AHA Scientific Sessions 2011

ORLANDO – A large trial of a novel cellular expansion therapy will soon get underway in patients with critical limb ischemia patients and no revascularization options.

Based upon favorable results in initial safety and efficacy studies, the REVIVE-CLI trial of ixmyelocel-T will involve 80 U.S. centers and 594 no-option critical limb ischemia patients with tissue loss at baseline. The primary efficacy end point will be amputation-free survival at 12 months, Dr. William Marston said at the annual scientific sessions of the American Heart Association.

Ixmyelocel-T relies on a 50 mL aspirate of a patient’s bone marrow cells obtained from the ischial tuberosity during a 15-minute office procedure. Over the next 12 days, an automated process is used to expand the cell types believed to be beneficial in critical limb ischemia. The cells are then reintroduced into the patient via 20 intramuscular injections, 0.5 mL each, into the foot, calf, and lower thigh. The procedure takes 20 minutes and is performed in an office setting, explained Dr. Marston, professor of surgery and chief of the division of vascular surgery at the University of North Carolina, Chapel Hill.

The benefits of the process were noted in a double-blind, placebo-controlled, multicenter study involving 72 subjects with infrainguinal occlusive arterial disease deemed not amenable to revascularization. Half of the patients had diabetes. Participants were randomized 2:1 to ixmyelocel-T or to placebo injections. The primary end point was death, major amputation on the treated limb, doubling of wound size from baseline, or new gangrene. During 12 months of follow-up, the primary end point occurred in 67% of controls and in 40% of the ixmyelocel-T group, for a 62% relative reduction in risk.

The major driver of the significant difference in the end point was the change in the wound size. Baseline wounds were present in 45 subjects. Total wound surface area doubled in 5 of 29 ixmyelocel-T–treated patients with baseline wounds, as compared to 7 of 16 controls.

The secondary efficacy end point was amputation-free survival. One-third of controls and one-quarter of ixmyelocel-T–treated patients had an amputation during the study period. The study wasn’t powered to draw conclusions regarding amputation-free survival, according to the surgeon.

The treatment and control groups did not differ in terms of adverse events or study withdrawals due to adverse events.

The laboratory process reduces RBCs, T and B lymphocytes, and CD45+ granulocytes while achieving a 200-fold expansion of monocytes into activated macrophages and a 50-fold increase in mesenchymal stem cells. The mechanism of benefit of ixmyelocel-T, based upon preclinical data, is believed to involve remodeling of ischemic tissue, modulation of inflammation, and promotion of angiogenesis.

"There’s quite a bit of upregulation of tumor necrosis factor-alpha, interleukins, and other proinflammatory cytokines in these patients. We think that this combination of cells that are reintroduced may have benefits other than angiogenesis that may be very important in wound patients," Dr. Marston said.

Other approaches to cellular therapy in critical limb ischemia are being pursued by other groups. Some involve harvesting large quantities of bone marrow under general anesthesia, which Dr. Marston sees as less practical than the ixmyelocel-T strategy.

Dr. Marston declared that he serves as a scientific advisor to Aastrom Biosciences, which is developing ixmyelocel-T.

ORLANDO – A large trial of a novel cellular expansion therapy will soon get underway in patients with critical limb ischemia patients and no revascularization options.

Based upon favorable results in initial safety and efficacy studies, the REVIVE-CLI trial of ixmyelocel-T will involve 80 U.S. centers and 594 no-option critical limb ischemia patients with tissue loss at baseline. The primary efficacy end point will be amputation-free survival at 12 months, Dr. William Marston said at the annual scientific sessions of the American Heart Association.

Ixmyelocel-T relies on a 50 mL aspirate of a patient’s bone marrow cells obtained from the ischial tuberosity during a 15-minute office procedure. Over the next 12 days, an automated process is used to expand the cell types believed to be beneficial in critical limb ischemia. The cells are then reintroduced into the patient via 20 intramuscular injections, 0.5 mL each, into the foot, calf, and lower thigh. The procedure takes 20 minutes and is performed in an office setting, explained Dr. Marston, professor of surgery and chief of the division of vascular surgery at the University of North Carolina, Chapel Hill.

The benefits of the process were noted in a double-blind, placebo-controlled, multicenter study involving 72 subjects with infrainguinal occlusive arterial disease deemed not amenable to revascularization. Half of the patients had diabetes. Participants were randomized 2:1 to ixmyelocel-T or to placebo injections. The primary end point was death, major amputation on the treated limb, doubling of wound size from baseline, or new gangrene. During 12 months of follow-up, the primary end point occurred in 67% of controls and in 40% of the ixmyelocel-T group, for a 62% relative reduction in risk.

The major driver of the significant difference in the end point was the change in the wound size. Baseline wounds were present in 45 subjects. Total wound surface area doubled in 5 of 29 ixmyelocel-T–treated patients with baseline wounds, as compared to 7 of 16 controls.

The secondary efficacy end point was amputation-free survival. One-third of controls and one-quarter of ixmyelocel-T–treated patients had an amputation during the study period. The study wasn’t powered to draw conclusions regarding amputation-free survival, according to the surgeon.

The treatment and control groups did not differ in terms of adverse events or study withdrawals due to adverse events.

The laboratory process reduces RBCs, T and B lymphocytes, and CD45+ granulocytes while achieving a 200-fold expansion of monocytes into activated macrophages and a 50-fold increase in mesenchymal stem cells. The mechanism of benefit of ixmyelocel-T, based upon preclinical data, is believed to involve remodeling of ischemic tissue, modulation of inflammation, and promotion of angiogenesis.

"There’s quite a bit of upregulation of tumor necrosis factor-alpha, interleukins, and other proinflammatory cytokines in these patients. We think that this combination of cells that are reintroduced may have benefits other than angiogenesis that may be very important in wound patients," Dr. Marston said.

Other approaches to cellular therapy in critical limb ischemia are being pursued by other groups. Some involve harvesting large quantities of bone marrow under general anesthesia, which Dr. Marston sees as less practical than the ixmyelocel-T strategy.

Dr. Marston declared that he serves as a scientific advisor to Aastrom Biosciences, which is developing ixmyelocel-T.

ORLANDO – A large trial of a novel cellular expansion therapy will soon get underway in patients with critical limb ischemia patients and no revascularization options.

Based upon favorable results in initial safety and efficacy studies, the REVIVE-CLI trial of ixmyelocel-T will involve 80 U.S. centers and 594 no-option critical limb ischemia patients with tissue loss at baseline. The primary efficacy end point will be amputation-free survival at 12 months, Dr. William Marston said at the annual scientific sessions of the American Heart Association.

Ixmyelocel-T relies on a 50 mL aspirate of a patient’s bone marrow cells obtained from the ischial tuberosity during a 15-minute office procedure. Over the next 12 days, an automated process is used to expand the cell types believed to be beneficial in critical limb ischemia. The cells are then reintroduced into the patient via 20 intramuscular injections, 0.5 mL each, into the foot, calf, and lower thigh. The procedure takes 20 minutes and is performed in an office setting, explained Dr. Marston, professor of surgery and chief of the division of vascular surgery at the University of North Carolina, Chapel Hill.

The benefits of the process were noted in a double-blind, placebo-controlled, multicenter study involving 72 subjects with infrainguinal occlusive arterial disease deemed not amenable to revascularization. Half of the patients had diabetes. Participants were randomized 2:1 to ixmyelocel-T or to placebo injections. The primary end point was death, major amputation on the treated limb, doubling of wound size from baseline, or new gangrene. During 12 months of follow-up, the primary end point occurred in 67% of controls and in 40% of the ixmyelocel-T group, for a 62% relative reduction in risk.

The major driver of the significant difference in the end point was the change in the wound size. Baseline wounds were present in 45 subjects. Total wound surface area doubled in 5 of 29 ixmyelocel-T–treated patients with baseline wounds, as compared to 7 of 16 controls.

The secondary efficacy end point was amputation-free survival. One-third of controls and one-quarter of ixmyelocel-T–treated patients had an amputation during the study period. The study wasn’t powered to draw conclusions regarding amputation-free survival, according to the surgeon.

The treatment and control groups did not differ in terms of adverse events or study withdrawals due to adverse events.

The laboratory process reduces RBCs, T and B lymphocytes, and CD45+ granulocytes while achieving a 200-fold expansion of monocytes into activated macrophages and a 50-fold increase in mesenchymal stem cells. The mechanism of benefit of ixmyelocel-T, based upon preclinical data, is believed to involve remodeling of ischemic tissue, modulation of inflammation, and promotion of angiogenesis.

"There’s quite a bit of upregulation of tumor necrosis factor-alpha, interleukins, and other proinflammatory cytokines in these patients. We think that this combination of cells that are reintroduced may have benefits other than angiogenesis that may be very important in wound patients," Dr. Marston said.

Other approaches to cellular therapy in critical limb ischemia are being pursued by other groups. Some involve harvesting large quantities of bone marrow under general anesthesia, which Dr. Marston sees as less practical than the ixmyelocel-T strategy.

Dr. Marston declared that he serves as a scientific advisor to Aastrom Biosciences, which is developing ixmyelocel-T.

ORLANDO – Beta-blockers appear to be cardioprotective in breast cancer patients on trastuzumab, according to a prospective case-control study.

The risk of developing new-onset heart failure or left ventricular dysfunction during 1 year on trastuzumab (Herceptin) was 65% lower in 30 breast cancer patients who were incidentally on a beta-blocker at the start of the monoclonal antibody therapy than in 167 other breast cancer patients who were not, Thomas B. Cook, Ph.D., reported at the annual scientific sessions of the American Heart Association.

The women on a beta-blocker averaged 59 years of age, a full 8 years older than the breast cancer patients not on a beta-blocker. The patients on a beta-blocker also had significantly higher rates of hypertension, diabetes, obesity, and smoking. After adjustment for these traditional cardiovascular risk factors as well as other factors predisposing to heart failure, including prior treatment with anthracyclines or radiation therapy, the beta-blocker group had an adjusted 83% lower risk of developing cardiotoxicity during 1 year of follow-up on trastuzumab (P = .006).

This is a small hypothesis-generating study. The findings warrant a proper randomized controlled trial assessing the impact of prophylactic beta-blocker therapy in breast cancer patients going on trastuzumab, Dr. Cook asserted.

In all, 22 of the 197 breast cancer patients were on an ACE inhibitor at the time they started on trastuzumab. Logistic regression analysis indicated no cardioprotective effect for this class of medication, according to Dr. Cook of the Cleveland Clinic Foundation.

New-onset heart failure was diagnosed in 11% of patients not on a beta-blocker and in none who were. Left ventricular dysfunction – defined as an echocardiographically documented ejection fraction decline of at least 10% – occurred in 40% of trastuzumab users not on a beta-blocker, compared to 20% who were.

A trajectory analysis of serial echocardiographic exams revealed overall significant declines in left ventricular ejection fraction in patients during their year of follow-up on trastuzumab; however, the decline was markedly steeper in those who were not on a beta-blocker.

Interestingly, neither prior treatment with anthracyclines, even in excess of four cycles, nor other prior chemotherapy were predictive of cardiotoxicity in this series of trastuzumab-treated women. Current smoking, however, was associated with a 4.2-fold increased risk.

Dr. Cook reported no financial conflicts.

ORLANDO – Beta-blockers appear to be cardioprotective in breast cancer patients on trastuzumab, according to a prospective case-control study.

The risk of developing new-onset heart failure or left ventricular dysfunction during 1 year on trastuzumab (Herceptin) was 65% lower in 30 breast cancer patients who were incidentally on a beta-blocker at the start of the monoclonal antibody therapy than in 167 other breast cancer patients who were not, Thomas B. Cook, Ph.D., reported at the annual scientific sessions of the American Heart Association.

The women on a beta-blocker averaged 59 years of age, a full 8 years older than the breast cancer patients not on a beta-blocker. The patients on a beta-blocker also had significantly higher rates of hypertension, diabetes, obesity, and smoking. After adjustment for these traditional cardiovascular risk factors as well as other factors predisposing to heart failure, including prior treatment with anthracyclines or radiation therapy, the beta-blocker group had an adjusted 83% lower risk of developing cardiotoxicity during 1 year of follow-up on trastuzumab (P = .006).

This is a small hypothesis-generating study. The findings warrant a proper randomized controlled trial assessing the impact of prophylactic beta-blocker therapy in breast cancer patients going on trastuzumab, Dr. Cook asserted.

In all, 22 of the 197 breast cancer patients were on an ACE inhibitor at the time they started on trastuzumab. Logistic regression analysis indicated no cardioprotective effect for this class of medication, according to Dr. Cook of the Cleveland Clinic Foundation.

