptoms, such as a patient who perceives ischemic chest pain as shortness of breath.

"I believe that inappropriate PCIs occur, and these results can certainly show signals. But within the ‘inappropriate’ procedures are some cases with mitigating circumstances," Dr. McNulty said in an interview.

"There are cases that you know are appropriate, but you can’t get at them adequately with the [NCDR] data forms," agreed Dr. William S. Weintraub, chief of cardiology at the Christiana Care Health System in Newark, Del. "We need to be very careful about what we say about any institution with inappropriate cases." The analysis results are best used to identify inappropriate cases to hospitals so that hospital staffs can closely study these cases, determine if they were truly inappropriate, and if so, to try to find the problems and fix them, Dr. Weintraub said in an interview.

The ACC expert panel published appropriateness criteria for 198 different clinical scenarios based on six separate clinical elements in February 2009. Dr. Chan and his associates applied the criteria to 500,154 U.S. cases that were treated with PCI during July 2009 through the end of September 2010. The criteria sorted cases into three categories: appropriate, inappropriate, or uncertain. Inappropriate cases were situations where the expected negative consequences of the procedure exceeded the expected benefits.

PCI performed for an acute problem (such as high-risk unstable angina or MI) occurred in 71% of the cases. In this group, 99% of the cases were rated as appropriate, 1% as inappropriate, and fewer than 1% as uncertain. The remaining 29% of PCI procedures occurred in elective cases, of which 50% were rated as appropriate, 12% as inappropriate, and 38% as uncertain, Dr. Chan reported.

The three most common reasons for rating a case as inappropriate included patients with no ischemia, patients with mild ischemia, and asymptomatic patients, he said in an interview.

To address this issue, the ACC should develop a "real-time decision aid" that encourages interventionalists to "take a step back" during a catheterization to review a patient’s history and make a more informed decision on the need for PCI, Dr. Chan said. The interventional cardiologist should review the degree of symptoms a patient has had and the evidence of ischemia, and take those findings into account when deciding whether the patient needs PCI.

Dr. Chan and Dr. McNulty said they had no disclosures.

NEW ORLEANS – Myocardial viability failed to predict a significant survival benefit from coronary bypass surgery in patients with coronary artery disease and left ventricular dysfunction in the STICH Viability substudy.

The data are surprising and call into question the long-standing practice of assessing myocardial viability as a means to predict clinical benefit from coronary bypass surgery.

The substudy included 610 of the 1,212 patients in the Surgical Treatment for Ischemic Heart Failure (STICH) trial who underwent baseline myocardial viability testing using SPECT or dobutamine echocardiography, or both, and were randomly assigned to aggressive medical therapy with or without coronary artery bypass surgery (CABG).

At a median follow-up of 5 years, 51% of patients without viable myocardium and 37% with viable myocardium died. The presence of viable myocardium significantly reduced the risk of all-cause mortality by 36%, but the survival advantage lost statistical significance in a multivariable analysis that included other prognostic variables, Dr. Robert Bonow reported at the annual meeting of the American College of Cardiology.

The secondary outcome of cardiovascular mortality was also significantly lower in patients with myocardial viability compared with those without myocardial viability, at 29% and 43%, respectively, but once again, the association lost significance in multivariable analysis.

Notably, the secondary composite end point of death plus cardiovascular hospitalization, which is commonly used in heart failure trials, retained significance in multivariable analysis in favor of patients with myocardial viability, occurring in 63% of patients with viable myocardium and 82% of those without.

There was no significant interaction, however, between myocardial viability status and medical versus surgical treatment with respect to mortality, whether assessed according to treatment assigned or to the treatment actually received, said Dr. Bonow, professor of cardiology at Northwestern University in Chicago. Five-year all-cause mortality rates among the 114 patients without myocardial viability were 56% with medical therapy and 42% with CABG. Among the 487 patients with myocardial viability the rates were 35% vs. 31%, respectively.

"The lack of interaction between myocardial viability and benefit from CABG in this study indicates that assessment of myocardial viability, independent of other relevant variables, should not be the deciding factor in selecting the best therapy for patients with ischemic left ventricular function," he said.

Discussant Bernard Gersh, professor of medicine at Mayo Clinic in Rochester, Minn., asked what clinicians should analyze to determine which of their patients with heart failure and coronary disease to send to surgery, particularly in light of the benefits observed with CABG in the primary STICH analysis. Those data showed a 5% reduction in all-cause mortality at 6 years with the addition of CABG to medical therapy.

Dr. Bonow replied, "I think viability may be something you look at in some patients, but the point would be that there are other clinical variables, perhaps coronary anatomy, that one would bring into play."

Dr. Steven Bollings, with the Cardiovascular Center at the University of Michigan in Ann Arbor, said the primary STICH results provide a clear answer that patients with heart failure and left ventricular dysfunction benefit from coronary bypass surgery, but that the viability substudy raises a number of questions. He said that myocardial "may not be the No. 1 criterion by which we send patients to the operating room" and that other variables such as whether the patient has clear distal targets or is robust may be more important.

Dr. Gregg W. Stone of Columbia University, New York, said, "While I admit this is the clearly the best and most important viability study ever done, I don’t know that it definitively answers the question for us that viability doesn’t matter."

He pointed out that the viability data were based on only half of the STICH participants, the subsets were unbalanced with 80% of patients having viable myocardium and that some would say it’s not appropriate to look for interaction testing off of a negative end point.

"What I take away from this is that if there’s viability, I really want to be sure to revascularize," said Dr. Ted E. Feldman of NorthShore University HealthSystem in Evanston, Ill. "But prior to seeing these results, I was inclined to say if there wasn’t viability, not to vascularize. And the results of the trial challenge that historic bias," he added.

STICH Viability was supported by grants from the National Heart, Lung, and Blood Institute and Abbott Laboratories. Dr. Bonow had no relevant disclosures.

NEW ORLEANS – Myocardial viability failed to predict a significant survival benefit from coronary bypass surgery in patients with coronary artery disease and left ventricular dysfunction in the STICH Viability substudy.

The data are surprising and call into question the long-standing practice of assessing myocardial viability as a means to predict clinical benefit from coronary bypass surgery.

The substudy included 610 of the 1,212 patients in the Surgical Treatment for Ischemic Heart Failure (STICH) trial who underwent baseline myocardial viability testing using SPECT or dobutamine echocardiography, or both, and were randomly assigned to aggressive medical therapy with or without coronary artery bypass surgery (CABG).

At a median follow-up of 5 years, 51% of patients without viable myocardium and 37% with viable myocardium died. The presence of viable myocardium significantly reduced the risk of all-cause mortality by 36%, but the survival advantage lost statistical significance in a multivariable analysis that included other prognostic variables, Dr. Robert Bonow reported at the annual meeting of the American College of Cardiology.

The secondary outcome of cardiovascular mortality was also significantly lower in patients with myocardial viability compared with those without myocardial viability, at 29% and 43%, respectively, but once again, the association lost significance in multivariable analysis.

Notably, the secondary composite end point of death plus cardiovascular hospitalization, which is commonly used in heart failure trials, retained significance in multivariable analysis in favor of patients with myocardial viability, occurring in 63% of patients with viable myocardium and 82% of those without.

There was no significant interaction, however, between myocardial viability status and medical versus surgical treatment with respect to mortality, whether assessed according to treatment assigned or to the treatment actually received, said Dr. Bonow, professor of cardiology at Northwestern University in Chicago. Five-year all-cause mortality rates among the 114 patients without myocardial viability were 56% with medical therapy and 42% with CABG. Among the 487 patients with myocardial viability the rates were 35% vs. 31%, respectively.

"The lack of interaction between myocardial viability and benefit from CABG in this study indicates that assessment of myocardial viability, independent of other relevant variables, should not be the deciding factor in selecting the best therapy for patients with ischemic left ventricular function," he said.

Discussant Bernard Gersh, professor of medicine at Mayo Clinic in Rochester, Minn., asked what clinicians should analyze to determine which of their patients with heart failure and coronary disease to send to surgery, particularly in light of the benefits observed with CABG in the primary STICH analysis. Those data showed a 5% reduction in all-cause mortality at 6 years with the addition of CABG to medical therapy.

Dr. Bonow replied, "I think viability may be something you look at in some patients, but the point would be that there are other clinical variables, perhaps coronary anatomy, that one would bring into play."

Dr. Steven Bollings, with the Cardiovascular Center at the University of Michigan in Ann Arbor, said the primary STICH results provide a clear answer that patients with heart failure and left ventricular dysfunction benefit from coronary bypass surgery, but that the viability substudy raises a number of questions. He said that myocardial "may not be the No. 1 criterion by which we send patients to the operating room" and that other variables such as whether the patient has clear distal targets or is robust may be more important.

Dr. Gregg W. Stone of Columbia University, New York, said, "While I admit this is the clearly the best and most important viability study ever done, I don’t know that it definitively answers the question for us that viability doesn’t matter."

He pointed out that the viability data were based on only half of the STICH participants, the subsets were unbalanced with 80% of patients having viable myocardium and that some would say it’s not appropriate to look for interaction testing off of a negative end point.

"What I take away from this is that if there’s viability, I really want to be sure to revascularize," said Dr. Ted E. Feldman of NorthShore University HealthSystem in Evanston, Ill. "But prior to seeing these results, I was inclined to say if there wasn’t viability, not to vascularize. And the results of the trial challenge that historic bias," he added.

STICH Viability was supported by grants from the National Heart, Lung, and Blood Institute and Abbott Laboratories. Dr. Bonow had no relevant disclosures.

NEW ORLEANS – Myocardial viability failed to predict a significant survival benefit from coronary bypass surgery in patients with coronary artery disease and left ventricular dysfunction in the STICH Viability substudy.

The data are surprising and call into question the long-standing practice of assessing myocardial viability as a means to predict clinical benefit from coronary bypass surgery.

The substudy included 610 of the 1,212 patients in the Surgical Treatment for Ischemic Heart Failure (STICH) trial who underwent baseline myocardial viability testing using SPECT or dobutamine echocardiography, or both, and were randomly assigned to aggressive medical therapy with or without coronary artery bypass surgery (CABG).

At a median follow-up of 5 years, 51% of patients without viable myocardium and 37% with viable myocardium died. The presence of viable myocardium significantly reduced the risk of all-cause mortality by 36%, but the survival advantage lost statistical significance in a multivariable analysis that included other prognostic variables, Dr. Robert Bonow reported at the annual meeting of the American College of Cardiology.

The secondary outcome of cardiovascular mortality was also significantly lower in patients with myocardial viability compared with those without myocardial viability, at 29% and 43%, respectively, but once again, the association lost significance in multivariable analysis.

Notably, the secondary composite end point of death plus cardiovascular hospitalization, which is commonly used in heart failure trials, retained significance in multivariable analysis in favor of patients with myocardial viability, occurring in 63% of patients with viable myocardium and 82% of those without.

There was no significant interaction, however, between myocardial viability status and medical versus surgical treatment with respect to mortality, whether assessed according to treatment assigned or to the treatment actually received, said Dr. Bonow, professor of cardiology at Northwestern University in Chicago. Five-year all-cause mortality rates among the 114 patients without myocardial viability were 56% with medical therapy and 42% with CABG. Among the 487 patients with myocardial viability the rates were 35% vs. 31%, respectively.

"The lack of interaction between myocardial viability and benefit from CABG in this study indicates that assessment of myocardial viability, independent of other relevant variables, should not be the deciding factor in selecting the best therapy for patients with ischemic left ventricular function," he said.

Discussant Bernard Gersh, professor of medicine at Mayo Clinic in Rochester, Minn., asked what clinicians should analyze to determine which of their patients with heart failure and coronary disease to send to surgery, particularly in light of the benefits observed with CABG in the primary STICH analysis. Those data showed a 5% reduction in all-cause mortality at 6 years with the addition of CABG to medical therapy.

Dr. Bonow replied, "I think viability may be something you look at in some patients, but the point would be that there are other clinical variables, perhaps coronary anatomy, that one would bring into play."

Dr. Steven Bollings, with the Cardiovascular Center at the University of Michigan in Ann Arbor, said the primary STICH results provide a clear answer that patients with heart failure and left ventricular dysfunction benefit from coronary bypass surgery, but that the viability substudy raises a number of questions. He said that myocardial "may not be the No. 1 criterion by which we send patients to the operating room" and that other variables such as whether the patient has clear distal targets or is robust may be more important.

Dr. Gregg W. Stone of Columbia University, New York, said, "While I admit this is the clearly the best and most important viability study ever done, I don’t know that it definitively answers the question for us that viability doesn’t matter."

He pointed out that the viability data were based on only half of the STICH participants, the subsets were unbalanced with 80% of patients having viable myocardium and that some would say it’s not appropriate to look for interaction testing off of a negative end point.

"What I take away from this is that if there’s viability, I really want to be sure to revascularize," said Dr. Ted E. Feldman of NorthShore University HealthSystem in Evanston, Ill. "But prior to seeing these results, I was inclined to say if there wasn’t viability, not to vascularize. And the results of the trial challenge that historic bias," he added.

STICH Viability was supported by grants from the National Heart, Lung, and Blood Institute and Abbott Laboratories. Dr. Bonow had no relevant disclosures.

NEW ORLEANS – Myocardial viability failed to predict a significant survival benefit from coronary bypass surgery in patients with coronary artery disease and left ventricular dysfunction in the STICH Viability substudy.

The data are surprising and call into question the long-standing practice of assessing myocardial viability as a means to predict clinical benefit from coronary bypass surgery.

The substudy included 610 of the 1,212 patients in the Surgical Treatment for Ischemic Heart Failure (STICH) trial who underwent baseline myocardial viability testing using SPECT or dobutamine echocardiography, or both, and were randomly assigned to aggressive medical therapy with or without coronary artery bypass surgery (CABG).

At a median follow-up of 5 years, 51% of patients without viable myocardium and 37% with viable myocardium died. The presence of viable myocardium significantly reduced the risk of all-cause mortality by 36%, but the survival advantage lost statistical significance in a multivariable analysis that included other prognostic variables, Dr. Robert Bonow reported at the annual meeting of the American College of Cardiology.

The secondary outcome of cardiovascular mortality was also significantly lower in patients with myocardial viability compared with those without myocardial viability, at 29% and 43%, respectively, but once again, the association lost significance in multivariable analysis.

Notably, the secondary composite end point of death plus cardiovascular hospitalization, which is commonly used in heart failure trials, retained significance in multivariable analysis in favor of patients with myocardial viability, occurring in 63% of patients with viable myocardium and 82% of those without.

There was no significant interaction, however, between myocardial viability status and medical versus surgical treatment with respect to mortality, whether assessed according to treatment assigned or to the treatment actually received, said Dr. Bonow, professor of cardiology at Northwestern University in Chicago. Five-year all-cause mortality rates among the 114 patients without myocardial viability were 56% with medical therapy and 42% with CABG. Among the 487 patients with myocardial viability the rates were 35% vs. 31%, respectively.

"The lack of interaction between myocardial viability and benefit from CABG in this study indicates that assessment of myocardial viability, independent of other relevant variables, should not be the deciding factor in selecting the best therapy for patients with ischemic left ventricular function," he said.

Discussant Bernard Gersh, professor of medicine at Mayo Clinic in Rochester, Minn., asked what clinicians should analyze to determine which of their patients with heart failure and coronary disease to send to surgery, particularly in light of the benefits observed with CABG in the primary STICH analysis. Those data showed a 5% reduction in all-cause mortality at 6 years with the addition of CABG to medical therapy.

Dr. Bonow replied, "I think viability may be something you look at in some patients, but the point would be that there are other clinical variables, perhaps coronary anatomy, that one would bring into play."

Dr. Steven Bollings, with the Cardiovascular Center at the University of Michigan in Ann Arbor, said the primary STICH results provide a clear answer that patients with heart failure and left ventricular dysfunction benefit from coronary bypass surgery, but that the viability substudy raises a number of questions. He said that myocardial "may not be the No. 1 criterion by which we send patients to the operating room" and that other variables such as whether the patient has clear distal targets or is robust may be more important.

Dr. Gregg W. Stone of Columbia University, New York, said, "While I admit this is the clearly the best and most important viability study ever done, I don’t know that it definitively answers the question for us that viability doesn’t matter."

He pointed out that the viability data were based on only half of the STICH participants, the subsets were unbalanced with 80% of patients having viable myocardium and that some would say it’s not appropriate to look for interaction testing off of a negative end point.

"What I take away from this is that if there’s viability, I really want to be sure to revascularize," said Dr. Ted E. Feldman of NorthShore University HealthSystem in Evanston, Ill. "But prior to seeing these results, I was inclined to say if there wasn’t viability, not to vascularize. And the results of the trial challenge that historic bias," he added.

STICH Viability was supported by grants from the National Heart, Lung, and Blood Institute and Abbott Laboratories. Dr. Bonow had no relevant disclosures.

NEW ORLEANS – Myocardial viability failed to predict a significant survival benefit from coronary bypass surgery in patients with coronary artery disease and left ventricular dysfunction in the STICH Viability substudy.

The data are surprising and call into question the long-standing practice of assessing myocardial viability as a means to predict clinical benefit from coronary bypass surgery.

The substudy included 610 of the 1,212 patients in the Surgical Treatment for Ischemic Heart Failure (STICH) trial who underwent baseline myocardial viability testing using SPECT or dobutamine echocardiography, or both, and were randomly assigned to aggressive medical therapy with or without coronary artery bypass surgery (CABG).

At a median follow-up of 5 years, 51% of patients without viable myocardium and 37% with viable myocardium died. The presence of viable myocardium significantly reduced the risk of all-cause mortality by 36%, but the survival advantage lost statistical significance in a multivariable analysis that included other prognostic variables, Dr. Robert Bonow reported at the annual meeting of the American College of Cardiology.

The secondary outcome of cardiovascular mortality was also significantly lower in patients with myocardial viability compared with those without myocardial viability, at 29% and 43%, respectively, but once again, the association lost significance in multivariable analysis.

Notably, the secondary composite end point of death plus cardiovascular hospitalization, which is commonly used in heart failure trials, retained significance in multivariable analysis in favor of patients with myocardial viability, occurring in 63% of patients with viable myocardium and 82% of those without.

There was no significant interaction, however, between myocardial viability status and medical versus surgical treatment with respect to mortality, whether assessed according to treatment assigned or to the treatment actually received, said Dr. Bonow, professor of cardiology at Northwestern University in Chicago. Five-year all-cause mortality rates among the 114 patients without myocardial viability were 56% with medical therapy and 42% with CABG. Among the 487 patients with myocardial viability the rates were 35% vs. 31%, respectively.

"The lack of interaction between myocardial viability and benefit from CABG in this study indicates that assessment of myocardial viability, independent of other relevant variables, should not be the deciding factor in selecting the best therapy for patients with ischemic left ventricular function," he said.

Discussant Bernard Gersh, professor of medicine at Mayo Clinic in Rochester, Minn., asked what clinicians should analyze to determine which of their patients with heart failure and coronary disease to send to surgery, particularly in light of the benefits observed with CABG in the primary STICH analysis. Those data showed a 5% reduction in all-cause mortality at 6 years with the addition of CABG to medical therapy.

Dr. Bonow replied, "I think viability may be something you look at in some patients, but the point would be that there are other clinical variables, perhaps coronary anatomy, that one would bring into play."

Dr. Steven Bollings, with the Cardiovascular Center at the University of Michigan in Ann Arbor, said the primary STICH results provide a clear answer that patients with heart failure and left ventricular dysfunction benefit from coronary bypass surgery, but that the viability substudy raises a number of questions. He said that myocardial "may not be the No. 1 criterion by which we send patients to the operating room" and that other variables such as whether the patient has clear distal targets or is robust may be more important.

Dr. Gregg W. Stone of Columbia University, New York, said, "While I admit this is the clearly the best and most important viability study ever done, I don’t know that it definitively answers the question for us that viability doesn’t matter."

He pointed out that the viability data were based on only half of the STICH participants, the subsets were unbalanced with 80% of patients having viable myocardium and that some would say it’s not appropriate to look for interaction testing off of a negative end point.

"What I take away from this is that if there’s viability, I really want to be sure to revascularize," said Dr. Ted E. Feldman of NorthShore University HealthSystem in Evanston, Ill. "But prior to seeing these results, I was inclined to say if there wasn’t viability, not to vascularize. And the results of the trial challenge that historic bias," he added.

STICH Viability was supported by grants from the National Heart, Lung, and Blood Institute and Abbott Laboratories. Dr. Bonow had no relevant disclosures.

NEW ORLEANS – Myocardial viability failed to predict a significant survival benefit from coronary bypass surgery in patients with coronary artery disease and left ventricular dysfunction in the STICH Viability substudy.

The data are surprising and call into question the long-standing practice of assessing myocardial viability as a means to predict clinical benefit from coronary bypass surgery.

The substudy included 610 of the 1,212 patients in the Surgical Treatment for Ischemic Heart Failure (STICH) trial who underwent baseline myocardial viability testing using SPECT or dobutamine echocardiography, or both, and were randomly assigned to aggressive medical therapy with or without coronary artery bypass surgery (CABG).

At a median follow-up of 5 years, 51% of patients without viable myocardium and 37% with viable myocardium died. The presence of viable myocardium significantly reduced the risk of all-cause mortality by 36%, but the survival advantage lost statistical significance in a multivariable analysis that included other prognostic variables, Dr. Robert Bonow reported at the annual meeting of the American College of Cardiology.

The secondary outcome of cardiovascular mortality was also significantly lower in patients with myocardial viability compared with those without myocardial viability, at 29% and 43%, respectively, but once again, the association lost significance in multivariable analysis.

Notably, the secondary composite end point of death plus cardiovascular hospitalization, which is commonly used in heart failure trials, retained significance in multivariable analysis in favor of patients with myocardial viability, occurring in 63% of patients with viable myocardium and 82% of those without.

There was no significant interaction, however, between myocardial viability status and medical versus surgical treatment with respect to mortality, whether assessed according to treatment assigned or to the treatment actually received, said Dr. Bonow, professor of cardiology at Northwestern University in Chicago. Five-year all-cause mortality rates among the 114 patients without myocardial viability were 56% with medical therapy and 42% with CABG. Among the 487 patients with myocardial viability the rates were 35% vs. 31%, respectively.