New-onset heart failure was diagnosed in 11% of patients not on a beta-blocker and in none who were. Left ventricular dysfunction – defined as an echocardiographically documented ejection fraction decline of at least 10% – occurred in 40% of trastuzumab users not on a beta-blocker, compared to 20% who were.

A trajectory analysis of serial echocardiographic exams revealed overall significant declines in left ventricular ejection fraction in patients during their year of follow-up on trastuzumab; however, the decline was markedly steeper in those who were not on a beta-blocker.

Interestingly, neither prior treatment with anthracyclines, even in excess of four cycles, nor other prior chemotherapy were predictive of cardiotoxicity in this series of trastuzumab-treated women. Current smoking, however, was associated with a 4.2-fold increased risk.

Dr. Cook reported no financial conflicts.

ORLANDO – Beta-blockers appear to be cardioprotective in breast cancer patients on trastuzumab, according to a prospective case-control study.

The risk of developing new-onset heart failure or left ventricular dysfunction during 1 year on trastuzumab (Herceptin) was 65% lower in 30 breast cancer patients who were incidentally on a beta-blocker at the start of the monoclonal antibody therapy than in 167 other breast cancer patients who were not, Thomas B. Cook, Ph.D., reported at the annual scientific sessions of the American Heart Association.

The women on a beta-blocker averaged 59 years of age, a full 8 years older than the breast cancer patients not on a beta-blocker. The patients on a beta-blocker also had significantly higher rates of hypertension, diabetes, obesity, and smoking. After adjustment for these traditional cardiovascular risk factors as well as other factors predisposing to heart failure, including prior treatment with anthracyclines or radiation therapy, the beta-blocker group had an adjusted 83% lower risk of developing cardiotoxicity during 1 year of follow-up on trastuzumab (P = .006).

This is a small hypothesis-generating study. The findings warrant a proper randomized controlled trial assessing the impact of prophylactic beta-blocker therapy in breast cancer patients going on trastuzumab, Dr. Cook asserted.

In all, 22 of the 197 breast cancer patients were on an ACE inhibitor at the time they started on trastuzumab. Logistic regression analysis indicated no cardioprotective effect for this class of medication, according to Dr. Cook of the Cleveland Clinic Foundation.

New-onset heart failure was diagnosed in 11% of patients not on a beta-blocker and in none who were. Left ventricular dysfunction – defined as an echocardiographically documented ejection fraction decline of at least 10% – occurred in 40% of trastuzumab users not on a beta-blocker, compared to 20% who were.

A trajectory analysis of serial echocardiographic exams revealed overall significant declines in left ventricular ejection fraction in patients during their year of follow-up on trastuzumab; however, the decline was markedly steeper in those who were not on a beta-blocker.

Interestingly, neither prior treatment with anthracyclines, even in excess of four cycles, nor other prior chemotherapy were predictive of cardiotoxicity in this series of trastuzumab-treated women. Current smoking, however, was associated with a 4.2-fold increased risk.

Dr. Cook reported no financial conflicts.

ORLANDO – Minimally invasive surgical ablation for atrial fibrillation that is refractory to antiarrhythmic agents was significantly more effective than catheter ablation in the first-ever randomized trial comparing the two therapies.

The higher rate of freedom from left atrial arrhythmia that was achieved surgically came at a cost of more procedural complications, most of which were managed conservatively and without prolongation of hospitalization.

The clinical trial was conducted at two European medical centers. It involved 124 patients with drug-refractory paroxysmal or persistent atrial fibrillation (AF) who were deemed to be at high risk of having an unsuccessful catheter ablation procedure.

Two-thirds of participants were judged high risk because they had experienced a return of their AF after a prior catheter ablation, whereas the remaining patients were considered at high risk for an unsuccessful catheter ablation because of left atrial enlargement and hypertension, Dr. Lucas V.A. Boersma explained when presenting the results of the FAST (Ablation or Surgery for Atrial Fibrillation Treatment) trial at the annual scientific sessions of the American Heart Association.

Patients were randomized to pulmonary vein isolation by catheter ablation or to a video-assisted thoracoscopic surgical ablation procedure pioneered at the University of Cincinnati (J. Thorac. Cardiovasc. Surg. 2005;130:797-802). Surgical ablation was performed under general anesthesia, but unlike catheter ablation it did not include fluoroscopy, noted Dr. Boersma, a cardiologist at St. Antonius Hospital, Nieuwegein, the Netherlands.

The primary efficacy end point was freedom from left atrial arrhythmia lasting longer than 30 seconds without antiarrhythmic drugs at 12 months post procedure; this was achieved in 66% of the surgical ablation group, compared with 37% of the catheter ablation group.

Adverse events occurred during the 12 months of follow-up in 34% of the surgical group, compared with 16% of the catheter ablation group. Most of the adverse events in the surgical group were procedural complications, consisting mainly of pneumothorax and bleeding.

Discussant Dr. A. Marc Gillinov, a cardiac surgeon at the Cleveland Clinic, praised FAST as a well-designed, clearly focused study with important clinical implications, given that roughly one-fourth of Americans will eventually develop AF.

"The clear inference from this trial is that if catheter ablation fails and a patient comes to me, I will say to that patient, ‘We have many options, but we now have data to suggest we should discuss surgical ablation as one of those options because if you’ve had a catheter ablation and it failed, surgical ablation has a good chance of restoring you to sinus rhythm," he said.

"Most of the excess morbidity was related to chest drainage: retained fluid or air. I think it’s reasonable to state that those complications are not major and are probably preventable," the surgeon added.

The FAST trial was funded by St. Antonius Hospital and the University of Barcelona Thorax Institute. Dr. Boersma disclosed that he has served as a consultant to Medtronic, and Dr. Gillinov is a consultant to Edwards Lifesciences and AtriCure.

Concurrently with Dr. Boersma’s presentation at the AHA meeting, the FAST results were published in Circulation (doi:10.1161/CIRCULATIONAHA.111.074047).

ORLANDO – Minimally invasive surgical ablation for atrial fibrillation that is refractory to antiarrhythmic agents was significantly more effective than catheter ablation in the first-ever randomized trial comparing the two therapies.

The higher rate of freedom from left atrial arrhythmia that was achieved surgically came at a cost of more procedural complications, most of which were managed conservatively and without prolongation of hospitalization.

The clinical trial was conducted at two European medical centers. It involved 124 patients with drug-refractory paroxysmal or persistent atrial fibrillation (AF) who were deemed to be at high risk of having an unsuccessful catheter ablation procedure.

Two-thirds of participants were judged high risk because they had experienced a return of their AF after a prior catheter ablation, whereas the remaining patients were considered at high risk for an unsuccessful catheter ablation because of left atrial enlargement and hypertension, Dr. Lucas V.A. Boersma explained when presenting the results of the FAST (Ablation or Surgery for Atrial Fibrillation Treatment) trial at the annual scientific sessions of the American Heart Association.

Patients were randomized to pulmonary vein isolation by catheter ablation or to a video-assisted thoracoscopic surgical ablation procedure pioneered at the University of Cincinnati (J. Thorac. Cardiovasc. Surg. 2005;130:797-802). Surgical ablation was performed under general anesthesia, but unlike catheter ablation it did not include fluoroscopy, noted Dr. Boersma, a cardiologist at St. Antonius Hospital, Nieuwegein, the Netherlands.

The primary efficacy end point was freedom from left atrial arrhythmia lasting longer than 30 seconds without antiarrhythmic drugs at 12 months post procedure; this was achieved in 66% of the surgical ablation group, compared with 37% of the catheter ablation group.

Adverse events occurred during the 12 months of follow-up in 34% of the surgical group, compared with 16% of the catheter ablation group. Most of the adverse events in the surgical group were procedural complications, consisting mainly of pneumothorax and bleeding.

Discussant Dr. A. Marc Gillinov, a cardiac surgeon at the Cleveland Clinic, praised FAST as a well-designed, clearly focused study with important clinical implications, given that roughly one-fourth of Americans will eventually develop AF.

"The clear inference from this trial is that if catheter ablation fails and a patient comes to me, I will say to that patient, ‘We have many options, but we now have data to suggest we should discuss surgical ablation as one of those options because if you’ve had a catheter ablation and it failed, surgical ablation has a good chance of restoring you to sinus rhythm," he said.

"Most of the excess morbidity was related to chest drainage: retained fluid or air. I think it’s reasonable to state that those complications are not major and are probably preventable," the surgeon added.

The FAST trial was funded by St. Antonius Hospital and the University of Barcelona Thorax Institute. Dr. Boersma disclosed that he has served as a consultant to Medtronic, and Dr. Gillinov is a consultant to Edwards Lifesciences and AtriCure.

Concurrently with Dr. Boersma’s presentation at the AHA meeting, the FAST results were published in Circulation (doi:10.1161/CIRCULATIONAHA.111.074047).

ORLANDO – Minimally invasive surgical ablation for atrial fibrillation that is refractory to antiarrhythmic agents was significantly more effective than catheter ablation in the first-ever randomized trial comparing the two therapies.

The higher rate of freedom from left atrial arrhythmia that was achieved surgically came at a cost of more procedural complications, most of which were managed conservatively and without prolongation of hospitalization.

The clinical trial was conducted at two European medical centers. It involved 124 patients with drug-refractory paroxysmal or persistent atrial fibrillation (AF) who were deemed to be at high risk of having an unsuccessful catheter ablation procedure.

Two-thirds of participants were judged high risk because they had experienced a return of their AF after a prior catheter ablation, whereas the remaining patients were considered at high risk for an unsuccessful catheter ablation because of left atrial enlargement and hypertension, Dr. Lucas V.A. Boersma explained when presenting the results of the FAST (Ablation or Surgery for Atrial Fibrillation Treatment) trial at the annual scientific sessions of the American Heart Association.

Patients were randomized to pulmonary vein isolation by catheter ablation or to a video-assisted thoracoscopic surgical ablation procedure pioneered at the University of Cincinnati (J. Thorac. Cardiovasc. Surg. 2005;130:797-802). Surgical ablation was performed under general anesthesia, but unlike catheter ablation it did not include fluoroscopy, noted Dr. Boersma, a cardiologist at St. Antonius Hospital, Nieuwegein, the Netherlands.

The primary efficacy end point was freedom from left atrial arrhythmia lasting longer than 30 seconds without antiarrhythmic drugs at 12 months post procedure; this was achieved in 66% of the surgical ablation group, compared with 37% of the catheter ablation group.

Adverse events occurred during the 12 months of follow-up in 34% of the surgical group, compared with 16% of the catheter ablation group. Most of the adverse events in the surgical group were procedural complications, consisting mainly of pneumothorax and bleeding.

Discussant Dr. A. Marc Gillinov, a cardiac surgeon at the Cleveland Clinic, praised FAST as a well-designed, clearly focused study with important clinical implications, given that roughly one-fourth of Americans will eventually develop AF.

"The clear inference from this trial is that if catheter ablation fails and a patient comes to me, I will say to that patient, ‘We have many options, but we now have data to suggest we should discuss surgical ablation as one of those options because if you’ve had a catheter ablation and it failed, surgical ablation has a good chance of restoring you to sinus rhythm," he said.

"Most of the excess morbidity was related to chest drainage: retained fluid or air. I think it’s reasonable to state that those complications are not major and are probably preventable," the surgeon added.

The FAST trial was funded by St. Antonius Hospital and the University of Barcelona Thorax Institute. Dr. Boersma disclosed that he has served as a consultant to Medtronic, and Dr. Gillinov is a consultant to Edwards Lifesciences and AtriCure.

Concurrently with Dr. Boersma’s presentation at the AHA meeting, the FAST results were published in Circulation (doi:10.1161/CIRCULATIONAHA.111.074047).

ORLANDO –The higher a patient’s baseline high-sensitivity C-reactive protein level in the landmark JUPITER study, the greater the incidence of new-onset atrial fibrillation during follow-up, and randomization to rosuvastatin significantly reduced this risk.

Among the 17,120 apparently healthy participants in JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) with no baseline history of atrial fibrillation or other arrhythmia, those in the highest baseline tertile for C-reactive protein (CRP) – that is, more than 5.8 mg/L – had an adjusted 1.96-fold greater incidence of new-onset atrial fibrillation during follow-up, compared with those in the lowest tertile for the inflammatory biomarker, with a CRP of less than 3.2 mg/L, Dr. Jessica M. Peña reported at the annual scientific sessions of the American Heart Association.

Those in the middle tertile had a 1.7-fold increased risk of developing atrial fibrillation after adjustment for age, gender, race, exercise, alcohol intake, current smoking, metabolic syndrome, hypertension, body mass index, and glycosylated hemoglobin.