"The lack of interaction between myocardial viability and benefit from CABG in this study indicates that assessment of myocardial viability, independent of other relevant variables, should not be the deciding factor in selecting the best therapy for patients with ischemic left ventricular function," he said.

Discussant Bernard Gersh, professor of medicine at Mayo Clinic in Rochester, Minn., asked what clinicians should analyze to determine which of their patients with heart failure and coronary disease to send to surgery, particularly in light of the benefits observed with CABG in the primary STICH analysis. Those data showed a 5% reduction in all-cause mortality at 6 years with the addition of CABG to medical therapy.

Dr. Bonow replied, "I think viability may be something you look at in some patients, but the point would be that there are other clinical variables, perhaps coronary anatomy, that one would bring into play."

Dr. Steven Bollings, with the Cardiovascular Center at the University of Michigan in Ann Arbor, said the primary STICH results provide a clear answer that patients with heart failure and left ventricular dysfunction benefit from coronary bypass surgery, but that the viability substudy raises a number of questions. He said that myocardial "may not be the No. 1 criterion by which we send patients to the operating room" and that other variables such as whether the patient has clear distal targets or is robust may be more important.

Dr. Gregg W. Stone of Columbia University, New York, said, "While I admit this is the clearly the best and most important viability study ever done, I don’t know that it definitively answers the question for us that viability doesn’t matter."

He pointed out that the viability data were based on only half of the STICH participants, the subsets were unbalanced with 80% of patients having viable myocardium and that some would say it’s not appropriate to look for interaction testing off of a negative end point.

"What I take away from this is that if there’s viability, I really want to be sure to revascularize," said Dr. Ted E. Feldman of NorthShore University HealthSystem in Evanston, Ill. "But prior to seeing these results, I was inclined to say if there wasn’t viability, not to vascularize. And the results of the trial challenge that historic bias," he added.

STICH Viability was supported by grants from the National Heart, Lung, and Blood Institute and Abbott Laboratories. Dr. Bonow had no relevant disclosures.

NEW ORLEANS – The investigational agent delcasertib failed to reduce myocardial infarct size or improve clinical outcomes when given during percutaneous coronary intervention for acute MI in the phase IIb PROTECTION AMI trial.

Delcasertib is a highly selective inhibitor of delta protein kinase C, which has been implicated in mitochondrial injury during ischemic reperfusion injury and apoptosis or necrosis. Based on a previous study showing delcasertib reduced biomarkers of infarct size, "we had expected a 20% reduction in infarct size, and we did not observe that across all dosages," lead author Dr. A. Michael Lincoff said in presenting the results of the phase IIb PROTECTION AMI trial at the annual meeting of the American College of Cardiology.

During a panel discussion of the findings, Dr. Sanjay Kaul of Cedars Sinai Medical Center, Los Angeles, said delcasertib joins a long list of treatments targeting reperfusion injury where the promise of cardioprotection seen in experimental models has not translated into clinical trial evidence.

"Congratulations, Dr. Lincoff, on a well-performed and well-presented study, but unfortunately, another one bites the dust," he said.

Dr. Kaul said there are critical differences between animal models and humans – most notably that the timing of ischemia in humans is uncertain – and he asked whether the treatment was given too late, the dose was incorrect, and the intravenous route of administration was appropriate.

Dr. Lincoff replied that the lack of virtually any side effects associated with delcasertib, previously known as KAI-9803, allowed them to use very high doses that were shown to provide blood and tissue levels similar to those observed with intracoronary administration. Animal studies were also performed comparing intravenous with intracoronary administration and the effect was the same, even when delcasertib was administered after the ischemia had started. Typically, the drug was on board 17 minutes before PCI began.

Based on the results, Bristol-Myers Squibb has decided not to continue development of delcasertib, although study cosponsor KAI Pharmaceuticals has continued interest in evaluating the drug for such indications as stroke, coronary bypass surgery and kidney damage, said Dr. Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research.

The phase IIb PROTECTION AMI analysis included 1,176 patients with acute ST-segment elevation myocardial infarction (STEMI), cardiac ischemia for at least 30 minutes, arriving for PCI within 6 hours of symptom onset and randomly assigned them to placebo or delcasertib IV infusion at 50 mg per hour, 150 mg/hour or 450 mg/hour immediately before PCI.

Among 911 evaluable anterior STEMI patients, there was no significant difference in the primary end point of infarct size as assessed by creatine kinase-MB area under the curve (AUC) between the placebo arm (6,471 ng-hr/mL) and delcasertib at the 50-mg dose (5,917 ng-hr/mL), the 150-mg dose (5,650 ng-hr/mL) or 450-mg dose (6,204 ng-hr/mL), Dr. Lincoff said.

ST segment recovery AUC on 24-hour ECG monitoring was also similar at 8,377 microvolt per minute, 7,707 microV-min., 7,779 microV-min. and 8,188 microV-min., respectively.

At 3-month follow-up, 8.6% of placebo-treated patients had a left ventricular ejection fraction of 30% or more compared with 5.1% treated with 50 mg delcasertib, 7.3% with 150 mg and 9.0% with 450 mg. Outcomes were also similar among 156 patients with inferior STEMI.

Recognizing that some patients may have arrived at the PCI lab and received delcasertib after already experiencing reperfusion injury, the researchers evaluated a prospectively defined subgroup of anterior MI patients based on pre-PCI TIMI (Thrombolysis in Myocardial Infarction) scores. Among these patients, there was a soft trend toward improved CK-MB AUC with delcasertib in patients with occluded TIMI flow (score 0/1), suggesting there may be some biological activity with the agent, Dr. Lincoff said. CK-MB AUC was 8,013 ng-hr/mL with placebo, 7,232 ng-hr/mL with delcasertib 50 mg, 6,872 ng-hr/mL with 150 mg, and 6,879 ng-hr/mL with 450 mg.

PROTECTION AMI was supported by Bristol-Myers Squibb and KAI Pharmaceuticals. Dr. Lincoff reported research funding and travel reimbursement from KAI and Bristol-Myers Squibb and has been an advisor to Bristol-Myers Squibb.

NEW ORLEANS – The investigational agent delcasertib failed to reduce myocardial infarct size or improve clinical outcomes when given during percutaneous coronary intervention for acute MI in the phase IIb PROTECTION AMI trial.

Delcasertib is a highly selective inhibitor of delta protein kinase C, which has been implicated in mitochondrial injury during ischemic reperfusion injury and apoptosis or necrosis. Based on a previous study showing delcasertib reduced biomarkers of infarct size, "we had expected a 20% reduction in infarct size, and we did not observe that across all dosages," lead author Dr. A. Michael Lincoff said in presenting the results of the phase IIb PROTECTION AMI trial at the annual meeting of the American College of Cardiology.

During a panel discussion of the findings, Dr. Sanjay Kaul of Cedars Sinai Medical Center, Los Angeles, said delcasertib joins a long list of treatments targeting reperfusion injury where the promise of cardioprotection seen in experimental models has not translated into clinical trial evidence.

"Congratulations, Dr. Lincoff, on a well-performed and well-presented study, but unfortunately, another one bites the dust," he said.

Dr. Kaul said there are critical differences between animal models and humans – most notably that the timing of ischemia in humans is uncertain – and he asked whether the treatment was given too late, the dose was incorrect, and the intravenous route of administration was appropriate.

Dr. Lincoff replied that the lack of virtually any side effects associated with delcasertib, previously known as KAI-9803, allowed them to use very high doses that were shown to provide blood and tissue levels similar to those observed with intracoronary administration. Animal studies were also performed comparing intravenous with intracoronary administration and the effect was the same, even when delcasertib was administered after the ischemia had started. Typically, the drug was on board 17 minutes before PCI began.

Based on the results, Bristol-Myers Squibb has decided not to continue development of delcasertib, although study cosponsor KAI Pharmaceuticals has continued interest in evaluating the drug for such indications as stroke, coronary bypass surgery and kidney damage, said Dr. Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research.

The phase IIb PROTECTION AMI analysis included 1,176 patients with acute ST-segment elevation myocardial infarction (STEMI), cardiac ischemia for at least 30 minutes, arriving for PCI within 6 hours of symptom onset and randomly assigned them to placebo or delcasertib IV infusion at 50 mg per hour, 150 mg/hour or 450 mg/hour immediately before PCI.

Among 911 evaluable anterior STEMI patients, there was no significant difference in the primary end point of infarct size as assessed by creatine kinase-MB area under the curve (AUC) between the placebo arm (6,471 ng-hr/mL) and delcasertib at the 50-mg dose (5,917 ng-hr/mL), the 150-mg dose (5,650 ng-hr/mL) or 450-mg dose (6,204 ng-hr/mL), Dr. Lincoff said.

ST segment recovery AUC on 24-hour ECG monitoring was also similar at 8,377 microvolt per minute, 7,707 microV-min., 7,779 microV-min. and 8,188 microV-min., respectively.

At 3-month follow-up, 8.6% of placebo-treated patients had a left ventricular ejection fraction of 30% or more compared with 5.1% treated with 50 mg delcasertib, 7.3% with 150 mg and 9.0% with 450 mg. Outcomes were also similar among 156 patients with inferior STEMI.

Recognizing that some patients may have arrived at the PCI lab and received delcasertib after already experiencing reperfusion injury, the researchers evaluated a prospectively defined subgroup of anterior MI patients based on pre-PCI TIMI (Thrombolysis in Myocardial Infarction) scores. Among these patients, there was a soft trend toward improved CK-MB AUC with delcasertib in patients with occluded TIMI flow (score 0/1), suggesting there may be some biological activity with the agent, Dr. Lincoff said. CK-MB AUC was 8,013 ng-hr/mL with placebo, 7,232 ng-hr/mL with delcasertib 50 mg, 6,872 ng-hr/mL with 150 mg, and 6,879 ng-hr/mL with 450 mg.

PROTECTION AMI was supported by Bristol-Myers Squibb and KAI Pharmaceuticals. Dr. Lincoff reported research funding and travel reimbursement from KAI and Bristol-Myers Squibb and has been an advisor to Bristol-Myers Squibb.

NEW ORLEANS – The investigational agent delcasertib failed to reduce myocardial infarct size or improve clinical outcomes when given during percutaneous coronary intervention for acute MI in the phase IIb PROTECTION AMI trial.

Delcasertib is a highly selective inhibitor of delta protein kinase C, which has been implicated in mitochondrial injury during ischemic reperfusion injury and apoptosis or necrosis. Based on a previous study showing delcasertib reduced biomarkers of infarct size, "we had expected a 20% reduction in infarct size, and we did not observe that across all dosages," lead author Dr. A. Michael Lincoff said in presenting the results of the phase IIb PROTECTION AMI trial at the annual meeting of the American College of Cardiology.

During a panel discussion of the findings, Dr. Sanjay Kaul of Cedars Sinai Medical Center, Los Angeles, said delcasertib joins a long list of treatments targeting reperfusion injury where the promise of cardioprotection seen in experimental models has not translated into clinical trial evidence.

"Congratulations, Dr. Lincoff, on a well-performed and well-presented study, but unfortunately, another one bites the dust," he said.

Dr. Kaul said there are critical differences between animal models and humans – most notably that the timing of ischemia in humans is uncertain – and he asked whether the treatment was given too late, the dose was incorrect, and the intravenous route of administration was appropriate.