The incidence of atrial fibrillation was 0.83 cases per 100 person-years in subjects in the top tertile for baseline CRP, 0.75 per 100 person-years for those in the middle tertile, and 0.43 per 100 person-years among patients in the lowest tertile, according to Dr. Peña of Brigham and Women’s Hospital, Boston.

Rosuvastatin (Crestor) proved to have a significant impact upon this risk. The crude incidence was 1.6% with placebo, compared to 1.2% with the statin, which worked out to an adjusted 27% reduction in relative risk in the rosuvastatin group.

The presumed mechanism of benefit lies in the mounting evidence suggesting that inflammation plays a role in both the initiation and maintenance of atrial fibrillation. Statins have anti-inflammatory properties that could be helpful in preventing the arrhythmia, she observed.

It’s important to note that this was a post hoc analysis. Atrial fibrillation was not a prespecified study end point, Dr. Peña stressed. She and her coinvestigators undertook this exploratory analysis because other studies have yielded mixed results regarding statins and atrial fibrillation. The JUPITER analysis provided an opportunity to focus on a population with an underlying proinflammatory state as manifest by the requirement that participants had to have a baseline CRP of at least 2 mg/L.

She and her JUPITER colleagues are now analyzing the data on the relationship between change over time in CRP level and incident atrial fibrillation.

A recently published meta-analysis by University of Oxford (England) researchers looked at published and unpublished data from randomized clinical trials addressing the relationship between statin therapy and atrial fibrillation. The investigators concluded that the available evidence doesn’t support the notion that statins reduce the risk of atrial fibrillation (BMJ 2011 March 16 [doi: 10.1136/bmj.d1250]).

How can this be reconciled with the new JUPITER findings? Dr. Peña surmised that the different study conclusions were probably due to the fact that the various trials involved very different populations and methods of detecting atrial fibrillation.

"Unfortunately, none of these trials, including JUPITER, had atrial fibrillation as a prespecified end point. In the future that will change, but I think until we have better data we can’t definitively answer the question of whether statins protect against atrial fibrillation," Dr. Peña said.

The primary composite end point in JUPITER was myocardial infarction, stroke, cardiovascular death, arterial revascularization, or hospitalization for unstable angina. The rosuvastatin group had a 44% risk reduction compared to controls (N. Engl. J. Med. 2008;359: 2195-207).

JUPITER was funded by AstraZeneca. Dr. Peña reported having no relevant conflicts of interest.

ORLANDO –The higher a patient’s baseline high-sensitivity C-reactive protein level in the landmark JUPITER study, the greater the incidence of new-onset atrial fibrillation during follow-up, and randomization to rosuvastatin significantly reduced this risk.

Among the 17,120 apparently healthy participants in JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) with no baseline history of atrial fibrillation or other arrhythmia, those in the highest baseline tertile for C-reactive protein (CRP) – that is, more than 5.8 mg/L – had an adjusted 1.96-fold greater incidence of new-onset atrial fibrillation during follow-up, compared with those in the lowest tertile for the inflammatory biomarker, with a CRP of less than 3.2 mg/L, Dr. Jessica M. Peña reported at the annual scientific sessions of the American Heart Association.

Those in the middle tertile had a 1.7-fold increased risk of developing atrial fibrillation after adjustment for age, gender, race, exercise, alcohol intake, current smoking, metabolic syndrome, hypertension, body mass index, and glycosylated hemoglobin.

The incidence of atrial fibrillation was 0.83 cases per 100 person-years in subjects in the top tertile for baseline CRP, 0.75 per 100 person-years for those in the middle tertile, and 0.43 per 100 person-years among patients in the lowest tertile, according to Dr. Peña of Brigham and Women’s Hospital, Boston.

Rosuvastatin (Crestor) proved to have a significant impact upon this risk. The crude incidence was 1.6% with placebo, compared to 1.2% with the statin, which worked out to an adjusted 27% reduction in relative risk in the rosuvastatin group.

The presumed mechanism of benefit lies in the mounting evidence suggesting that inflammation plays a role in both the initiation and maintenance of atrial fibrillation. Statins have anti-inflammatory properties that could be helpful in preventing the arrhythmia, she observed.

It’s important to note that this was a post hoc analysis. Atrial fibrillation was not a prespecified study end point, Dr. Peña stressed. She and her coinvestigators undertook this exploratory analysis because other studies have yielded mixed results regarding statins and atrial fibrillation. The JUPITER analysis provided an opportunity to focus on a population with an underlying proinflammatory state as manifest by the requirement that participants had to have a baseline CRP of at least 2 mg/L.

She and her JUPITER colleagues are now analyzing the data on the relationship between change over time in CRP level and incident atrial fibrillation.

A recently published meta-analysis by University of Oxford (England) researchers looked at published and unpublished data from randomized clinical trials addressing the relationship between statin therapy and atrial fibrillation. The investigators concluded that the available evidence doesn’t support the notion that statins reduce the risk of atrial fibrillation (BMJ 2011 March 16 [doi: 10.1136/bmj.d1250]).

How can this be reconciled with the new JUPITER findings? Dr. Peña surmised that the different study conclusions were probably due to the fact that the various trials involved very different populations and methods of detecting atrial fibrillation.

"Unfortunately, none of these trials, including JUPITER, had atrial fibrillation as a prespecified end point. In the future that will change, but I think until we have better data we can’t definitively answer the question of whether statins protect against atrial fibrillation," Dr. Peña said.

The primary composite end point in JUPITER was myocardial infarction, stroke, cardiovascular death, arterial revascularization, or hospitalization for unstable angina. The rosuvastatin group had a 44% risk reduction compared to controls (N. Engl. J. Med. 2008;359: 2195-207).

JUPITER was funded by AstraZeneca. Dr. Peña reported having no relevant conflicts of interest.

ORLANDO –The higher a patient’s baseline high-sensitivity C-reactive protein level in the landmark JUPITER study, the greater the incidence of new-onset atrial fibrillation during follow-up, and randomization to rosuvastatin significantly reduced this risk.

Among the 17,120 apparently healthy participants in JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) with no baseline history of atrial fibrillation or other arrhythmia, those in the highest baseline tertile for C-reactive protein (CRP) – that is, more than 5.8 mg/L – had an adjusted 1.96-fold greater incidence of new-onset atrial fibrillation during follow-up, compared with those in the lowest tertile for the inflammatory biomarker, with a CRP of less than 3.2 mg/L, Dr. Jessica M. Peña reported at the annual scientific sessions of the American Heart Association.

Those in the middle tertile had a 1.7-fold increased risk of developing atrial fibrillation after adjustment for age, gender, race, exercise, alcohol intake, current smoking, metabolic syndrome, hypertension, body mass index, and glycosylated hemoglobin.

The incidence of atrial fibrillation was 0.83 cases per 100 person-years in subjects in the top tertile for baseline CRP, 0.75 per 100 person-years for those in the middle tertile, and 0.43 per 100 person-years among patients in the lowest tertile, according to Dr. Peña of Brigham and Women’s Hospital, Boston.

Rosuvastatin (Crestor) proved to have a significant impact upon this risk. The crude incidence was 1.6% with placebo, compared to 1.2% with the statin, which worked out to an adjusted 27% reduction in relative risk in the rosuvastatin group.

The presumed mechanism of benefit lies in the mounting evidence suggesting that inflammation plays a role in both the initiation and maintenance of atrial fibrillation. Statins have anti-inflammatory properties that could be helpful in preventing the arrhythmia, she observed.

It’s important to note that this was a post hoc analysis. Atrial fibrillation was not a prespecified study end point, Dr. Peña stressed. She and her coinvestigators undertook this exploratory analysis because other studies have yielded mixed results regarding statins and atrial fibrillation. The JUPITER analysis provided an opportunity to focus on a population with an underlying proinflammatory state as manifest by the requirement that participants had to have a baseline CRP of at least 2 mg/L.

She and her JUPITER colleagues are now analyzing the data on the relationship between change over time in CRP level and incident atrial fibrillation.

A recently published meta-analysis by University of Oxford (England) researchers looked at published and unpublished data from randomized clinical trials addressing the relationship between statin therapy and atrial fibrillation. The investigators concluded that the available evidence doesn’t support the notion that statins reduce the risk of atrial fibrillation (BMJ 2011 March 16 [doi: 10.1136/bmj.d1250]).

How can this be reconciled with the new JUPITER findings? Dr. Peña surmised that the different study conclusions were probably due to the fact that the various trials involved very different populations and methods of detecting atrial fibrillation.

"Unfortunately, none of these trials, including JUPITER, had atrial fibrillation as a prespecified end point. In the future that will change, but I think until we have better data we can’t definitively answer the question of whether statins protect against atrial fibrillation," Dr. Peña said.

The primary composite end point in JUPITER was myocardial infarction, stroke, cardiovascular death, arterial revascularization, or hospitalization for unstable angina. The rosuvastatin group had a 44% risk reduction compared to controls (N. Engl. J. Med. 2008;359: 2195-207).

JUPITER was funded by AstraZeneca. Dr. Peña reported having no relevant conflicts of interest.

ORLANDO – Patients with atrial fibrillation have an underappreciated high rate of gastrointestinal events, including dyspepsia, GI bleeds, diverticulitis, and gastroesophageal reflux disease.

The rate of symptomatic GI events in patients with atrial fibrillation (AF) rises with increasing CHADS2 score and age. In those AF patients at increased risk for GI events – elderly patients with a higher CHADS2 score – it makes sense for physicians to steer clear whenever possible of the many medications known to increase GI symptoms, Dr. François Laliberté advised at the annual scientific session of the American Heart Association.

He presented an analysis of insurance claims data from the Thomson Reuters MarketScan database for 2005-2009. The study included 413,618 adults diagnosed for the first time with AF and who had no GI events in the 180 days immediately beforehand.

During a mean follow-up of 563 days, the incidence of any diagnosed GI event among these patients – all free of GI symptoms at baseline – was 38.8 events per 100 patient-years, or roughly 39%.

By far the most common GI event was dyspepsia, with an incidence of 14.7 cases per 100 patient-years. This was followed in frequency by diverticula of the intestine at 5.2, gastroesophageal reflux disease at 4.8, and GI bleeding at 4.3 cases per 100 patient-years, reported Dr. Laliberté of the Analysis Group, Montreal.

The rate of GI-related hospitalization was 9.7 per 100 patient-years.

The incidence of GI events was gender-related: 43.6 per 100 patient-years among women with AF and 35.5 in men. The GI event rate steadily rose with age, from 32.2 events per 100 patient-years in patients under age 65 to 52.7 in those age 85 and up.

Patients with a CHADS2 score of 0 had a GI event rate of 30.3 per 100 patient-years. The rate climbed steeply to 41.6 with a CHADS2 score of 1-2, 56.9 with a CHADS2 of 3-4, and 74.5 in patients with a CHADS2 of 5-6.

At baseline, 62% of the AF patients were on one or more medications known to increase the risk of GI events. Leading the list were anticoagulants, used by 19.4% of the study population. Other commonly used medications that promote GI toxicity included opioids, antiplatelet agents, corticosteroids, NSAIDs, selective serotonin receptor inhibitors, bisphosphonates, and calcium channel blockers.

This study was funded by Janssen Scientific Affairs.

ORLANDO – Patients with atrial fibrillation have an underappreciated high rate of gastrointestinal events, including dyspepsia, GI bleeds, diverticulitis, and gastroesophageal reflux disease.

The rate of symptomatic GI events in patients with atrial fibrillation (AF) rises with increasing CHADS2 score and age. In those AF patients at increased risk for GI events – elderly patients with a higher CHADS2 score – it makes sense for physicians to steer clear whenever possible of the many medications known to increase GI symptoms, Dr. François Laliberté advised at the annual scientific session of the American Heart Association.

He presented an analysis of insurance claims data from the Thomson Reuters MarketScan database for 2005-2009. The study included 413,618 adults diagnosed for the first time with AF and who had no GI events in the 180 days immediately beforehand.

During a mean follow-up of 563 days, the incidence of any diagnosed GI event among these patients – all free of GI symptoms at baseline – was 38.8 events per 100 patient-years, or roughly 39%.

By far the most common GI event was dyspepsia, with an incidence of 14.7 cases per 100 patient-years. This was followed in frequency by diverticula of the intestine at 5.2, gastroesophageal reflux disease at 4.8, and GI bleeding at 4.3 cases per 100 patient-years, reported Dr. Laliberté of the Analysis Group, Montreal.

The rate of GI-related hospitalization was 9.7 per 100 patient-years.

The incidence of GI events was gender-related: 43.6 per 100 patient-years among women with AF and 35.5 in men. The GI event rate steadily rose with age, from 32.2 events per 100 patient-years in patients under age 65 to 52.7 in those age 85 and up.

Patients with a CHADS2 score of 0 had a GI event rate of 30.3 per 100 patient-years. The rate climbed steeply to 41.6 with a CHADS2 score of 1-2, 56.9 with a CHADS2 of 3-4, and 74.5 in patients with a CHADS2 of 5-6.

At baseline, 62% of the AF patients were on one or more medications known to increase the risk of GI events. Leading the list were anticoagulants, used by 19.4% of the study population. Other commonly used medications that promote GI toxicity included opioids, antiplatelet agents, corticosteroids, NSAIDs, selective serotonin receptor inhibitors, bisphosphonates, and calcium channel blockers.

This study was funded by Janssen Scientific Affairs.

ORLANDO – Patients with atrial fibrillation have an underappreciated high rate of gastrointestinal events, including dyspepsia, GI bleeds, diverticulitis, and gastroesophageal reflux disease.

The rate of symptomatic GI events in patients with atrial fibrillation (AF) rises with increasing CHADS2 score and age. In those AF patients at increased risk for GI events – elderly patients with a higher CHADS2 score – it makes sense for physicians to steer clear whenever possible of the many medications known to increase GI symptoms, Dr. François Laliberté advised at the annual scientific session of the American Heart Association.

He presented an analysis of insurance claims data from the Thomson Reuters MarketScan database for 2005-2009. The study included 413,618 adults diagnosed for the first time with AF and who had no GI events in the 180 days immediately beforehand.

During a mean follow-up of 563 days, the incidence of any diagnosed GI event among these patients – all free of GI symptoms at baseline – was 38.8 events per 100 patient-years, or roughly 39%.

By far the most common GI event was dyspepsia, with an incidence of 14.7 cases per 100 patient-years. This was followed in frequency by diverticula of the intestine at 5.2, gastroesophageal reflux disease at 4.8, and GI bleeding at 4.3 cases per 100 patient-years, reported Dr. Laliberté of the Analysis Group, Montreal.

The rate of GI-related hospitalization was 9.7 per 100 patient-years.

The incidence of GI events was gender-related: 43.6 per 100 patient-years among women with AF and 35.5 in men. The GI event rate steadily rose with age, from 32.2 events per 100 patient-years in patients under age 65 to 52.7 in those age 85 and up.

Patients with a CHADS2 score of 0 had a GI event rate of 30.3 per 100 patient-years. The rate climbed steeply to 41.6 with a CHADS2 score of 1-2, 56.9 with a CHADS2 of 3-4, and 74.5 in patients with a CHADS2 of 5-6.

At baseline, 62% of the AF patients were on one or more medications known to increase the risk of GI events. Leading the list were anticoagulants, used by 19.4% of the study population. Other commonly used medications that promote GI toxicity included opioids, antiplatelet agents, corticosteroids, NSAIDs, selective serotonin receptor inhibitors, bisphosphonates, and calcium channel blockers.

This study was funded by Janssen Scientific Affairs.

ORLANDO – The phosphodiesterase type 5 inhibitor vardenafil significantly improved clinical symptoms and digital blood flow in patients with primary or secondary Raynaud syndrome in a randomized, placebo-controlled, double-blind crossover trial.

Thus, vardenafil (Levitra) appears to provide a novel, albeit off-label, therapeutic option in patients with this common, often disabling disorder for which treatment options have been limited, Dr. Evren Caglayan declared at the annual Scientific Sessions of the American Heart Association.

The study involved 53 patients with primary or secondary Raynaud syndrome who in double-blind fashion received vardenafil at 10 mg twice daily or placebo for 6 weeks. A subsequent weeklong washout period was followed crossover to 6 weeks in the other study arm.

Digital blood flow measured by laser Doppler flowmetry at room temperature after 6 weeks of continuous vardenafil therapy improved by a mean of 18.7%, compared to baseline but was unchanged during the control period, according to Dr. Caglayan of the University of Cologne (Germany).

A standardized patient questionnaire administered daily was used to assess clinical symptoms. The results were summarized as the Raynaud Condition Score. During vardenafil therapy the score declined from a baseline mean of 4.3 to 3.0 (P less than .01), mainly reflecting fewer Raynaud attacks and shorter cumulative duration of attacks.

No treatment-related adverse events occurred.

These randomized trial results confirm the favorable findings of an earlier open-label 40-patient study conducted by Dr. Caglayan and coworkers (Arch. Intern. Med. 2006;166:231-3).

The therapeutic rationale for using vardenafil in patients with Raynaud syndrome lies in the broad observation that PDE5 inhibitors exert vasodilatory properties, particularly in diseased tissue.

Dr. Caglayan declared having no financial conflicts with regard to this study, which was funded by Bayer.

ORLANDO – The phosphodiesterase type 5 inhibitor vardenafil significantly improved clinical symptoms and digital blood flow in patients with primary or secondary Raynaud syndrome in a randomized, placebo-controlled, double-blind crossover trial.

Thus, vardenafil (Levitra) appears to provide a novel, albeit off-label, therapeutic option in patients with this common, often disabling disorder for which treatment options have been limited, Dr. Evren Caglayan declared at the annual Scientific Sessions of the American Heart Association.

The study involved 53 patients with primary or secondary Raynaud syndrome who in double-blind fashion received vardenafil at 10 mg twice daily or placebo for 6 weeks. A subsequent weeklong washout period was followed crossover to 6 weeks in the other study arm.

Digital blood flow measured by laser Doppler flowmetry at room temperature after 6 weeks of continuous vardenafil therapy improved by a mean of 18.7%, compared to baseline but was unchanged during the control period, according to Dr. Caglayan of the University of Cologne (Germany).

A standardized patient questionnaire administered daily was used to assess clinical symptoms. The results were summarized as the Raynaud Condition Score. During vardenafil therapy the score declined from a baseline mean of 4.3 to 3.0 (P less than .01), mainly reflecting fewer Raynaud attacks and shorter cumulative duration of attacks.

No treatment-related adverse events occurred.

These randomized trial results confirm the favorable findings of an earlier open-label 40-patient study conducted by Dr. Caglayan and coworkers (Arch. Intern. Med. 2006;166:231-3).

The therapeutic rationale for using vardenafil in patients with Raynaud syndrome lies in the broad observation that PDE5 inhibitors exert vasodilatory properties, particularly in diseased tissue.

Dr. Caglayan declared having no financial conflicts with regard to this study, which was funded by Bayer.

ORLANDO – The phosphodiesterase type 5 inhibitor vardenafil significantly improved clinical symptoms and digital blood flow in patients with primary or secondary Raynaud syndrome in a randomized, placebo-controlled, double-blind crossover trial.

Thus, vardenafil (Levitra) appears to provide a novel, albeit off-label, therapeutic option in patients with this common, often disabling disorder for which treatment options have been limited, Dr. Evren Caglayan declared at the annual Scientific Sessions of the American Heart Association.

The study involved 53 patients with primary or secondary Raynaud syndrome who in double-blind fashion received vardenafil at 10 mg twice daily or placebo for 6 weeks. A subsequent weeklong washout period was followed crossover to 6 weeks in the other study arm.

Digital blood flow measured by laser Doppler flowmetry at room temperature after 6 weeks of continuous vardenafil therapy improved by a mean of 18.7%, compared to baseline but was unchanged during the control period, according to Dr. Caglayan of the University of Cologne (Germany).

A standardized patient questionnaire administered daily was used to assess clinical symptoms. The results were summarized as the Raynaud Condition Score. During vardenafil therapy the score declined from a baseline mean of 4.3 to 3.0 (P less than .01), mainly reflecting fewer Raynaud attacks and shorter cumulative duration of attacks.

No treatment-related adverse events occurred.

These randomized trial results confirm the favorable findings of an earlier open-label 40-patient study conducted by Dr. Caglayan and coworkers (Arch. Intern. Med. 2006;166:231-3).

The therapeutic rationale for using vardenafil in patients with Raynaud syndrome lies in the broad observation that PDE5 inhibitors exert vasodilatory properties, particularly in diseased tissue.

Dr. Caglayan declared having no financial conflicts with regard to this study, which was funded by Bayer.

ORLANDO – A history of forced sex before 18 years of age was associated with a 56% increased risk of premature cardiovascular events among women participating in the Nurses' Health Study II.

In all, 11% of the nurses enrolled in the study reported having been raped or subjected to other forms of severe forced sexual activity during childhood or adolescence. They had a 56% increased rate of acute MI or stroke before age 60, compared with those who had no history of early sexual abuse. The association was stronger for stroke than MI, Janet Wilson Rich-Edwards, Sc.D., reported at the annual scientific sessions of the American Heart Association.

The Nurses' Health Study II is the latest and far and away the largest of three studies by different research groups showing that sexually abused girls are at significantly increased cardiovascular risk as adults. It was also the most rigorous of the studies in terms of ascertainment of cardiovascular events, which were typically validated by participants’ medical records, explained Dr. Rich-Edwards of the department of epidemiology at Brigham and Women’s Hospital, Boston.

She and her colleagues were able to analyze the impact of the standard cardiovascular risk factors as mediators of the association between early sexual abuse and premature cardiovascular events. The investigators found that smoking, alcohol consumption, diabetes, adult body mass index, and hypertension accounted for 38% of the association between forced sexual activity and cardiovascular events.

"That still leaves a lot of the risk left unexplained," she noted.

This analysis of the Nurses’ Health Study II included more than 67,000 nurses, most of them white, who in 2001 completed a questionnaire on sexual and physical abuse and who were 43-60 years old in 2007. By that year, 513 cases of stroke or MI had occurred in this relatively young population.

In addition to the 11% of subjects who reported forced sex before age 18, another 22% reported sexual touching-only by an older person. Some 9% of study participants indicated that they had experienced severe physical abuse (defined as having been hit repeatedly with an object, choked, or burned) before age 18.

Nurses with a history of childhood sexual touching but no further childhood sexual abuse had a cardiovascular event rate similar to that of women with no history whatsoever of childhood sexual abuse, in an analysis that was adjusted for age, race, parental cardiovascular disease history, body type at age 5 years, and parental education.

Women with a history of rape or other forced sex before age 18 had a 56% increased relative risk when the same factors were taken into account. When rates of the standard adult cardiovascular risk factors also were factored into the analysis, this association was somewhat attenuated. However, childhood forced sexual activity remained independently associated with a highly significant 34% increased risk of cardiovascular events, compared with women who had no history of early sexual abuse.

Severe physical abuse prior to age 18 was associated with an adjusted 46% increased risk of MI or stroke in the first-round analysis. However, when the results were further adjusted for the standard adult cardiovascular risk factors, the conventional risk factors were found to account for 47% of the association between severe physical abuse and cardiovascular disease. After that adjustment, severe physical abuse was associated with a residual 23% increased risk of cardiovascular events, which wasn’t statistically significant.

"It’s clear that this association is strong ... and we need to do a better job screening for and identifying childhood sexual abuse at an early age."

The 11% rate of rape or other forced sex prior to age 18 that was reported in this study is consistent with the findings of a landmark national telephone survey of 8,000 women conducted jointly by the National Institute of Justice and the Centers for Disease Control and Prevention in 1995-1996. In that National Violence Against Women study, 18% of surveyed women reported having been raped; 22% of first rapes occurred before age 12, and another 32% occurred at age 12-17.

"I have to say, no matter how many times I see these results, the data shock me every time," Dr. Rich-Edwards commented.

An important clinical implication of the Nurses’ Health Study II findings is that childhood sexual abuse has long-lasting effects. "There’s a really long tail of chronic disease that ensues from this," she stressed.

Given that close to 40% of the increased premature cardiovascular event rate in women with a history of childhood sex abuse can be explained by elevated levels of the standard cardiovascular risk factors, risk factor modification efforts should probably be applied at an earlier age in such women. Heightened stress reactivity among women with a history of abuse might figure in their increased cardiovascular risk, and future studies will examine specific interventions, she continued.

"I think our findings are probably most relevant to adult primary care practices. In that setting, it’s really first and foremost a matter of talking about the issue of childhood abuse and helping women to normalize it to some extent.

"Physicians can point out to them that although they may have had their bodies disrespected as children, there’s a lot they can do as adults to take good care of themselves, including all of our standard cardiovascular prevention efforts," Dr. Rich-Edwards said.