Dr. Lincoff replied that the lack of virtually any side effects associated with delcasertib, previously known as KAI-9803, allowed them to use very high doses that were shown to provide blood and tissue levels similar to those observed with intracoronary administration. Animal studies were also performed comparing intravenous with intracoronary administration and the effect was the same, even when delcasertib was administered after the ischemia had started. Typically, the drug was on board 17 minutes before PCI began.

Based on the results, Bristol-Myers Squibb has decided not to continue development of delcasertib, although study cosponsor KAI Pharmaceuticals has continued interest in evaluating the drug for such indications as stroke, coronary bypass surgery and kidney damage, said Dr. Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research.

The phase IIb PROTECTION AMI analysis included 1,176 patients with acute ST-segment elevation myocardial infarction (STEMI), cardiac ischemia for at least 30 minutes, arriving for PCI within 6 hours of symptom onset and randomly assigned them to placebo or delcasertib IV infusion at 50 mg per hour, 150 mg/hour or 450 mg/hour immediately before PCI.

Among 911 evaluable anterior STEMI patients, there was no significant difference in the primary end point of infarct size as assessed by creatine kinase-MB area under the curve (AUC) between the placebo arm (6,471 ng-hr/mL) and delcasertib at the 50-mg dose (5,917 ng-hr/mL), the 150-mg dose (5,650 ng-hr/mL) or 450-mg dose (6,204 ng-hr/mL), Dr. Lincoff said.

ST segment recovery AUC on 24-hour ECG monitoring was also similar at 8,377 microvolt per minute, 7,707 microV-min., 7,779 microV-min. and 8,188 microV-min., respectively.

At 3-month follow-up, 8.6% of placebo-treated patients had a left ventricular ejection fraction of 30% or more compared with 5.1% treated with 50 mg delcasertib, 7.3% with 150 mg and 9.0% with 450 mg. Outcomes were also similar among 156 patients with inferior STEMI.

Recognizing that some patients may have arrived at the PCI lab and received delcasertib after already experiencing reperfusion injury, the researchers evaluated a prospectively defined subgroup of anterior MI patients based on pre-PCI TIMI (Thrombolysis in Myocardial Infarction) scores. Among these patients, there was a soft trend toward improved CK-MB AUC with delcasertib in patients with occluded TIMI flow (score 0/1), suggesting there may be some biological activity with the agent, Dr. Lincoff said. CK-MB AUC was 8,013 ng-hr/mL with placebo, 7,232 ng-hr/mL with delcasertib 50 mg, 6,872 ng-hr/mL with 150 mg, and 6,879 ng-hr/mL with 450 mg.

PROTECTION AMI was supported by Bristol-Myers Squibb and KAI Pharmaceuticals. Dr. Lincoff reported research funding and travel reimbursement from KAI and Bristol-Myers Squibb and has been an advisor to Bristol-Myers Squibb.

NEW ORLEANS – The investigational agent delcasertib failed to reduce myocardial infarct size or improve clinical outcomes when given during percutaneous coronary intervention for acute MI in the phase IIb PROTECTION AMI trial.

Delcasertib is a highly selective inhibitor of delta protein kinase C, which has been implicated in mitochondrial injury during ischemic reperfusion injury and apoptosis or necrosis. Based on a previous study showing delcasertib reduced biomarkers of infarct size, "we had expected a 20% reduction in infarct size, and we did not observe that across all dosages," lead author Dr. A. Michael Lincoff said in presenting the results of the phase IIb PROTECTION AMI trial at the annual meeting of the American College of Cardiology.

During a panel discussion of the findings, Dr. Sanjay Kaul of Cedars Sinai Medical Center, Los Angeles, said delcasertib joins a long list of treatments targeting reperfusion injury where the promise of cardioprotection seen in experimental models has not translated into clinical trial evidence.

"Congratulations, Dr. Lincoff, on a well-performed and well-presented study, but unfortunately, another one bites the dust," he said.

Dr. Kaul said there are critical differences between animal models and humans – most notably that the timing of ischemia in humans is uncertain – and he asked whether the treatment was given too late, the dose was incorrect, and the intravenous route of administration was appropriate.

Dr. Lincoff replied that the lack of virtually any side effects associated with delcasertib, previously known as KAI-9803, allowed them to use very high doses that were shown to provide blood and tissue levels similar to those observed with intracoronary administration. Animal studies were also performed comparing intravenous with intracoronary administration and the effect was the same, even when delcasertib was administered after the ischemia had started. Typically, the drug was on board 17 minutes before PCI began.

Based on the results, Bristol-Myers Squibb has decided not to continue development of delcasertib, although study cosponsor KAI Pharmaceuticals has continued interest in evaluating the drug for such indications as stroke, coronary bypass surgery and kidney damage, said Dr. Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research.

The phase IIb PROTECTION AMI analysis included 1,176 patients with acute ST-segment elevation myocardial infarction (STEMI), cardiac ischemia for at least 30 minutes, arriving for PCI within 6 hours of symptom onset and randomly assigned them to placebo or delcasertib IV infusion at 50 mg per hour, 150 mg/hour or 450 mg/hour immediately before PCI.

Among 911 evaluable anterior STEMI patients, there was no significant difference in the primary end point of infarct size as assessed by creatine kinase-MB area under the curve (AUC) between the placebo arm (6,471 ng-hr/mL) and delcasertib at the 50-mg dose (5,917 ng-hr/mL), the 150-mg dose (5,650 ng-hr/mL) or 450-mg dose (6,204 ng-hr/mL), Dr. Lincoff said.

ST segment recovery AUC on 24-hour ECG monitoring was also similar at 8,377 microvolt per minute, 7,707 microV-min., 7,779 microV-min. and 8,188 microV-min., respectively.

At 3-month follow-up, 8.6% of placebo-treated patients had a left ventricular ejection fraction of 30% or more compared with 5.1% treated with 50 mg delcasertib, 7.3% with 150 mg and 9.0% with 450 mg. Outcomes were also similar among 156 patients with inferior STEMI.

Recognizing that some patients may have arrived at the PCI lab and received delcasertib after already experiencing reperfusion injury, the researchers evaluated a prospectively defined subgroup of anterior MI patients based on pre-PCI TIMI (Thrombolysis in Myocardial Infarction) scores. Among these patients, there was a soft trend toward improved CK-MB AUC with delcasertib in patients with occluded TIMI flow (score 0/1), suggesting there may be some biological activity with the agent, Dr. Lincoff said. CK-MB AUC was 8,013 ng-hr/mL with placebo, 7,232 ng-hr/mL with delcasertib 50 mg, 6,872 ng-hr/mL with 150 mg, and 6,879 ng-hr/mL with 450 mg.

PROTECTION AMI was supported by Bristol-Myers Squibb and KAI Pharmaceuticals. Dr. Lincoff reported research funding and travel reimbursement from KAI and Bristol-Myers Squibb and has been an advisor to Bristol-Myers Squibb.

NEW ORLEANS – The investigational agent delcasertib failed to reduce myocardial infarct size or improve clinical outcomes when given during percutaneous coronary intervention for acute MI in the phase IIb PROTECTION AMI trial.

Delcasertib is a highly selective inhibitor of delta protein kinase C, which has been implicated in mitochondrial injury during ischemic reperfusion injury and apoptosis or necrosis. Based on a previous study showing delcasertib reduced biomarkers of infarct size, "we had expected a 20% reduction in infarct size, and we did not observe that across all dosages," lead author Dr. A. Michael Lincoff said in presenting the results of the phase IIb PROTECTION AMI trial at the annual meeting of the American College of Cardiology.

During a panel discussion of the findings, Dr. Sanjay Kaul of Cedars Sinai Medical Center, Los Angeles, said delcasertib joins a long list of treatments targeting reperfusion injury where the promise of cardioprotection seen in experimental models has not translated into clinical trial evidence.

"Congratulations, Dr. Lincoff, on a well-performed and well-presented study, but unfortunately, another one bites the dust," he said.

Dr. Kaul said there are critical differences between animal models and humans – most notably that the timing of ischemia in humans is uncertain – and he asked whether the treatment was given too late, the dose was incorrect, and the intravenous route of administration was appropriate.

Dr. Lincoff replied that the lack of virtually any side effects associated with delcasertib, previously known as KAI-9803, allowed them to use very high doses that were shown to provide blood and tissue levels similar to those observed with intracoronary administration. Animal studies were also performed comparing intravenous with intracoronary administration and the effect was the same, even when delcasertib was administered after the ischemia had started. Typically, the drug was on board 17 minutes before PCI began.

Based on the results, Bristol-Myers Squibb has decided not to continue development of delcasertib, although study cosponsor KAI Pharmaceuticals has continued interest in evaluating the drug for such indications as stroke, coronary bypass surgery and kidney damage, said Dr. Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research.

The phase IIb PROTECTION AMI analysis included 1,176 patients with acute ST-segment elevation myocardial infarction (STEMI), cardiac ischemia for at least 30 minutes, arriving for PCI within 6 hours of symptom onset and randomly assigned them to placebo or delcasertib IV infusion at 50 mg per hour, 150 mg/hour or 450 mg/hour immediately before PCI.

Among 911 evaluable anterior STEMI patients, there was no significant difference in the primary end point of infarct size as assessed by creatine kinase-MB area under the curve (AUC) between the placebo arm (6,471 ng-hr/mL) and delcasertib at the 50-mg dose (5,917 ng-hr/mL), the 150-mg dose (5,650 ng-hr/mL) or 450-mg dose (6,204 ng-hr/mL), Dr. Lincoff said.

ST segment recovery AUC on 24-hour ECG monitoring was also similar at 8,377 microvolt per minute, 7,707 microV-min., 7,779 microV-min. and 8,188 microV-min., respectively.

At 3-month follow-up, 8.6% of placebo-treated patients had a left ventricular ejection fraction of 30% or more compared with 5.1% treated with 50 mg delcasertib, 7.3% with 150 mg and 9.0% with 450 mg. Outcomes were also similar among 156 patients with inferior STEMI.

Recognizing that some patients may have arrived at the PCI lab and received delcasertib after already experiencing reperfusion injury, the researchers evaluated a prospectively defined subgroup of anterior MI patients based on pre-PCI TIMI (Thrombolysis in Myocardial Infarction) scores. Among these patients, there was a soft trend toward improved CK-MB AUC with delcasertib in patients with occluded TIMI flow (score 0/1), suggesting there may be some biological activity with the agent, Dr. Lincoff said. CK-MB AUC was 8,013 ng-hr/mL with placebo, 7,232 ng-hr/mL with delcasertib 50 mg, 6,872 ng-hr/mL with 150 mg, and 6,879 ng-hr/mL with 450 mg.

PROTECTION AMI was supported by Bristol-Myers Squibb and KAI Pharmaceuticals. Dr. Lincoff reported research funding and travel reimbursement from KAI and Bristol-Myers Squibb and has been an advisor to Bristol-Myers Squibb.

NEW ORLEANS – The investigational agent delcasertib failed to reduce myocardial infarct size or improve clinical outcomes when given during percutaneous coronary intervention for acute MI in the phase IIb PROTECTION AMI trial.