AHA President-elect Donna K. Arnett, Ph.D., professor and chair of the department of epidemiology at the University of Alabama at Birmingham, had this to say about the Nurses’ Health Study II findings: "It’s clear that this association is strong, it’s associated with traditional cardiovascular risk factors, and we need to do a better job screening for and identifying childhood sexual abuse at an early age."

The study was funded by the National Institutes of Health. Dr. Rich-Edwards reported no financial conflicts.

ORLANDO – A history of forced sex before 18 years of age was associated with a 56% increased risk of premature cardiovascular events among women participating in the Nurses' Health Study II.

In all, 11% of the nurses enrolled in the study reported having been raped or subjected to other forms of severe forced sexual activity during childhood or adolescence. They had a 56% increased rate of acute MI or stroke before age 60, compared with those who had no history of early sexual abuse. The association was stronger for stroke than MI, Janet Wilson Rich-Edwards, Sc.D., reported at the annual scientific sessions of the American Heart Association.

The Nurses' Health Study II is the latest and far and away the largest of three studies by different research groups showing that sexually abused girls are at significantly increased cardiovascular risk as adults. It was also the most rigorous of the studies in terms of ascertainment of cardiovascular events, which were typically validated by participants’ medical records, explained Dr. Rich-Edwards of the department of epidemiology at Brigham and Women’s Hospital, Boston.

She and her colleagues were able to analyze the impact of the standard cardiovascular risk factors as mediators of the association between early sexual abuse and premature cardiovascular events. The investigators found that smoking, alcohol consumption, diabetes, adult body mass index, and hypertension accounted for 38% of the association between forced sexual activity and cardiovascular events.

"That still leaves a lot of the risk left unexplained," she noted.

This analysis of the Nurses’ Health Study II included more than 67,000 nurses, most of them white, who in 2001 completed a questionnaire on sexual and physical abuse and who were 43-60 years old in 2007. By that year, 513 cases of stroke or MI had occurred in this relatively young population.

In addition to the 11% of subjects who reported forced sex before age 18, another 22% reported sexual touching-only by an older person. Some 9% of study participants indicated that they had experienced severe physical abuse (defined as having been hit repeatedly with an object, choked, or burned) before age 18.

Nurses with a history of childhood sexual touching but no further childhood sexual abuse had a cardiovascular event rate similar to that of women with no history whatsoever of childhood sexual abuse, in an analysis that was adjusted for age, race, parental cardiovascular disease history, body type at age 5 years, and parental education.

Women with a history of rape or other forced sex before age 18 had a 56% increased relative risk when the same factors were taken into account. When rates of the standard adult cardiovascular risk factors also were factored into the analysis, this association was somewhat attenuated. However, childhood forced sexual activity remained independently associated with a highly significant 34% increased risk of cardiovascular events, compared with women who had no history of early sexual abuse.

Severe physical abuse prior to age 18 was associated with an adjusted 46% increased risk of MI or stroke in the first-round analysis. However, when the results were further adjusted for the standard adult cardiovascular risk factors, the conventional risk factors were found to account for 47% of the association between severe physical abuse and cardiovascular disease. After that adjustment, severe physical abuse was associated with a residual 23% increased risk of cardiovascular events, which wasn’t statistically significant.

"It’s clear that this association is strong ... and we need to do a better job screening for and identifying childhood sexual abuse at an early age."

The 11% rate of rape or other forced sex prior to age 18 that was reported in this study is consistent with the findings of a landmark national telephone survey of 8,000 women conducted jointly by the National Institute of Justice and the Centers for Disease Control and Prevention in 1995-1996. In that National Violence Against Women study, 18% of surveyed women reported having been raped; 22% of first rapes occurred before age 12, and another 32% occurred at age 12-17.

"I have to say, no matter how many times I see these results, the data shock me every time," Dr. Rich-Edwards commented.

An important clinical implication of the Nurses’ Health Study II findings is that childhood sexual abuse has long-lasting effects. "There’s a really long tail of chronic disease that ensues from this," she stressed.

Given that close to 40% of the increased premature cardiovascular event rate in women with a history of childhood sex abuse can be explained by elevated levels of the standard cardiovascular risk factors, risk factor modification efforts should probably be applied at an earlier age in such women. Heightened stress reactivity among women with a history of abuse might figure in their increased cardiovascular risk, and future studies will examine specific interventions, she continued.

"I think our findings are probably most relevant to adult primary care practices. In that setting, it’s really first and foremost a matter of talking about the issue of childhood abuse and helping women to normalize it to some extent.

"Physicians can point out to them that although they may have had their bodies disrespected as children, there’s a lot they can do as adults to take good care of themselves, including all of our standard cardiovascular prevention efforts," Dr. Rich-Edwards said.

AHA President-elect Donna K. Arnett, Ph.D., professor and chair of the department of epidemiology at the University of Alabama at Birmingham, had this to say about the Nurses’ Health Study II findings: "It’s clear that this association is strong, it’s associated with traditional cardiovascular risk factors, and we need to do a better job screening for and identifying childhood sexual abuse at an early age."

The study was funded by the National Institutes of Health. Dr. Rich-Edwards reported no financial conflicts.

ORLANDO – A history of forced sex before 18 years of age was associated with a 56% increased risk of premature cardiovascular events among women participating in the Nurses' Health Study II.

In all, 11% of the nurses enrolled in the study reported having been raped or subjected to other forms of severe forced sexual activity during childhood or adolescence. They had a 56% increased rate of acute MI or stroke before age 60, compared with those who had no history of early sexual abuse. The association was stronger for stroke than MI, Janet Wilson Rich-Edwards, Sc.D., reported at the annual scientific sessions of the American Heart Association.

The Nurses' Health Study II is the latest and far and away the largest of three studies by different research groups showing that sexually abused girls are at significantly increased cardiovascular risk as adults. It was also the most rigorous of the studies in terms of ascertainment of cardiovascular events, which were typically validated by participants’ medical records, explained Dr. Rich-Edwards of the department of epidemiology at Brigham and Women’s Hospital, Boston.

She and her colleagues were able to analyze the impact of the standard cardiovascular risk factors as mediators of the association between early sexual abuse and premature cardiovascular events. The investigators found that smoking, alcohol consumption, diabetes, adult body mass index, and hypertension accounted for 38% of the association between forced sexual activity and cardiovascular events.

"That still leaves a lot of the risk left unexplained," she noted.

This analysis of the Nurses’ Health Study II included more than 67,000 nurses, most of them white, who in 2001 completed a questionnaire on sexual and physical abuse and who were 43-60 years old in 2007. By that year, 513 cases of stroke or MI had occurred in this relatively young population.

In addition to the 11% of subjects who reported forced sex before age 18, another 22% reported sexual touching-only by an older person. Some 9% of study participants indicated that they had experienced severe physical abuse (defined as having been hit repeatedly with an object, choked, or burned) before age 18.

Nurses with a history of childhood sexual touching but no further childhood sexual abuse had a cardiovascular event rate similar to that of women with no history whatsoever of childhood sexual abuse, in an analysis that was adjusted for age, race, parental cardiovascular disease history, body type at age 5 years, and parental education.

Women with a history of rape or other forced sex before age 18 had a 56% increased relative risk when the same factors were taken into account. When rates of the standard adult cardiovascular risk factors also were factored into the analysis, this association was somewhat attenuated. However, childhood forced sexual activity remained independently associated with a highly significant 34% increased risk of cardiovascular events, compared with women who had no history of early sexual abuse.

Severe physical abuse prior to age 18 was associated with an adjusted 46% increased risk of MI or stroke in the first-round analysis. However, when the results were further adjusted for the standard adult cardiovascular risk factors, the conventional risk factors were found to account for 47% of the association between severe physical abuse and cardiovascular disease. After that adjustment, severe physical abuse was associated with a residual 23% increased risk of cardiovascular events, which wasn’t statistically significant.

"It’s clear that this association is strong ... and we need to do a better job screening for and identifying childhood sexual abuse at an early age."

The 11% rate of rape or other forced sex prior to age 18 that was reported in this study is consistent with the findings of a landmark national telephone survey of 8,000 women conducted jointly by the National Institute of Justice and the Centers for Disease Control and Prevention in 1995-1996. In that National Violence Against Women study, 18% of surveyed women reported having been raped; 22% of first rapes occurred before age 12, and another 32% occurred at age 12-17.

"I have to say, no matter how many times I see these results, the data shock me every time," Dr. Rich-Edwards commented.

An important clinical implication of the Nurses’ Health Study II findings is that childhood sexual abuse has long-lasting effects. "There’s a really long tail of chronic disease that ensues from this," she stressed.

Given that close to 40% of the increased premature cardiovascular event rate in women with a history of childhood sex abuse can be explained by elevated levels of the standard cardiovascular risk factors, risk factor modification efforts should probably be applied at an earlier age in such women. Heightened stress reactivity among women with a history of abuse might figure in their increased cardiovascular risk, and future studies will examine specific interventions, she continued.

"I think our findings are probably most relevant to adult primary care practices. In that setting, it’s really first and foremost a matter of talking about the issue of childhood abuse and helping women to normalize it to some extent.

"Physicians can point out to them that although they may have had their bodies disrespected as children, there’s a lot they can do as adults to take good care of themselves, including all of our standard cardiovascular prevention efforts," Dr. Rich-Edwards said.

AHA President-elect Donna K. Arnett, Ph.D., professor and chair of the department of epidemiology at the University of Alabama at Birmingham, had this to say about the Nurses’ Health Study II findings: "It’s clear that this association is strong, it’s associated with traditional cardiovascular risk factors, and we need to do a better job screening for and identifying childhood sexual abuse at an early age."

The study was funded by the National Institutes of Health. Dr. Rich-Edwards reported no financial conflicts.

ORLANDO – In patients with aortoiliac peripheral artery disease, adding supervised exercise to optimal medical therapy offers better treadmill walking performance than does aortoiliac stenting.

On the other hand, aortoiliac stenting plus optimal medical care results in better quality of life than does supervised exercise, according to the 6-month results of the CLEVER (Claudication vs. Endoluminal Revascularization) trial.

The CLEVER trial produced discordant results at 6 months, but also a clear signal that the combination interventions are superior to optimal medical therapy alone.

"This idea that you can go home and walk isn’t, and hasn’t been, effective," coauthor Dr. Alan Hirsch said at the annual scientific sessions of the American Heart Association.

CLEVER is the first prospective, head-to-head, comparative trial of three guideline-recommended interventions: supervised exercise, stenting, and optimal medical therapy. It is also the first trial to be conducted exclusively in patients with aortoiliac peripheral artery disease, a group generally considered ideal for stent revascularization, he said.

CLEVER randomized 111 patients to either optimal medical care, (OMC) including cilostazol (Pletal) 100 mg twice daily, plus advice about home exercise and diet with monthly coordinator contact; OMC plus supervised exercise for 1 hour thrice weekly for 26 weeks; or OMC plus aortoiliac stenting. All patients had moderate to severe claudication.

The patients averaged 64 years of age. Their baseline ankle-brachial index was 0.68, peak walking time was about 5 minutes, and claudication-onset time was 1.5 minutes.

The primary end point of change in peak walking time from baseline to 6 months was just 1.2 minutes in the OMC group, compared with 5.8 minutes in the supervised exercise group and a clinically significant 3.7 minutes in the stenting group, said Dr. Hirsch, director of the vascular medicine program at the University of Minnesota in Minneapolis. The changes were significantly different between supervised exercise and OMC (4.6 minutes), stenting and OMC (2.5 minutes), and supervised exercise and stenting (2.1 minutes).

The change in claudication-onset time from baseline to 6 months was again low with OMC at just 0.7 minutes, compared with 3 minutes with the supervised exercise and 3.6 minutes with stenting. The changes were significantly different between supervised exercise and OMC (2.2 minutes) and stenting, compared with OMC (2.9 minutes), but not between supervised exercise and stenting (0.7 minutes), again suggesting the similarity of the two interventions, he said.

Self-reported quality of life scores on the Walking Impairment Questionnaire and Peripheral Artery Questionnaire improved significantly with supervised exercise plus stenting, compared with OMC for most domains including walking distance, walking speed, stair climbing, physical limitation, social limitation, and summary score. The improvements were significantly greater with stenting than with supervised exercise for three of the four domains that were evaluated on each questionnaire.

Dr. Hirsch said the quality of life finding raises questions that CLEVER was not designed to answer, and he hoped the trial would inspire future research. Ongoing 18-month follow-up is expected to provide greater insight into the relative durability of the treatments, as well as the health economic impact.

Dr. Conte added that reimbursement for stenting is significant and not linked to outcomes, and providers and industry are therefore incentivized to provide invasive treatments.

He called for greater investment in clinical trials in PAD, more trials in intermittent claudication to clarify the best outcome measures that correlate with patient improvement in everyday life, increased pressure on the Centers for Medicare and Medicaid Services to provide reimbursement for supervised exercise programs, and more effective pharmacotherapies in intermittent claudication.

The study, which was led by Dr. Timothy Murphy, medical director of the vascular research center at Brown University in Providence, R.I., was simultaneously published online (Circulation 2011 Nov.16 [doi:10.1161/circulationaha.111.075770]).

The National Heart, Lung, and Blood Institute funded the trial, with additional support from Cordis/Johnson & Johnson, eV3, Boston Scientific, and Otsuka America. Dr. Hirsch reported grant support from Abbott Vascular, Cytokinetics, and Viromed, as well as having consulted for AstraZeneca, Merck, Novartis, and Pozen. Dr. Conte reported that he had no relevant disclosures.

ORLANDO – In patients with aortoiliac peripheral artery disease, adding supervised exercise to optimal medical therapy offers better treadmill walking performance than does aortoiliac stenting.

On the other hand, aortoiliac stenting plus optimal medical care results in better quality of life than does supervised exercise, according to the 6-month results of the CLEVER (Claudication vs. Endoluminal Revascularization) trial.

The CLEVER trial produced discordant results at 6 months, but also a clear signal that the combination interventions are superior to optimal medical therapy alone.

"This idea that you can go home and walk isn’t, and hasn’t been, effective," coauthor Dr. Alan Hirsch said at the annual scientific sessions of the American Heart Association.

CLEVER is the first prospective, head-to-head, comparative trial of three guideline-recommended interventions: supervised exercise, stenting, and optimal medical therapy. It is also the first trial to be conducted exclusively in patients with aortoiliac peripheral artery disease, a group generally considered ideal for stent revascularization, he said.

CLEVER randomized 111 patients to either optimal medical care, (OMC) including cilostazol (Pletal) 100 mg twice daily, plus advice about home exercise and diet with monthly coordinator contact; OMC plus supervised exercise for 1 hour thrice weekly for 26 weeks; or OMC plus aortoiliac stenting. All patients had moderate to severe claudication.

The patients averaged 64 years of age. Their baseline ankle-brachial index was 0.68, peak walking time was about 5 minutes, and claudication-onset time was 1.5 minutes.

The primary end point of change in peak walking time from baseline to 6 months was just 1.2 minutes in the OMC group, compared with 5.8 minutes in the supervised exercise group and a clinically significant 3.7 minutes in the stenting group, said Dr. Hirsch, director of the vascular medicine program at the University of Minnesota in Minneapolis. The changes were significantly different between supervised exercise and OMC (4.6 minutes), stenting and OMC (2.5 minutes), and supervised exercise and stenting (2.1 minutes).

The change in claudication-onset time from baseline to 6 months was again low with OMC at just 0.7 minutes, compared with 3 minutes with the supervised exercise and 3.6 minutes with stenting. The changes were significantly different between supervised exercise and OMC (2.2 minutes) and stenting, compared with OMC (2.9 minutes), but not between supervised exercise and stenting (0.7 minutes), again suggesting the similarity of the two interventions, he said.

Self-reported quality of life scores on the Walking Impairment Questionnaire and Peripheral Artery Questionnaire improved significantly with supervised exercise plus stenting, compared with OMC for most domains including walking distance, walking speed, stair climbing, physical limitation, social limitation, and summary score. The improvements were significantly greater with stenting than with supervised exercise for three of the four domains that were evaluated on each questionnaire.

Dr. Hirsch said the quality of life finding raises questions that CLEVER was not designed to answer, and he hoped the trial would inspire future research. Ongoing 18-month follow-up is expected to provide greater insight into the relative durability of the treatments, as well as the health economic impact.

Dr. Conte added that reimbursement for stenting is significant and not linked to outcomes, and providers and industry are therefore incentivized to provide invasive treatments.

He called for greater investment in clinical trials in PAD, more trials in intermittent claudication to clarify the best outcome measures that correlate with patient improvement in everyday life, increased pressure on the Centers for Medicare and Medicaid Services to provide reimbursement for supervised exercise programs, and more effective pharmacotherapies in intermittent claudication.

The study, which was led by Dr. Timothy Murphy, medical director of the vascular research center at Brown University in Providence, R.I., was simultaneously published online (Circulation 2011 Nov.16 [doi:10.1161/circulationaha.111.075770]).

The National Heart, Lung, and Blood Institute funded the trial, with additional support from Cordis/Johnson & Johnson, eV3, Boston Scientific, and Otsuka America. Dr. Hirsch reported grant support from Abbott Vascular, Cytokinetics, and Viromed, as well as having consulted for AstraZeneca, Merck, Novartis, and Pozen. Dr. Conte reported that he had no relevant disclosures.

ORLANDO – In patients with aortoiliac peripheral artery disease, adding supervised exercise to optimal medical therapy offers better treadmill walking performance than does aortoiliac stenting.

On the other hand, aortoiliac stenting plus optimal medical care results in better quality of life than does supervised exercise, according to the 6-month results of the CLEVER (Claudication vs. Endoluminal Revascularization) trial.

The CLEVER trial produced discordant results at 6 months, but also a clear signal that the combination interventions are superior to optimal medical therapy alone.

"This idea that you can go home and walk isn’t, and hasn’t been, effective," coauthor Dr. Alan Hirsch said at the annual scientific sessions of the American Heart Association.

CLEVER is the first prospective, head-to-head, comparative trial of three guideline-recommended interventions: supervised exercise, stenting, and optimal medical therapy. It is also the first trial to be conducted exclusively in patients with aortoiliac peripheral artery disease, a group generally considered ideal for stent revascularization, he said.

CLEVER randomized 111 patients to either optimal medical care, (OMC) including cilostazol (Pletal) 100 mg twice daily, plus advice about home exercise and diet with monthly coordinator contact; OMC plus supervised exercise for 1 hour thrice weekly for 26 weeks; or OMC plus aortoiliac stenting. All patients had moderate to severe claudication.

The patients averaged 64 years of age. Their baseline ankle-brachial index was 0.68, peak walking time was about 5 minutes, and claudication-onset time was 1.5 minutes.

The primary end point of change in peak walking time from baseline to 6 months was just 1.2 minutes in the OMC group, compared with 5.8 minutes in the supervised exercise group and a clinically significant 3.7 minutes in the stenting group, said Dr. Hirsch, director of the vascular medicine program at the University of Minnesota in Minneapolis. The changes were significantly different between supervised exercise and OMC (4.6 minutes), stenting and OMC (2.5 minutes), and supervised exercise and stenting (2.1 minutes).

The change in claudication-onset time from baseline to 6 months was again low with OMC at just 0.7 minutes, compared with 3 minutes with the supervised exercise and 3.6 minutes with stenting. The changes were significantly different between supervised exercise and OMC (2.2 minutes) and stenting, compared with OMC (2.9 minutes), but not between supervised exercise and stenting (0.7 minutes), again suggesting the similarity of the two interventions, he said.

Self-reported quality of life scores on the Walking Impairment Questionnaire and Peripheral Artery Questionnaire improved significantly with supervised exercise plus stenting, compared with OMC for most domains including walking distance, walking speed, stair climbing, physical limitation, social limitation, and summary score. The improvements were significantly greater with stenting than with supervised exercise for three of the four domains that were evaluated on each questionnaire.

Dr. Hirsch said the quality of life finding raises questions that CLEVER was not designed to answer, and he hoped the trial would inspire future research. Ongoing 18-month follow-up is expected to provide greater insight into the relative durability of the treatments, as well as the health economic impact.

Dr. Conte added that reimbursement for stenting is significant and not linked to outcomes, and providers and industry are therefore incentivized to provide invasive treatments.

He called for greater investment in clinical trials in PAD, more trials in intermittent claudication to clarify the best outcome measures that correlate with patient improvement in everyday life, increased pressure on the Centers for Medicare and Medicaid Services to provide reimbursement for supervised exercise programs, and more effective pharmacotherapies in intermittent claudication.

The study, which was led by Dr. Timothy Murphy, medical director of the vascular research center at Brown University in Providence, R.I., was simultaneously published online (Circulation 2011 Nov.16 [doi:10.1161/circulationaha.111.075770]).

The National Heart, Lung, and Blood Institute funded the trial, with additional support from Cordis/Johnson & Johnson, eV3, Boston Scientific, and Otsuka America. Dr. Hirsch reported grant support from Abbott Vascular, Cytokinetics, and Viromed, as well as having consulted for AstraZeneca, Merck, Novartis, and Pozen. Dr. Conte reported that he had no relevant disclosures.

ORLANDO – A 12-week treatment regimen with a purified formulation of fish oil led to a greater-than-20% reduction of elevated triglyceride levels, as well as other favorable lipid changes, in a phase III, randomized, placebo-controlled trial in about 700 patients.

"AMR101, pure eicosapentaenoic acid, at both 4 g/day and 2 g/day significantly reduced triglyceride levels in statin-treated patients with optimized low-density lipoprotein cholesterol levels and persistently elevated triglyceride levels," Dr. Christie M. Ballantyne said at the annual scientific sessions of the American Heart Association. The results he reported from the ANCHOR trial came from a group of 702 patients who had high cardiovascular disease risk and were on "optimized" statin therapy, with an LDL cholesterol level of 100 mg/dL or less, but with a triglyceride level of 200-500 mg/dL.

Although the highest dosage of AMR101 tested (4 g/day) produced an average 22% reduction in triglyceride level beyond the placebo effect after 12 weeks of treatment, the clinical benefit from this triglyceride reduction remains uncertain until results accrue from a longer-term study that has clinical end points but is only now starting, he added.

"The key issue is, What does this mean for outcomes?" said Dr. Ballantyne, professor of medicine and pediatrics and chief of the section of atherosclerosis and vascular medicine at Baylor College of Medicine in Houston. "Omega-3 fatty acids have proven safety, but the question is, What will be the event reduction? There was prior evidence for efficacy in ... JELIS [Japan EPA Lipid Intervention Study]. I think the odds are higher for this working than for many other treatments," he said in an interview. But, he acknowledged, "no one has ever done a trial on patients with elevated triglycerides."

JELIS enrolled more than 18,000 men and postmenopausal women, both with and without documented coronary artery disease, who had a total cholesterol level of at least 6.5 mmol/L (251 mg/dL), and an LDL cholesterol level of at least 4.4 mmol/L (171 mg/dL). JELIS randomized patients to treatment with either a statin alone or a statin plus 1.8 g/day eicosapentaenoic acid (EPA), purified from omega-3 fatty acids in fish oil. After an average follow-up of 4.6 years, people in the combined statin-plus-EPA group had a 2.8% incidence of a major coronary event, compared with a 3.5% rate in those who were treated with a statin only, a 19% relative risk reduction that was statistically significant (Lancet 2007;369:1090-8). According to Dr. Ballantyne and others, the JELIS result remains the only evidence documenting that treatment with EPA can reduce the incidence of coronary events, although JELIS did not specifically enroll patients with elevated triglyceride levels at baseline.

"There is no evidence" that lowering triglycerides cuts coronary events, agreed Dr. Eliot A. Brinton, director of atherometabolic research at the Utah Foundation for Biomedical Research in Salt Lake City. "Results from five fibrate treatment trials were all suggestive that lowering triglycerides led to reduced events. And the JELIS results showed clinical benefit with fish oil and greater benefit in people who entered with high triglycerides and low levels of HDL cholesterol. The EPA [that was] used in JELIS was essentially the same drug as AMR101," a highly purified form of EPA, Dr. Brinton said in an interview. "But we won’t know what AMR101 will do for events until we do a study," added Dr. Brinton, who is on the steering committee for the AMR101 clinical trial scheduled to soon begin.

"I think we have a very good chance of showing benefit. It’s very exciting. If any drug can show a statistically significant benefit on top of a statin, it will be a huge step forward," Dr. Brinton commented.

In September, Amarin, the company developing AMR101, announced that it had filed a New Drug Application with the Food and Drug Administration seeking marketing approval for AMR101 for treating elevated triglyceride levels, based on both the ANCHOR results and the results of a similarly designed study, the MARINE (Multicenter, Placebo-Controlled, Randomized, Double-Blind, 12-Week Study With an Open-Label Extension) trial, which randomized 229 patients with fasting triglyceride levels of at least 500 mg/dL (average baseline level, about 680 mg/dL) to treatment with either the 4-g/day or 2-g/day dosages of AMR101 or placebo. Results from the MARINE study, published in September, showed that after 12 weeks the 4-g/day dosage of AMR101 led to an average 45% placebo-corrected cut in triglycerides (Am. J. Cardiol. 2011;108:682-90).