Delcasertib is a highly selective inhibitor of delta protein kinase C, which has been implicated in mitochondrial injury during ischemic reperfusion injury and apoptosis or necrosis. Based on a previous study showing delcasertib reduced biomarkers of infarct size, "we had expected a 20% reduction in infarct size, and we did not observe that across all dosages," lead author Dr. A. Michael Lincoff said in presenting the results of the phase IIb PROTECTION AMI trial at the annual meeting of the American College of Cardiology.

During a panel discussion of the findings, Dr. Sanjay Kaul of Cedars Sinai Medical Center, Los Angeles, said delcasertib joins a long list of treatments targeting reperfusion injury where the promise of cardioprotection seen in experimental models has not translated into clinical trial evidence.

"Congratulations, Dr. Lincoff, on a well-performed and well-presented study, but unfortunately, another one bites the dust," he said.

Dr. Kaul said there are critical differences between animal models and humans – most notably that the timing of ischemia in humans is uncertain – and he asked whether the treatment was given too late, the dose was incorrect, and the intravenous route of administration was appropriate.

Dr. Lincoff replied that the lack of virtually any side effects associated with delcasertib, previously known as KAI-9803, allowed them to use very high doses that were shown to provide blood and tissue levels similar to those observed with intracoronary administration. Animal studies were also performed comparing intravenous with intracoronary administration and the effect was the same, even when delcasertib was administered after the ischemia had started. Typically, the drug was on board 17 minutes before PCI began.

Based on the results, Bristol-Myers Squibb has decided not to continue development of delcasertib, although study cosponsor KAI Pharmaceuticals has continued interest in evaluating the drug for such indications as stroke, coronary bypass surgery and kidney damage, said Dr. Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research.

The phase IIb PROTECTION AMI analysis included 1,176 patients with acute ST-segment elevation myocardial infarction (STEMI), cardiac ischemia for at least 30 minutes, arriving for PCI within 6 hours of symptom onset and randomly assigned them to placebo or delcasertib IV infusion at 50 mg per hour, 150 mg/hour or 450 mg/hour immediately before PCI.

Among 911 evaluable anterior STEMI patients, there was no significant difference in the primary end point of infarct size as assessed by creatine kinase-MB area under the curve (AUC) between the placebo arm (6,471 ng-hr/mL) and delcasertib at the 50-mg dose (5,917 ng-hr/mL), the 150-mg dose (5,650 ng-hr/mL) or 450-mg dose (6,204 ng-hr/mL), Dr. Lincoff said.

ST segment recovery AUC on 24-hour ECG monitoring was also similar at 8,377 microvolt per minute, 7,707 microV-min., 7,779 microV-min. and 8,188 microV-min., respectively.

At 3-month follow-up, 8.6% of placebo-treated patients had a left ventricular ejection fraction of 30% or more compared with 5.1% treated with 50 mg delcasertib, 7.3% with 150 mg and 9.0% with 450 mg. Outcomes were also similar among 156 patients with inferior STEMI.

Recognizing that some patients may have arrived at the PCI lab and received delcasertib after already experiencing reperfusion injury, the researchers evaluated a prospectively defined subgroup of anterior MI patients based on pre-PCI TIMI (Thrombolysis in Myocardial Infarction) scores. Among these patients, there was a soft trend toward improved CK-MB AUC with delcasertib in patients with occluded TIMI flow (score 0/1), suggesting there may be some biological activity with the agent, Dr. Lincoff said. CK-MB AUC was 8,013 ng-hr/mL with placebo, 7,232 ng-hr/mL with delcasertib 50 mg, 6,872 ng-hr/mL with 150 mg, and 6,879 ng-hr/mL with 450 mg.

PROTECTION AMI was supported by Bristol-Myers Squibb and KAI Pharmaceuticals. Dr. Lincoff reported research funding and travel reimbursement from KAI and Bristol-Myers Squibb and has been an advisor to Bristol-Myers Squibb.

NEW ORLEANS – The investigational agent delcasertib failed to reduce myocardial infarct size or improve clinical outcomes when given during percutaneous coronary intervention for acute MI in the phase IIb PROTECTION AMI trial.

Delcasertib is a highly selective inhibitor of delta protein kinase C, which has been implicated in mitochondrial injury during ischemic reperfusion injury and apoptosis or necrosis. Based on a previous study showing delcasertib reduced biomarkers of infarct size, "we had expected a 20% reduction in infarct size, and we did not observe that across all dosages," lead author Dr. A. Michael Lincoff said in presenting the results of the phase IIb PROTECTION AMI trial at the annual meeting of the American College of Cardiology.

During a panel discussion of the findings, Dr. Sanjay Kaul of Cedars Sinai Medical Center, Los Angeles, said delcasertib joins a long list of treatments targeting reperfusion injury where the promise of cardioprotection seen in experimental models has not translated into clinical trial evidence.

"Congratulations, Dr. Lincoff, on a well-performed and well-presented study, but unfortunately, another one bites the dust," he said.

Dr. Kaul said there are critical differences between animal models and humans – most notably that the timing of ischemia in humans is uncertain – and he asked whether the treatment was given too late, the dose was incorrect, and the intravenous route of administration was appropriate.

Dr. Lincoff replied that the lack of virtually any side effects associated with delcasertib, previously known as KAI-9803, allowed them to use very high doses that were shown to provide blood and tissue levels similar to those observed with intracoronary administration. Animal studies were also performed comparing intravenous with intracoronary administration and the effect was the same, even when delcasertib was administered after the ischemia had started. Typically, the drug was on board 17 minutes before PCI began.

Based on the results, Bristol-Myers Squibb has decided not to continue development of delcasertib, although study cosponsor KAI Pharmaceuticals has continued interest in evaluating the drug for such indications as stroke, coronary bypass surgery and kidney damage, said Dr. Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research.

The phase IIb PROTECTION AMI analysis included 1,176 patients with acute ST-segment elevation myocardial infarction (STEMI), cardiac ischemia for at least 30 minutes, arriving for PCI within 6 hours of symptom onset and randomly assigned them to placebo or delcasertib IV infusion at 50 mg per hour, 150 mg/hour or 450 mg/hour immediately before PCI.

Among 911 evaluable anterior STEMI patients, there was no significant difference in the primary end point of infarct size as assessed by creatine kinase-MB area under the curve (AUC) between the placebo arm (6,471 ng-hr/mL) and delcasertib at the 50-mg dose (5,917 ng-hr/mL), the 150-mg dose (5,650 ng-hr/mL) or 450-mg dose (6,204 ng-hr/mL), Dr. Lincoff said.

ST segment recovery AUC on 24-hour ECG monitoring was also similar at 8,377 microvolt per minute, 7,707 microV-min., 7,779 microV-min. and 8,188 microV-min., respectively.

At 3-month follow-up, 8.6% of placebo-treated patients had a left ventricular ejection fraction of 30% or more compared with 5.1% treated with 50 mg delcasertib, 7.3% with 150 mg and 9.0% with 450 mg. Outcomes were also similar among 156 patients with inferior STEMI.

Recognizing that some patients may have arrived at the PCI lab and received delcasertib after already experiencing reperfusion injury, the researchers evaluated a prospectively defined subgroup of anterior MI patients based on pre-PCI TIMI (Thrombolysis in Myocardial Infarction) scores. Among these patients, there was a soft trend toward improved CK-MB AUC with delcasertib in patients with occluded TIMI flow (score 0/1), suggesting there may be some biological activity with the agent, Dr. Lincoff said. CK-MB AUC was 8,013 ng-hr/mL with placebo, 7,232 ng-hr/mL with delcasertib 50 mg, 6,872 ng-hr/mL with 150 mg, and 6,879 ng-hr/mL with 450 mg.

PROTECTION AMI was supported by Bristol-Myers Squibb and KAI Pharmaceuticals. Dr. Lincoff reported research funding and travel reimbursement from KAI and Bristol-Myers Squibb and has been an advisor to Bristol-Myers Squibb.

NEW ORLEANS – The investigational agent delcasertib failed to reduce myocardial infarct size or improve clinical outcomes when given during percutaneous coronary intervention for acute MI in the phase IIb PROTECTION AMI trial.

Delcasertib is a highly selective inhibitor of delta protein kinase C, which has been implicated in mitochondrial injury during ischemic reperfusion injury and apoptosis or necrosis. Based on a previous study showing delcasertib reduced biomarkers of infarct size, "we had expected a 20% reduction in infarct size, and we did not observe that across all dosages," lead author Dr. A. Michael Lincoff said in presenting the results of the phase IIb PROTECTION AMI trial at the annual meeting of the American College of Cardiology.

During a panel discussion of the findings, Dr. Sanjay Kaul of Cedars Sinai Medical Center, Los Angeles, said delcasertib joins a long list of treatments targeting reperfusion injury where the promise of cardioprotection seen in experimental models has not translated into clinical trial evidence.

"Congratulations, Dr. Lincoff, on a well-performed and well-presented study, but unfortunately, another one bites the dust," he said.

Dr. Kaul said there are critical differences between animal models and humans – most notably that the timing of ischemia in humans is uncertain – and he asked whether the treatment was given too late, the dose was incorrect, and the intravenous route of administration was appropriate.

Dr. Lincoff replied that the lack of virtually any side effects associated with delcasertib, previously known as KAI-9803, allowed them to use very high doses that were shown to provide blood and tissue levels similar to those observed with intracoronary administration. Animal studies were also performed comparing intravenous with intracoronary administration and the effect was the same, even when delcasertib was administered after the ischemia had started. Typically, the drug was on board 17 minutes before PCI began.

Based on the results, Bristol-Myers Squibb has decided not to continue development of delcasertib, although study cosponsor KAI Pharmaceuticals has continued interest in evaluating the drug for such indications as stroke, coronary bypass surgery and kidney damage, said Dr. Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research.

The phase IIb PROTECTION AMI analysis included 1,176 patients with acute ST-segment elevation myocardial infarction (STEMI), cardiac ischemia for at least 30 minutes, arriving for PCI within 6 hours of symptom onset and randomly assigned them to placebo or delcasertib IV infusion at 50 mg per hour, 150 mg/hour or 450 mg/hour immediately before PCI.

Among 911 evaluable anterior STEMI patients, there was no significant difference in the primary end point of infarct size as assessed by creatine kinase-MB area under the curve (AUC) between the placebo arm (6,471 ng-hr/mL) and delcasertib at the 50-mg dose (5,917 ng-hr/mL), the 150-mg dose (5,650 ng-hr/mL) or 450-mg dose (6,204 ng-hr/mL), Dr. Lincoff said.

ST segment recovery AUC on 24-hour ECG monitoring was also similar at 8,377 microvolt per minute, 7,707 microV-min., 7,779 microV-min. and 8,188 microV-min., respectively.

At 3-month follow-up, 8.6% of placebo-treated patients had a left ventricular ejection fraction of 30% or more compared with 5.1% treated with 50 mg delcasertib, 7.3% with 150 mg and 9.0% with 450 mg. Outcomes were also similar among 156 patients with inferior STEMI.

Recognizing that some patients may have arrived at the PCI lab and received delcasertib after already experiencing reperfusion injury, the researchers evaluated a prospectively defined subgroup of anterior MI patients based on pre-PCI TIMI (Thrombolysis in Myocardial Infarction) scores. Among these patients, there was a soft trend toward improved CK-MB AUC with delcasertib in patients with occluded TIMI flow (score 0/1), suggesting there may be some biological activity with the agent, Dr. Lincoff said. CK-MB AUC was 8,013 ng-hr/mL with placebo, 7,232 ng-hr/mL with delcasertib 50 mg, 6,872 ng-hr/mL with 150 mg, and 6,879 ng-hr/mL with 450 mg.