The clinical end point trial – REDUCE-IT (Reduction of Cardiovascular Events With EPA–Intervention Trial) – that Amarin plans for AMR101 will enroll about 8,000 patients with elevated triglycerides and will last for 6 years. However, Amarin announced last August that it arranged a Special Protocol Assessment with the FDA that may allow the FDA to approve AMR101 for treating the mixed dyslipidemia patients who are enrolled in ANCHOR before the REDUCE-IT trial is completed.

The ANCHOR trial ran at 97 U.S. sites, and enrolled patients who were, on average, 61 years old, 61% of whom were men. Their average body mass index was 33 kg/m² and 73% had diabetes. Some 63% were on a "medium" efficacy statin regimen, 30% were on a "high" efficacy regimen, and 7% were on a "low" efficacy statin regimen. The study’s primary end point was the change in triglyceride level, compared with placebo treatment, and the secondary end points included the change in LDL cholesterol, compared with placebo.

The 4-g/day dosage produced an average placebo-corrected 21.5% reduction in triglyceride level, an average 6.2% cut in LDL cholesterol, an average 13.6% decrease in non-HDL cholesterol, and an average 4.9% reduction in HDL cholesterol, all statistically significant changes. The 2-g/day dosage produced smaller placebo-corrected reductions, including a 10.1% cut in triglycerides that was statistically significant, and a nonsignificant 3.6% decrease in LDL cholesterol. The results also showed that triglyceride reductions were larger in patients who started with higher triglyceride levels at baseline, and in patients on higher-efficacy statin regimens, Dr. Ballantyne reported.

Both EPA dosages tested were well tolerated, with adverse effects that were mild to moderate and most appearing to be unrelated to the study medication. "In general, omega-3 fatty acids have been very well tolerated and very safe in numerous studies over many years," Dr. Ballantyne said. "GI tolerability was quite good, but the taste issue remains," he said.

Dr. Ballantyne said that he currently prescribes EPA to some of his patients. He prefers to prescribe Lovaza (a brand-name, prescription-only formulation of omega-3 fatty acid ethyl esters that contains both EPA and docosahexaenoic acid) because it is a "high quality agent," he said in an interview. "If a patient cannot afford that, we give them tips on how to purchase high-quality supplement" formulations of omega-3 fatty acids, he added.

ANCHOR was sponsored by Amarin, the company developing AMR101. Dr. Ballantyne said that he has been a consultant for Amarin and has consulted for, received honoraria from, and/or been a speaker for numerous other pharmaceutical companies. Dr. Brinton said that he has been a consultant to Amarin and has also consulted for and/or been a speaker for several other firms.

ORLANDO – A 12-week treatment regimen with a purified formulation of fish oil led to a greater-than-20% reduction of elevated triglyceride levels, as well as other favorable lipid changes, in a phase III, randomized, placebo-controlled trial in about 700 patients.

"AMR101, pure eicosapentaenoic acid, at both 4 g/day and 2 g/day significantly reduced triglyceride levels in statin-treated patients with optimized low-density lipoprotein cholesterol levels and persistently elevated triglyceride levels," Dr. Christie M. Ballantyne said at the annual scientific sessions of the American Heart Association. The results he reported from the ANCHOR trial came from a group of 702 patients who had high cardiovascular disease risk and were on "optimized" statin therapy, with an LDL cholesterol level of 100 mg/dL or less, but with a triglyceride level of 200-500 mg/dL.

Although the highest dosage of AMR101 tested (4 g/day) produced an average 22% reduction in triglyceride level beyond the placebo effect after 12 weeks of treatment, the clinical benefit from this triglyceride reduction remains uncertain until results accrue from a longer-term study that has clinical end points but is only now starting, he added.

"The key issue is, What does this mean for outcomes?" said Dr. Ballantyne, professor of medicine and pediatrics and chief of the section of atherosclerosis and vascular medicine at Baylor College of Medicine in Houston. "Omega-3 fatty acids have proven safety, but the question is, What will be the event reduction? There was prior evidence for efficacy in ... JELIS [Japan EPA Lipid Intervention Study]. I think the odds are higher for this working than for many other treatments," he said in an interview. But, he acknowledged, "no one has ever done a trial on patients with elevated triglycerides."

JELIS enrolled more than 18,000 men and postmenopausal women, both with and without documented coronary artery disease, who had a total cholesterol level of at least 6.5 mmol/L (251 mg/dL), and an LDL cholesterol level of at least 4.4 mmol/L (171 mg/dL). JELIS randomized patients to treatment with either a statin alone or a statin plus 1.8 g/day eicosapentaenoic acid (EPA), purified from omega-3 fatty acids in fish oil. After an average follow-up of 4.6 years, people in the combined statin-plus-EPA group had a 2.8% incidence of a major coronary event, compared with a 3.5% rate in those who were treated with a statin only, a 19% relative risk reduction that was statistically significant (Lancet 2007;369:1090-8). According to Dr. Ballantyne and others, the JELIS result remains the only evidence documenting that treatment with EPA can reduce the incidence of coronary events, although JELIS did not specifically enroll patients with elevated triglyceride levels at baseline.

"There is no evidence" that lowering triglycerides cuts coronary events, agreed Dr. Eliot A. Brinton, director of atherometabolic research at the Utah Foundation for Biomedical Research in Salt Lake City. "Results from five fibrate treatment trials were all suggestive that lowering triglycerides led to reduced events. And the JELIS results showed clinical benefit with fish oil and greater benefit in people who entered with high triglycerides and low levels of HDL cholesterol. The EPA [that was] used in JELIS was essentially the same drug as AMR101," a highly purified form of EPA, Dr. Brinton said in an interview. "But we won’t know what AMR101 will do for events until we do a study," added Dr. Brinton, who is on the steering committee for the AMR101 clinical trial scheduled to soon begin.

"I think we have a very good chance of showing benefit. It’s very exciting. If any drug can show a statistically significant benefit on top of a statin, it will be a huge step forward," Dr. Brinton commented.

In September, Amarin, the company developing AMR101, announced that it had filed a New Drug Application with the Food and Drug Administration seeking marketing approval for AMR101 for treating elevated triglyceride levels, based on both the ANCHOR results and the results of a similarly designed study, the MARINE (Multicenter, Placebo-Controlled, Randomized, Double-Blind, 12-Week Study With an Open-Label Extension) trial, which randomized 229 patients with fasting triglyceride levels of at least 500 mg/dL (average baseline level, about 680 mg/dL) to treatment with either the 4-g/day or 2-g/day dosages of AMR101 or placebo. Results from the MARINE study, published in September, showed that after 12 weeks the 4-g/day dosage of AMR101 led to an average 45% placebo-corrected cut in triglycerides (Am. J. Cardiol. 2011;108:682-90).

The clinical end point trial – REDUCE-IT (Reduction of Cardiovascular Events With EPA–Intervention Trial) – that Amarin plans for AMR101 will enroll about 8,000 patients with elevated triglycerides and will last for 6 years. However, Amarin announced last August that it arranged a Special Protocol Assessment with the FDA that may allow the FDA to approve AMR101 for treating the mixed dyslipidemia patients who are enrolled in ANCHOR before the REDUCE-IT trial is completed.

The ANCHOR trial ran at 97 U.S. sites, and enrolled patients who were, on average, 61 years old, 61% of whom were men. Their average body mass index was 33 kg/m² and 73% had diabetes. Some 63% were on a "medium" efficacy statin regimen, 30% were on a "high" efficacy regimen, and 7% were on a "low" efficacy statin regimen. The study’s primary end point was the change in triglyceride level, compared with placebo treatment, and the secondary end points included the change in LDL cholesterol, compared with placebo.

The 4-g/day dosage produced an average placebo-corrected 21.5% reduction in triglyceride level, an average 6.2% cut in LDL cholesterol, an average 13.6% decrease in non-HDL cholesterol, and an average 4.9% reduction in HDL cholesterol, all statistically significant changes. The 2-g/day dosage produced smaller placebo-corrected reductions, including a 10.1% cut in triglycerides that was statistically significant, and a nonsignificant 3.6% decrease in LDL cholesterol. The results also showed that triglyceride reductions were larger in patients who started with higher triglyceride levels at baseline, and in patients on higher-efficacy statin regimens, Dr. Ballantyne reported.

Both EPA dosages tested were well tolerated, with adverse effects that were mild to moderate and most appearing to be unrelated to the study medication. "In general, omega-3 fatty acids have been very well tolerated and very safe in numerous studies over many years," Dr. Ballantyne said. "GI tolerability was quite good, but the taste issue remains," he said.

Dr. Ballantyne said that he currently prescribes EPA to some of his patients. He prefers to prescribe Lovaza (a brand-name, prescription-only formulation of omega-3 fatty acid ethyl esters that contains both EPA and docosahexaenoic acid) because it is a "high quality agent," he said in an interview. "If a patient cannot afford that, we give them tips on how to purchase high-quality supplement" formulations of omega-3 fatty acids, he added.

ANCHOR was sponsored by Amarin, the company developing AMR101. Dr. Ballantyne said that he has been a consultant for Amarin and has consulted for, received honoraria from, and/or been a speaker for numerous other pharmaceutical companies. Dr. Brinton said that he has been a consultant to Amarin and has also consulted for and/or been a speaker for several other firms.

ORLANDO – A 12-week treatment regimen with a purified formulation of fish oil led to a greater-than-20% reduction of elevated triglyceride levels, as well as other favorable lipid changes, in a phase III, randomized, placebo-controlled trial in about 700 patients.

"AMR101, pure eicosapentaenoic acid, at both 4 g/day and 2 g/day significantly reduced triglyceride levels in statin-treated patients with optimized low-density lipoprotein cholesterol levels and persistently elevated triglyceride levels," Dr. Christie M. Ballantyne said at the annual scientific sessions of the American Heart Association. The results he reported from the ANCHOR trial came from a group of 702 patients who had high cardiovascular disease risk and were on "optimized" statin therapy, with an LDL cholesterol level of 100 mg/dL or less, but with a triglyceride level of 200-500 mg/dL.

Although the highest dosage of AMR101 tested (4 g/day) produced an average 22% reduction in triglyceride level beyond the placebo effect after 12 weeks of treatment, the clinical benefit from this triglyceride reduction remains uncertain until results accrue from a longer-term study that has clinical end points but is only now starting, he added.

"The key issue is, What does this mean for outcomes?" said Dr. Ballantyne, professor of medicine and pediatrics and chief of the section of atherosclerosis and vascular medicine at Baylor College of Medicine in Houston. "Omega-3 fatty acids have proven safety, but the question is, What will be the event reduction? There was prior evidence for efficacy in ... JELIS [Japan EPA Lipid Intervention Study]. I think the odds are higher for this working than for many other treatments," he said in an interview. But, he acknowledged, "no one has ever done a trial on patients with elevated triglycerides."

JELIS enrolled more than 18,000 men and postmenopausal women, both with and without documented coronary artery disease, who had a total cholesterol level of at least 6.5 mmol/L (251 mg/dL), and an LDL cholesterol level of at least 4.4 mmol/L (171 mg/dL). JELIS randomized patients to treatment with either a statin alone or a statin plus 1.8 g/day eicosapentaenoic acid (EPA), purified from omega-3 fatty acids in fish oil. After an average follow-up of 4.6 years, people in the combined statin-plus-EPA group had a 2.8% incidence of a major coronary event, compared with a 3.5% rate in those who were treated with a statin only, a 19% relative risk reduction that was statistically significant (Lancet 2007;369:1090-8). According to Dr. Ballantyne and others, the JELIS result remains the only evidence documenting that treatment with EPA can reduce the incidence of coronary events, although JELIS did not specifically enroll patients with elevated triglyceride levels at baseline.

"There is no evidence" that lowering triglycerides cuts coronary events, agreed Dr. Eliot A. Brinton, director of atherometabolic research at the Utah Foundation for Biomedical Research in Salt Lake City. "Results from five fibrate treatment trials were all suggestive that lowering triglycerides led to reduced events. And the JELIS results showed clinical benefit with fish oil and greater benefit in people who entered with high triglycerides and low levels of HDL cholesterol. The EPA [that was] used in JELIS was essentially the same drug as AMR101," a highly purified form of EPA, Dr. Brinton said in an interview. "But we won’t know what AMR101 will do for events until we do a study," added Dr. Brinton, who is on the steering committee for the AMR101 clinical trial scheduled to soon begin.

"I think we have a very good chance of showing benefit. It’s very exciting. If any drug can show a statistically significant benefit on top of a statin, it will be a huge step forward," Dr. Brinton commented.