PROTECTION AMI was supported by Bristol-Myers Squibb and KAI Pharmaceuticals. Dr. Lincoff reported research funding and travel reimbursement from KAI and Bristol-Myers Squibb and has been an advisor to Bristol-Myers Squibb.

NEW ORLEANS – The investigational agent delcasertib failed to reduce myocardial infarct size or improve clinical outcomes when given during percutaneous coronary intervention for acute MI in the phase IIb PROTECTION AMI trial.

Delcasertib is a highly selective inhibitor of delta protein kinase C, which has been implicated in mitochondrial injury during ischemic reperfusion injury and apoptosis or necrosis. Based on a previous study showing delcasertib reduced biomarkers of infarct size, "we had expected a 20% reduction in infarct size, and we did not observe that across all dosages," lead author Dr. A. Michael Lincoff said in presenting the results of the phase IIb PROTECTION AMI trial at the annual meeting of the American College of Cardiology.

During a panel discussion of the findings, Dr. Sanjay Kaul of Cedars Sinai Medical Center, Los Angeles, said delcasertib joins a long list of treatments targeting reperfusion injury where the promise of cardioprotection seen in experimental models has not translated into clinical trial evidence.

"Congratulations, Dr. Lincoff, on a well-performed and well-presented study, but unfortunately, another one bites the dust," he said.

Dr. Kaul said there are critical differences between animal models and humans – most notably that the timing of ischemia in humans is uncertain – and he asked whether the treatment was given too late, the dose was incorrect, and the intravenous route of administration was appropriate.

Dr. Lincoff replied that the lack of virtually any side effects associated with delcasertib, previously known as KAI-9803, allowed them to use very high doses that were shown to provide blood and tissue levels similar to those observed with intracoronary administration. Animal studies were also performed comparing intravenous with intracoronary administration and the effect was the same, even when delcasertib was administered after the ischemia had started. Typically, the drug was on board 17 minutes before PCI began.

Based on the results, Bristol-Myers Squibb has decided not to continue development of delcasertib, although study cosponsor KAI Pharmaceuticals has continued interest in evaluating the drug for such indications as stroke, coronary bypass surgery and kidney damage, said Dr. Lincoff, director of the Cleveland Clinic Coordinating Center for Clinical Research.

The phase IIb PROTECTION AMI analysis included 1,176 patients with acute ST-segment elevation myocardial infarction (STEMI), cardiac ischemia for at least 30 minutes, arriving for PCI within 6 hours of symptom onset and randomly assigned them to placebo or delcasertib IV infusion at 50 mg per hour, 150 mg/hour or 450 mg/hour immediately before PCI.

Among 911 evaluable anterior STEMI patients, there was no significant difference in the primary end point of infarct size as assessed by creatine kinase-MB area under the curve (AUC) between the placebo arm (6,471 ng-hr/mL) and delcasertib at the 50-mg dose (5,917 ng-hr/mL), the 150-mg dose (5,650 ng-hr/mL) or 450-mg dose (6,204 ng-hr/mL), Dr. Lincoff said.

ST segment recovery AUC on 24-hour ECG monitoring was also similar at 8,377 microvolt per minute, 7,707 microV-min., 7,779 microV-min. and 8,188 microV-min., respectively.

At 3-month follow-up, 8.6% of placebo-treated patients had a left ventricular ejection fraction of 30% or more compared with 5.1% treated with 50 mg delcasertib, 7.3% with 150 mg and 9.0% with 450 mg. Outcomes were also similar among 156 patients with inferior STEMI.

Recognizing that some patients may have arrived at the PCI lab and received delcasertib after already experiencing reperfusion injury, the researchers evaluated a prospectively defined subgroup of anterior MI patients based on pre-PCI TIMI (Thrombolysis in Myocardial Infarction) scores. Among these patients, there was a soft trend toward improved CK-MB AUC with delcasertib in patients with occluded TIMI flow (score 0/1), suggesting there may be some biological activity with the agent, Dr. Lincoff said. CK-MB AUC was 8,013 ng-hr/mL with placebo, 7,232 ng-hr/mL with delcasertib 50 mg, 6,872 ng-hr/mL with 150 mg, and 6,879 ng-hr/mL with 450 mg.

PROTECTION AMI was supported by Bristol-Myers Squibb and KAI Pharmaceuticals. Dr. Lincoff reported research funding and travel reimbursement from KAI and Bristol-Myers Squibb and has been an advisor to Bristol-Myers Squibb.

NEW ORLEANS – Calcium channel blockers and diuretics are the best drugs for treating hypertension in the elderly because they are the most effective at reducing the risk of what elderly patients fear most: stroke, Dr. Norman M. Kaplan asserted at the annual meeting of the American College of Cardiology.

"Coronary disease remains by far the most common cause of mortality [in the United States], but stroke poses the greatest threat to the elderly, not coronary disease," said Dr. Kaplan, professor of internal medicine at the University of Texas, Dallas.

He presented a state-of-the-art perspective on antihypertensive therapy in the elderly from the unique vantage point of having served as a member of the third, fourth, fifth, and sixth Joint National Committees on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Dr. Kaplan noted that a British meta-analysis of 46 randomized trials comparing each of the five major classes of antihypertensive drugs with any other class showed that all of the classes were similarly effective in preventing both coronary disease events and strokes, with one exception: calcium channel blockers had a significantly greater preventive effect on stroke than other agents. Diuretics showed a trend in the same direction that didn’t reach statistical significance (BMJ 2009;338:b1665 [doi:10.1136/BMJ.b1665]).

More recently, a secondary analysis of the 19,257-subject ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) demonstrated that calcium channel blocker–based antihypertensive therapy was particularly effective against stroke in the population most in need of such protection: the elderly. Although there was no significant difference in strokes between amlodipine- and atenolol-based therapy in patients younger than age 65 years, there was a highly significant 30% relative risk reduction with amlodipine in the over-65 group (J. Hypertens. 2011;29:583-91).

The latest thinking regarding mechanism of benefit is that calcium channel blockers and diuretics are more effective at reducing stroke risk because they decrease within-individual variation in systolic blood pressure, unlike angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, all of which significantly increase it. In a meta-analysis of 389 randomized, controlled trials of antihypertensive therapy, stroke risk proved strongly related to this interindividual variation in blood pressure (Lancet 2010;375:906-15).

In addition to reducing stroke risk, calcium channel blockers may also have a neuroprotective effect. A French study of 378 elderly, nondemented, hypertensive patients with the complaint of memory loss showed that memory scores were significantly better in those on a calcium channel blocker than on any other class of antihypertensive medication (J. Hypertens. 2010;28:2485-93). Although that’s an intriguing finding, this was an observational study and needs confirmation, in Dr. Kaplan’s view.

Elderly hypertensives predominantly have isolated systolic hypertension. Because of the extensive body of evidence showing that such patients have a good response rate to diuretic monotherapy, he recommends using a diuretic as the first-line drug.

"I would start chlorthalidone – now having a resurgence as the diuretic of choice – at 12.5 mg/day, and add a calcium channel blocker if additional therapy is needed to reach 150/70 mm Hg, which I think is a rational goal to aim for in the elderly," he said.

Indeed, although the 7th Joint National Committee calls 140 mm Hg the upper limit of normal systolic blood pressure at all ages, nearly all the randomized trials that have shown a protective value for antihypertensive therapy in the elderly enrolled patients with a baseline systolic pressure in excess of 160 mm Hg, and achieved an on-treatment systolic pressure in the 150s or 160s.

"I do not think the evidence we have to date shows protective value for treatment in patients with a baseline systolic blood pressure below 160 mm Hg. There is evidence to suggest that if we lower the elderly patient’s systolic blood pressure more than 10-15 mm Hg, we may be invoking additional trouble rather than protecting the patient," said Dr. Kaplan.

"These are old people who obviously have atherosclerotic vascular disease, even if they don’t show it. Reduction in diastolic blood pressure to 65 mm Hg or lower may reduce their coronary perfusion – which occurs only during diastole – to a degree that could invoke a cardiovascular catastrophe," he continued.

Other important aspects of treating elderly hypertensive patients include identifying and overcoming postural hypotension, encouraging the consumption of one or two alcoholic drinks per day for the well-documented health benefits, starting a statin, and measuring home blood pressures to ensure that an individual really is being treated adequately, Dr. Kaplan said.

The risks posed by orthostatic hypotension were recently highlighted in a study of 374 unselected ambulatory adults with an average age of 70 years and no known cardiovascular disease or other comorbidities. An orthostatic decrease in systolic blood pressure greater than 20 mm Hg was present 2 minutes after standing in 12% of them. Over roughly 1 year of follow-up, cardiovascular events were 2.4-fold more frequent in that patient subset (Hypertension 2010;56:56-61).

There are no safe and effective medications for the treatment of orthostatic hypotension. Fortunately, this condition generally responds to nondrug measures, including avoidance of fluid-volume depletion, taking up to 2 full minutes to rise from supine to standing in the morning, raising the head of the bed 15 degrees to help maintain a degree of sympathetic nervous system activation during the night, eating a small breakfast, and crossing the legs when feeling unsteady while standing.

Dr. Kaplan disclosed that he is on the speakers bureaus for Pfizer, AstraZeneca, Merck, Novartis, and Bayer.

NEW ORLEANS – Calcium channel blockers and diuretics are the best drugs for treating hypertension in the elderly because they are the most effective at reducing the risk of what elderly patients fear most: stroke, Dr. Norman M. Kaplan asserted at the annual meeting of the American College of Cardiology.

"Coronary disease remains by far the most common cause of mortality [in the United States], but stroke poses the greatest threat to the elderly, not coronary disease," said Dr. Kaplan, professor of internal medicine at the University of Texas, Dallas.

He presented a state-of-the-art perspective on antihypertensive therapy in the elderly from the unique vantage point of having served as a member of the third, fourth, fifth, and sixth Joint National Committees on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Dr. Kaplan noted that a British meta-analysis of 46 randomized trials comparing each of the five major classes of antihypertensive drugs with any other class showed that all of the classes were similarly effective in preventing both coronary disease events and strokes, with one exception: calcium channel blockers had a significantly greater preventive effect on stroke than other agents. Diuretics showed a trend in the same direction that didn’t reach statistical significance (BMJ 2009;338:b1665 [doi:10.1136/BMJ.b1665]).

More recently, a secondary analysis of the 19,257-subject ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) demonstrated that calcium channel blocker–based antihypertensive therapy was particularly effective against stroke in the population most in need of such protection: the elderly. Although there was no significant difference in strokes between amlodipine- and atenolol-based therapy in patients younger than age 65 years, there was a highly significant 30% relative risk reduction with amlodipine in the over-65 group (J. Hypertens. 2011;29:583-91).

The latest thinking regarding mechanism of benefit is that calcium channel blockers and diuretics are more effective at reducing stroke risk because they decrease within-individual variation in systolic blood pressure, unlike angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, all of which significantly increase it. In a meta-analysis of 389 randomized, controlled trials of antihypertensive therapy, stroke risk proved strongly related to this interindividual variation in blood pressure (Lancet 2010;375:906-15).

In addition to reducing stroke risk, calcium channel blockers may also have a neuroprotective effect. A French study of 378 elderly, nondemented, hypertensive patients with the complaint of memory loss showed that memory scores were significantly better in those on a calcium channel blocker than on any other class of antihypertensive medication (J. Hypertens. 2010;28:2485-93). Although that’s an intriguing finding, this was an observational study and needs confirmation, in Dr. Kaplan’s view.

Elderly hypertensives predominantly have isolated systolic hypertension. Because of the extensive body of evidence showing that such patients have a good response rate to diuretic monotherapy, he recommends using a diuretic as the first-line drug.

"I would start chlorthalidone – now having a resurgence as the diuretic of choice – at 12.5 mg/day, and add a calcium channel blocker if additional therapy is needed to reach 150/70 mm Hg, which I think is a rational goal to aim for in the elderly," he said.

Indeed, although the 7th Joint National Committee calls 140 mm Hg the upper limit of normal systolic blood pressure at all ages, nearly all the randomized trials that have shown a protective value for antihypertensive therapy in the elderly enrolled patients with a baseline systolic pressure in excess of 160 mm Hg, and achieved an on-treatment systolic pressure in the 150s or 160s.

"I do not think the evidence we have to date shows protective value for treatment in patients with a baseline systolic blood pressure below 160 mm Hg. There is evidence to suggest that if we lower the elderly patient’s systolic blood pressure more than 10-15 mm Hg, we may be invoking additional trouble rather than protecting the patient," said Dr. Kaplan.

"These are old people who obviously have atherosclerotic vascular disease, even if they don’t show it. Reduction in diastolic blood pressure to 65 mm Hg or lower may reduce their coronary perfusion – which occurs only during diastole – to a degree that could invoke a cardiovascular catastrophe," he continued.

Other important aspects of treating elderly hypertensive patients include identifying and overcoming postural hypotension, encouraging the consumption of one or two alcoholic drinks per day for the well-documented health benefits, starting a statin, and measuring home blood pressures to ensure that an individual really is being treated adequately, Dr. Kaplan said.

The risks posed by orthostatic hypotension were recently highlighted in a study of 374 unselected ambulatory adults with an average age of 70 years and no known cardiovascular disease or other comorbidities. An orthostatic decrease in systolic blood pressure greater than 20 mm Hg was present 2 minutes after standing in 12% of them. Over roughly 1 year of follow-up, cardiovascular events were 2.4-fold more frequent in that patient subset (Hypertension 2010;56:56-61).

There are no safe and effective medications for the treatment of orthostatic hypotension. Fortunately, this condition generally responds to nondrug measures, including avoidance of fluid-volume depletion, taking up to 2 full minutes to rise from supine to standing in the morning, raising the head of the bed 15 degrees to help maintain a degree of sympathetic nervous system activation during the night, eating a small breakfast, and crossing the legs when feeling unsteady while standing.

Dr. Kaplan disclosed that he is on the speakers bureaus for Pfizer, AstraZeneca, Merck, Novartis, and Bayer.

NEW ORLEANS – Calcium channel blockers and diuretics are the best drugs for treating hypertension in the elderly because they are the most effective at reducing the risk of what elderly patients fear most: stroke, Dr. Norman M. Kaplan asserted at the annual meeting of the American College of Cardiology.

"Coronary disease remains by far the most common cause of mortality [in the United States], but stroke poses the greatest threat to the elderly, not coronary disease," said Dr. Kaplan, professor of internal medicine at the University of Texas, Dallas.

He presented a state-of-the-art perspective on antihypertensive therapy in the elderly from the unique vantage point of having served as a member of the third, fourth, fifth, and sixth Joint National Committees on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Dr. Kaplan noted that a British meta-analysis of 46 randomized trials comparing each of the five major classes of antihypertensive drugs with any other class showed that all of the classes were similarly effective in preventing both coronary disease events and strokes, with one exception: calcium channel blockers had a significantly greater preventive effect on stroke than other agents. Diuretics showed a trend in the same direction that didn’t reach statistical significance (BMJ 2009;338:b1665 [doi:10.1136/BMJ.b1665]).

More recently, a secondary analysis of the 19,257-subject ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) demonstrated that calcium channel blocker–based antihypertensive therapy was particularly effective against stroke in the population most in need of such protection: the elderly. Although there was no significant difference in strokes between amlodipine- and atenolol-based therapy in patients younger than age 65 years, there was a highly significant 30% relative risk reduction with amlodipine in the over-65 group (J. Hypertens. 2011;29:583-91).

The latest thinking regarding mechanism of benefit is that calcium channel blockers and diuretics are more effective at reducing stroke risk because they decrease within-individual variation in systolic blood pressure, unlike angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, all of which significantly increase it. In a meta-analysis of 389 randomized, controlled trials of antihypertensive therapy, stroke risk proved strongly related to this interindividual variation in blood pressure (Lancet 2010;375:906-15).

In addition to reducing stroke risk, calcium channel blockers may also have a neuroprotective effect. A French study of 378 elderly, nondemented, hypertensive patients with the complaint of memory loss showed that memory scores were significantly better in those on a calcium channel blocker than on any other class of antihypertensive medication (J. Hypertens. 2010;28:2485-93). Although that’s an intriguing finding, this was an observational study and needs confirmation, in Dr. Kaplan’s view.

Elderly hypertensives predominantly have isolated systolic hypertension. Because of the extensive body of evidence showing that such patients have a good response rate to diuretic monotherapy, he recommends using a diuretic as the first-line drug.

"I would start chlorthalidone – now having a resurgence as the diuretic of choice – at 12.5 mg/day, and add a calcium channel blocker if additional therapy is needed to reach 150/70 mm Hg, which I think is a rational goal to aim for in the elderly," he said.

Indeed, although the 7th Joint National Committee calls 140 mm Hg the upper limit of normal systolic blood pressure at all ages, nearly all the randomized trials that have shown a protective value for antihypertensive therapy in the elderly enrolled patients with a baseline systolic pressure in excess of 160 mm Hg, and achieved an on-treatment systolic pressure in the 150s or 160s.

"I do not think the evidence we have to date shows protective value for treatment in patients with a baseline systolic blood pressure below 160 mm Hg. There is evidence to suggest that if we lower the elderly patient’s systolic blood pressure more than 10-15 mm Hg, we may be invoking additional trouble rather than protecting the patient," said Dr. Kaplan.

"These are old people who obviously have atherosclerotic vascular disease, even if they don’t show it. Reduction in diastolic blood pressure to 65 mm Hg or lower may reduce their coronary perfusion – which occurs only during diastole – to a degree that could invoke a cardiovascular catastrophe," he continued.

Other important aspects of treating elderly hypertensive patients include identifying and overcoming postural hypotension, encouraging the consumption of one or two alcoholic drinks per day for the well-documented health benefits, starting a statin, and measuring home blood pressures to ensure that an individual really is being treated adequately, Dr. Kaplan said.

The risks posed by orthostatic hypotension were recently highlighted in a study of 374 unselected ambulatory adults with an average age of 70 years and no known cardiovascular disease or other comorbidities. An orthostatic decrease in systolic blood pressure greater than 20 mm Hg was present 2 minutes after standing in 12% of them. Over roughly 1 year of follow-up, cardiovascular events were 2.4-fold more frequent in that patient subset (Hypertension 2010;56:56-61).

There are no safe and effective medications for the treatment of orthostatic hypotension. Fortunately, this condition generally responds to nondrug measures, including avoidance of fluid-volume depletion, taking up to 2 full minutes to rise from supine to standing in the morning, raising the head of the bed 15 degrees to help maintain a degree of sympathetic nervous system activation during the night, eating a small breakfast, and crossing the legs when feeling unsteady while standing.

Dr. Kaplan disclosed that he is on the speakers bureaus for Pfizer, AstraZeneca, Merck, Novartis, and Bayer.

NEW ORLEANS – Calcium channel blockers and diuretics are the best drugs for treating hypertension in the elderly because they are the most effective at reducing the risk of what elderly patients fear most: stroke, Dr. Norman M. Kaplan asserted at the annual meeting of the American College of Cardiology.

"Coronary disease remains by far the most common cause of mortality [in the United States], but stroke poses the greatest threat to the elderly, not coronary disease," said Dr. Kaplan, professor of internal medicine at the University of Texas, Dallas.

He presented a state-of-the-art perspective on antihypertensive therapy in the elderly from the unique vantage point of having served as a member of the third, fourth, fifth, and sixth Joint National Committees on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Dr. Kaplan noted that a British meta-analysis of 46 randomized trials comparing each of the five major classes of antihypertensive drugs with any other class showed that all of the classes were similarly effective in preventing both coronary disease events and strokes, with one exception: calcium channel blockers had a significantly greater preventive effect on stroke than other agents. Diuretics showed a trend in the same direction that didn’t reach statistical significance (BMJ 2009;338:b1665 [doi:10.1136/BMJ.b1665]).

More recently, a secondary analysis of the 19,257-subject ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) demonstrated that calcium channel blocker–based antihypertensive therapy was particularly effective against stroke in the population most in need of such protection: the elderly. Although there was no significant difference in strokes between amlodipine- and atenolol-based therapy in patients younger than age 65 years, there was a highly significant 30% relative risk reduction with amlodipine in the over-65 group (J. Hypertens. 2011;29:583-91).

The latest thinking regarding mechanism of benefit is that calcium channel blockers and diuretics are more effective at reducing stroke risk because they decrease within-individual variation in systolic blood pressure, unlike angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, all of which significantly increase it. In a meta-analysis of 389 randomized, controlled trials of antihypertensive therapy, stroke risk proved strongly related to this interindividual variation in blood pressure (Lancet 2010;375:906-15).

In addition to reducing stroke risk, calcium channel blockers may also have a neuroprotective effect. A French study of 378 elderly, nondemented, hypertensive patients with the complaint of memory loss showed that memory scores were significantly better in those on a calcium channel blocker than on any other class of antihypertensive medication (J. Hypertens. 2010;28:2485-93). Although that’s an intriguing finding, this was an observational study and needs confirmation, in Dr. Kaplan’s view.

Elderly hypertensives predominantly have isolated systolic hypertension. Because of the extensive body of evidence showing that such patients have a good response rate to diuretic monotherapy, he recommends using a diuretic as the first-line drug.

"I would start chlorthalidone – now having a resurgence as the diuretic of choice – at 12.5 mg/day, and add a calcium channel blocker if additional therapy is needed to reach 150/70 mm Hg, which I think is a rational goal to aim for in the elderly," he said.

Indeed, although the 7th Joint National Committee calls 140 mm Hg the upper limit of normal systolic blood pressure at all ages, nearly all the randomized trials that have shown a protective value for antihypertensive therapy in the elderly enrolled patients with a baseline systolic pressure in excess of 160 mm Hg, and achieved an on-treatment systolic pressure in the 150s or 160s.

"I do not think the evidence we have to date shows protective value for treatment in patients with a baseline systolic blood pressure below 160 mm Hg. There is evidence to suggest that if we lower the elderly patient’s systolic blood pressure more than 10-15 mm Hg, we may be invoking additional trouble rather than protecting the patient," said Dr. Kaplan.