In September, Amarin, the company developing AMR101, announced that it had filed a New Drug Application with the Food and Drug Administration seeking marketing approval for AMR101 for treating elevated triglyceride levels, based on both the ANCHOR results and the results of a similarly designed study, the MARINE (Multicenter, Placebo-Controlled, Randomized, Double-Blind, 12-Week Study With an Open-Label Extension) trial, which randomized 229 patients with fasting triglyceride levels of at least 500 mg/dL (average baseline level, about 680 mg/dL) to treatment with either the 4-g/day or 2-g/day dosages of AMR101 or placebo. Results from the MARINE study, published in September, showed that after 12 weeks the 4-g/day dosage of AMR101 led to an average 45% placebo-corrected cut in triglycerides (Am. J. Cardiol. 2011;108:682-90).

The clinical end point trial – REDUCE-IT (Reduction of Cardiovascular Events With EPA–Intervention Trial) – that Amarin plans for AMR101 will enroll about 8,000 patients with elevated triglycerides and will last for 6 years. However, Amarin announced last August that it arranged a Special Protocol Assessment with the FDA that may allow the FDA to approve AMR101 for treating the mixed dyslipidemia patients who are enrolled in ANCHOR before the REDUCE-IT trial is completed.

The ANCHOR trial ran at 97 U.S. sites, and enrolled patients who were, on average, 61 years old, 61% of whom were men. Their average body mass index was 33 kg/m² and 73% had diabetes. Some 63% were on a "medium" efficacy statin regimen, 30% were on a "high" efficacy regimen, and 7% were on a "low" efficacy statin regimen. The study’s primary end point was the change in triglyceride level, compared with placebo treatment, and the secondary end points included the change in LDL cholesterol, compared with placebo.

The 4-g/day dosage produced an average placebo-corrected 21.5% reduction in triglyceride level, an average 6.2% cut in LDL cholesterol, an average 13.6% decrease in non-HDL cholesterol, and an average 4.9% reduction in HDL cholesterol, all statistically significant changes. The 2-g/day dosage produced smaller placebo-corrected reductions, including a 10.1% cut in triglycerides that was statistically significant, and a nonsignificant 3.6% decrease in LDL cholesterol. The results also showed that triglyceride reductions were larger in patients who started with higher triglyceride levels at baseline, and in patients on higher-efficacy statin regimens, Dr. Ballantyne reported.

Both EPA dosages tested were well tolerated, with adverse effects that were mild to moderate and most appearing to be unrelated to the study medication. "In general, omega-3 fatty acids have been very well tolerated and very safe in numerous studies over many years," Dr. Ballantyne said. "GI tolerability was quite good, but the taste issue remains," he said.

Dr. Ballantyne said that he currently prescribes EPA to some of his patients. He prefers to prescribe Lovaza (a brand-name, prescription-only formulation of omega-3 fatty acid ethyl esters that contains both EPA and docosahexaenoic acid) because it is a "high quality agent," he said in an interview. "If a patient cannot afford that, we give them tips on how to purchase high-quality supplement" formulations of omega-3 fatty acids, he added.

ANCHOR was sponsored by Amarin, the company developing AMR101. Dr. Ballantyne said that he has been a consultant for Amarin and has consulted for, received honoraria from, and/or been a speaker for numerous other pharmaceutical companies. Dr. Brinton said that he has been a consultant to Amarin and has also consulted for and/or been a speaker for several other firms.

ORLANDO – After 100 years as America’s No. 1 killer, the combination of coronary disease and stroke is about to fall below cancer as the nation’s top cause of mortality.

The changeover occurred 3 years ago, in 2008, for the approximately 1.9 million adults enrolled in Kaiser Permanente of Northern California, and the ascendancy of cancer over coronary disease and stroke will happen throughout the United States sometime before the end of this decade, Dr. Stephen Sidney said while presenting a poster at the annual scientific sessions of the American Heart Association.*

The main driver of this shift is the huge progress made in curbing coronary and stroke deaths during the past half century, especially since 2000, said Dr. Sidney, associate director for clinical research of Kaiser Permanente of Northern California in Oakland.

"It’s a huge public health success from multifactorial interventions for primary prevention and secondary prevention," he said in an interview. During the 2000s alone, coronary disease mortality among Kaiser adults at least 30 years old fell by 27%, and stroke mortality plunged by 42%. In contrast, cancer mortality among adult members of Kaiser Permanente of Northern California dropped by 11%. "We’ve made huge progress and policy makers need to start thinking that [coronary disease and stroke] are not the biggest causes of mortality," he said.

Coronary disease first topped America’s killer list in 1910 and stayed in place for decades, but then started a trajectory of substantial decline by about 1970, he said. As recently as 2000, among adult members of Kaiser Permanente of Northern California, coronary disease alone accounted for about 300 deaths per 100,000 person-years, putting it on par with cancer, whereas coronary disease plus stroke together sat atop the killer list with a rate of about 400 deaths per 100,000 person-years in 2000. By 2008, coronary deaths alone had fallen to 200 per 100,000 person-years, while coronary and stroke deaths together dropped just below the 270 per 100,000 person-years level that cancer reached that year.

Although the crossing of the cardiovascular and cancer mortality rates has not yet happened throughout the United States, similar trends are at work. During 2000-2007, the gap in age-adjusted death rates between coronary disease and cancer fell by 88%, he said.

Dr. Sidney cited two Kaiser programs begun during the 2000s that he believes led to the big cardiovascular mortality drop of that era.

One was a concerted effort to diagnose and treat hypertension, a prime cardiovascular-event risk factor. As recently as 2001, only 38% of hypertensive patients in Kaiser Permanente of Northern California had their blood pressure controlled. Kaiser physicians perceived this as a major shortcoming, and launched a campaign to address it, so that by 2010 the percentage of controlled hypertensives had risen to 80%, he said.

The other initiative was a Kaiser program to treat all patients with coronary disease, cerebrovascular disease, peripheral arterial disease, chronic kidney disease, and those with an abdominal aortic aneurysm with aspirin, a statin, and an angiotensin-converting enzyme inhibitor.

Parallel efforts to bring the cancer rate down are much harder, because cancer is "a diverse set of etiologically distinct diseases with a myriad of interventions, making implementation of population-based approaches more complex, resulting in a slower rate of mortality decline," Dr. Sidney said in his poster.

Dr. Sidney said that he had no disclosures.

*Correction, 12/16/2011: An earlier version of this story misstated the number of adults enrolled in Kaiser Permanente of Northern California.

ORLANDO – After 100 years as America’s No. 1 killer, the combination of coronary disease and stroke is about to fall below cancer as the nation’s top cause of mortality.

The changeover occurred 3 years ago, in 2008, for the approximately 1.9 million adults enrolled in Kaiser Permanente of Northern California, and the ascendancy of cancer over coronary disease and stroke will happen throughout the United States sometime before the end of this decade, Dr. Stephen Sidney said while presenting a poster at the annual scientific sessions of the American Heart Association.*

The main driver of this shift is the huge progress made in curbing coronary and stroke deaths during the past half century, especially since 2000, said Dr. Sidney, associate director for clinical research of Kaiser Permanente of Northern California in Oakland.

"It’s a huge public health success from multifactorial interventions for primary prevention and secondary prevention," he said in an interview. During the 2000s alone, coronary disease mortality among Kaiser adults at least 30 years old fell by 27%, and stroke mortality plunged by 42%. In contrast, cancer mortality among adult members of Kaiser Permanente of Northern California dropped by 11%. "We’ve made huge progress and policy makers need to start thinking that [coronary disease and stroke] are not the biggest causes of mortality," he said.

Coronary disease first topped America’s killer list in 1910 and stayed in place for decades, but then started a trajectory of substantial decline by about 1970, he said. As recently as 2000, among adult members of Kaiser Permanente of Northern California, coronary disease alone accounted for about 300 deaths per 100,000 person-years, putting it on par with cancer, whereas coronary disease plus stroke together sat atop the killer list with a rate of about 400 deaths per 100,000 person-years in 2000. By 2008, coronary deaths alone had fallen to 200 per 100,000 person-years, while coronary and stroke deaths together dropped just below the 270 per 100,000 person-years level that cancer reached that year.

Although the crossing of the cardiovascular and cancer mortality rates has not yet happened throughout the United States, similar trends are at work. During 2000-2007, the gap in age-adjusted death rates between coronary disease and cancer fell by 88%, he said.

Dr. Sidney cited two Kaiser programs begun during the 2000s that he believes led to the big cardiovascular mortality drop of that era.

One was a concerted effort to diagnose and treat hypertension, a prime cardiovascular-event risk factor. As recently as 2001, only 38% of hypertensive patients in Kaiser Permanente of Northern California had their blood pressure controlled. Kaiser physicians perceived this as a major shortcoming, and launched a campaign to address it, so that by 2010 the percentage of controlled hypertensives had risen to 80%, he said.

The other initiative was a Kaiser program to treat all patients with coronary disease, cerebrovascular disease, peripheral arterial disease, chronic kidney disease, and those with an abdominal aortic aneurysm with aspirin, a statin, and an angiotensin-converting enzyme inhibitor.

Parallel efforts to bring the cancer rate down are much harder, because cancer is "a diverse set of etiologically distinct diseases with a myriad of interventions, making implementation of population-based approaches more complex, resulting in a slower rate of mortality decline," Dr. Sidney said in his poster.

Dr. Sidney said that he had no disclosures.

*Correction, 12/16/2011: An earlier version of this story misstated the number of adults enrolled in Kaiser Permanente of Northern California.

ORLANDO – After 100 years as America’s No. 1 killer, the combination of coronary disease and stroke is about to fall below cancer as the nation’s top cause of mortality.

The changeover occurred 3 years ago, in 2008, for the approximately 1.9 million adults enrolled in Kaiser Permanente of Northern California, and the ascendancy of cancer over coronary disease and stroke will happen throughout the United States sometime before the end of this decade, Dr. Stephen Sidney said while presenting a poster at the annual scientific sessions of the American Heart Association.*

The main driver of this shift is the huge progress made in curbing coronary and stroke deaths during the past half century, especially since 2000, said Dr. Sidney, associate director for clinical research of Kaiser Permanente of Northern California in Oakland.

"It’s a huge public health success from multifactorial interventions for primary prevention and secondary prevention," he said in an interview. During the 2000s alone, coronary disease mortality among Kaiser adults at least 30 years old fell by 27%, and stroke mortality plunged by 42%. In contrast, cancer mortality among adult members of Kaiser Permanente of Northern California dropped by 11%. "We’ve made huge progress and policy makers need to start thinking that [coronary disease and stroke] are not the biggest causes of mortality," he said.

Coronary disease first topped America’s killer list in 1910 and stayed in place for decades, but then started a trajectory of substantial decline by about 1970, he said. As recently as 2000, among adult members of Kaiser Permanente of Northern California, coronary disease alone accounted for about 300 deaths per 100,000 person-years, putting it on par with cancer, whereas coronary disease plus stroke together sat atop the killer list with a rate of about 400 deaths per 100,000 person-years in 2000. By 2008, coronary deaths alone had fallen to 200 per 100,000 person-years, while coronary and stroke deaths together dropped just below the 270 per 100,000 person-years level that cancer reached that year.

Although the crossing of the cardiovascular and cancer mortality rates has not yet happened throughout the United States, similar trends are at work. During 2000-2007, the gap in age-adjusted death rates between coronary disease and cancer fell by 88%, he said.

Dr. Sidney cited two Kaiser programs begun during the 2000s that he believes led to the big cardiovascular mortality drop of that era.

One was a concerted effort to diagnose and treat hypertension, a prime cardiovascular-event risk factor. As recently as 2001, only 38% of hypertensive patients in Kaiser Permanente of Northern California had their blood pressure controlled. Kaiser physicians perceived this as a major shortcoming, and launched a campaign to address it, so that by 2010 the percentage of controlled hypertensives had risen to 80%, he said.

The other initiative was a Kaiser program to treat all patients with coronary disease, cerebrovascular disease, peripheral arterial disease, chronic kidney disease, and those with an abdominal aortic aneurysm with aspirin, a statin, and an angiotensin-converting enzyme inhibitor.

Parallel efforts to bring the cancer rate down are much harder, because cancer is "a diverse set of etiologically distinct diseases with a myriad of interventions, making implementation of population-based approaches more complex, resulting in a slower rate of mortality decline," Dr. Sidney said in his poster.

Dr. Sidney said that he had no disclosures.

*Correction, 12/16/2011: An earlier version of this story misstated the number of adults enrolled in Kaiser Permanente of Northern California.