"These are old people who obviously have atherosclerotic vascular disease, even if they don’t show it. Reduction in diastolic blood pressure to 65 mm Hg or lower may reduce their coronary perfusion – which occurs only during diastole – to a degree that could invoke a cardiovascular catastrophe," he continued.

Other important aspects of treating elderly hypertensive patients include identifying and overcoming postural hypotension, encouraging the consumption of one or two alcoholic drinks per day for the well-documented health benefits, starting a statin, and measuring home blood pressures to ensure that an individual really is being treated adequately, Dr. Kaplan said.

The risks posed by orthostatic hypotension were recently highlighted in a study of 374 unselected ambulatory adults with an average age of 70 years and no known cardiovascular disease or other comorbidities. An orthostatic decrease in systolic blood pressure greater than 20 mm Hg was present 2 minutes after standing in 12% of them. Over roughly 1 year of follow-up, cardiovascular events were 2.4-fold more frequent in that patient subset (Hypertension 2010;56:56-61).

There are no safe and effective medications for the treatment of orthostatic hypotension. Fortunately, this condition generally responds to nondrug measures, including avoidance of fluid-volume depletion, taking up to 2 full minutes to rise from supine to standing in the morning, raising the head of the bed 15 degrees to help maintain a degree of sympathetic nervous system activation during the night, eating a small breakfast, and crossing the legs when feeling unsteady while standing.

Dr. Kaplan disclosed that he is on the speakers bureaus for Pfizer, AstraZeneca, Merck, Novartis, and Bayer.

NEW ORLEANS – Calcium channel blockers and diuretics are the best drugs for treating hypertension in the elderly because they are the most effective at reducing the risk of what elderly patients fear most: stroke, Dr. Norman M. Kaplan asserted at the annual meeting of the American College of Cardiology.

"Coronary disease remains by far the most common cause of mortality [in the United States], but stroke poses the greatest threat to the elderly, not coronary disease," said Dr. Kaplan, professor of internal medicine at the University of Texas, Dallas.

He presented a state-of-the-art perspective on antihypertensive therapy in the elderly from the unique vantage point of having served as a member of the third, fourth, fifth, and sixth Joint National Committees on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Dr. Kaplan noted that a British meta-analysis of 46 randomized trials comparing each of the five major classes of antihypertensive drugs with any other class showed that all of the classes were similarly effective in preventing both coronary disease events and strokes, with one exception: calcium channel blockers had a significantly greater preventive effect on stroke than other agents. Diuretics showed a trend in the same direction that didn’t reach statistical significance (BMJ 2009;338:b1665 [doi:10.1136/BMJ.b1665]).

More recently, a secondary analysis of the 19,257-subject ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) demonstrated that calcium channel blocker–based antihypertensive therapy was particularly effective against stroke in the population most in need of such protection: the elderly. Although there was no significant difference in strokes between amlodipine- and atenolol-based therapy in patients younger than age 65 years, there was a highly significant 30% relative risk reduction with amlodipine in the over-65 group (J. Hypertens. 2011;29:583-91).

The latest thinking regarding mechanism of benefit is that calcium channel blockers and diuretics are more effective at reducing stroke risk because they decrease within-individual variation in systolic blood pressure, unlike angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, all of which significantly increase it. In a meta-analysis of 389 randomized, controlled trials of antihypertensive therapy, stroke risk proved strongly related to this interindividual variation in blood pressure (Lancet 2010;375:906-15).

In addition to reducing stroke risk, calcium channel blockers may also have a neuroprotective effect. A French study of 378 elderly, nondemented, hypertensive patients with the complaint of memory loss showed that memory scores were significantly better in those on a calcium channel blocker than on any other class of antihypertensive medication (J. Hypertens. 2010;28:2485-93). Although that’s an intriguing finding, this was an observational study and needs confirmation, in Dr. Kaplan’s view.

Elderly hypertensives predominantly have isolated systolic hypertension. Because of the extensive body of evidence showing that such patients have a good response rate to diuretic monotherapy, he recommends using a diuretic as the first-line drug.

"I would start chlorthalidone – now having a resurgence as the diuretic of choice – at 12.5 mg/day, and add a calcium channel blocker if additional therapy is needed to reach 150/70 mm Hg, which I think is a rational goal to aim for in the elderly," he said.

Indeed, although the 7th Joint National Committee calls 140 mm Hg the upper limit of normal systolic blood pressure at all ages, nearly all the randomized trials that have shown a protective value for antihypertensive therapy in the elderly enrolled patients with a baseline systolic pressure in excess of 160 mm Hg, and achieved an on-treatment systolic pressure in the 150s or 160s.

"I do not think the evidence we have to date shows protective value for treatment in patients with a baseline systolic blood pressure below 160 mm Hg. There is evidence to suggest that if we lower the elderly patient’s systolic blood pressure more than 10-15 mm Hg, we may be invoking additional trouble rather than protecting the patient," said Dr. Kaplan.

"These are old people who obviously have atherosclerotic vascular disease, even if they don’t show it. Reduction in diastolic blood pressure to 65 mm Hg or lower may reduce their coronary perfusion – which occurs only during diastole – to a degree that could invoke a cardiovascular catastrophe," he continued.

Other important aspects of treating elderly hypertensive patients include identifying and overcoming postural hypotension, encouraging the consumption of one or two alcoholic drinks per day for the well-documented health benefits, starting a statin, and measuring home blood pressures to ensure that an individual really is being treated adequately, Dr. Kaplan said.

The risks posed by orthostatic hypotension were recently highlighted in a study of 374 unselected ambulatory adults with an average age of 70 years and no known cardiovascular disease or other comorbidities. An orthostatic decrease in systolic blood pressure greater than 20 mm Hg was present 2 minutes after standing in 12% of them. Over roughly 1 year of follow-up, cardiovascular events were 2.4-fold more frequent in that patient subset (Hypertension 2010;56:56-61).

There are no safe and effective medications for the treatment of orthostatic hypotension. Fortunately, this condition generally responds to nondrug measures, including avoidance of fluid-volume depletion, taking up to 2 full minutes to rise from supine to standing in the morning, raising the head of the bed 15 degrees to help maintain a degree of sympathetic nervous system activation during the night, eating a small breakfast, and crossing the legs when feeling unsteady while standing.

Dr. Kaplan disclosed that he is on the speakers bureaus for Pfizer, AstraZeneca, Merck, Novartis, and Bayer.

NEW ORLEANS – Calcium channel blockers and diuretics are the best drugs for treating hypertension in the elderly because they are the most effective at reducing the risk of what elderly patients fear most: stroke, Dr. Norman M. Kaplan asserted at the annual meeting of the American College of Cardiology.

"Coronary disease remains by far the most common cause of mortality [in the United States], but stroke poses the greatest threat to the elderly, not coronary disease," said Dr. Kaplan, professor of internal medicine at the University of Texas, Dallas.

He presented a state-of-the-art perspective on antihypertensive therapy in the elderly from the unique vantage point of having served as a member of the third, fourth, fifth, and sixth Joint National Committees on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Dr. Kaplan noted that a British meta-analysis of 46 randomized trials comparing each of the five major classes of antihypertensive drugs with any other class showed that all of the classes were similarly effective in preventing both coronary disease events and strokes, with one exception: calcium channel blockers had a significantly greater preventive effect on stroke than other agents. Diuretics showed a trend in the same direction that didn’t reach statistical significance (BMJ 2009;338:b1665 [doi:10.1136/BMJ.b1665]).

More recently, a secondary analysis of the 19,257-subject ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) demonstrated that calcium channel blocker–based antihypertensive therapy was particularly effective against stroke in the population most in need of such protection: the elderly. Although there was no significant difference in strokes between amlodipine- and atenolol-based therapy in patients younger than age 65 years, there was a highly significant 30% relative risk reduction with amlodipine in the over-65 group (J. Hypertens. 2011;29:583-91).

The latest thinking regarding mechanism of benefit is that calcium channel blockers and diuretics are more effective at reducing stroke risk because they decrease within-individual variation in systolic blood pressure, unlike angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, all of which significantly increase it. In a meta-analysis of 389 randomized, controlled trials of antihypertensive therapy, stroke risk proved strongly related to this interindividual variation in blood pressure (Lancet 2010;375:906-15).

In addition to reducing stroke risk, calcium channel blockers may also have a neuroprotective effect. A French study of 378 elderly, nondemented, hypertensive patients with the complaint of memory loss showed that memory scores were significantly better in those on a calcium channel blocker than on any other class of antihypertensive medication (J. Hypertens. 2010;28:2485-93). Although that’s an intriguing finding, this was an observational study and needs confirmation, in Dr. Kaplan’s view.

Elderly hypertensives predominantly have isolated systolic hypertension. Because of the extensive body of evidence showing that such patients have a good response rate to diuretic monotherapy, he recommends using a diuretic as the first-line drug.

"I would start chlorthalidone – now having a resurgence as the diuretic of choice – at 12.5 mg/day, and add a calcium channel blocker if additional therapy is needed to reach 150/70 mm Hg, which I think is a rational goal to aim for in the elderly," he said.

Indeed, although the 7th Joint National Committee calls 140 mm Hg the upper limit of normal systolic blood pressure at all ages, nearly all the randomized trials that have shown a protective value for antihypertensive therapy in the elderly enrolled patients with a baseline systolic pressure in excess of 160 mm Hg, and achieved an on-treatment systolic pressure in the 150s or 160s.

"I do not think the evidence we have to date shows protective value for treatment in patients with a baseline systolic blood pressure below 160 mm Hg. There is evidence to suggest that if we lower the elderly patient’s systolic blood pressure more than 10-15 mm Hg, we may be invoking additional trouble rather than protecting the patient," said Dr. Kaplan.

"These are old people who obviously have atherosclerotic vascular disease, even if they don’t show it. Reduction in diastolic blood pressure to 65 mm Hg or lower may reduce their coronary perfusion – which occurs only during diastole – to a degree that could invoke a cardiovascular catastrophe," he continued.

Other important aspects of treating elderly hypertensive patients include identifying and overcoming postural hypotension, encouraging the consumption of one or two alcoholic drinks per day for the well-documented health benefits, starting a statin, and measuring home blood pressures to ensure that an individual really is being treated adequately, Dr. Kaplan said.

The risks posed by orthostatic hypotension were recently highlighted in a study of 374 unselected ambulatory adults with an average age of 70 years and no known cardiovascular disease or other comorbidities. An orthostatic decrease in systolic blood pressure greater than 20 mm Hg was present 2 minutes after standing in 12% of them. Over roughly 1 year of follow-up, cardiovascular events were 2.4-fold more frequent in that patient subset (Hypertension 2010;56:56-61).

There are no safe and effective medications for the treatment of orthostatic hypotension. Fortunately, this condition generally responds to nondrug measures, including avoidance of fluid-volume depletion, taking up to 2 full minutes to rise from supine to standing in the morning, raising the head of the bed 15 degrees to help maintain a degree of sympathetic nervous system activation during the night, eating a small breakfast, and crossing the legs when feeling unsteady while standing.

Dr. Kaplan disclosed that he is on the speakers bureaus for Pfizer, AstraZeneca, Merck, Novartis, and Bayer.