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American Heart Association (AHA): Scientific Sessions 2013
Statin in Childhood Reduces CHD Risk in Familial Hypercholesterolemia
DALLAS – Roughly 10 years after going on statin therapy as children or adolescents, a group of Dutch patients with familial hypercholesterolemia already has a significantly lower cardiovascular event rate than their affected parents did at the same age.
"Statin therapy in childhood seems to be effective in reducing CHD [coronary heart disease] risk in individuals with FH [familial hypercholesterolemia], although longer follow-up is needed to confirm these results," Dr. Marjet J.A.M. Braamskamp declared at the American Heart Association scientific sessions.
The 214 Dutch youths with FH started on statin therapy at age 8-18 years as part of a randomized clinical trial. None has experienced a cardiovascular event by age 30. In contrast, their affected parents, for whom statins weren’t available until they were well into adulthood, already had a 7% CHD event rate by age 30, a statistically significant difference, reported Dr. Braamskamp of the Academic Medical Center, Amsterdam.
In an interview, she said the plan is to continue to follow this cohort of young adults who started statin therapy in childhood at least until age 50. By that age, 55% of their fathers with FH and 24% of their mothers with FH had known CHD. While none of the FH mothers died of CHD before age 60, 16% of the FH fathers did, at an average age of 35.9 years.
Current European and American guidelines recommend statin therapy starting at age 8 or 10 years in children with the molecular or clinical diagnosis of FH and elevated cholesterol levels. Those guidelines were issued based upon recognition that children with FH have elevated cholesterol levels from birth onward, coupled with evidence from short-term randomized trials demonstrating that statins are safe and effective for lipid-lowering in such patients. The Dutch follow-up study provides evidence to suggest this early-treatment strategy also pays off in terms of reduced CHD risk.
The study was supported by the Dutch Heart Foundation. Dr. Braamskamp reported having no financial conflicts.
DALLAS – Roughly 10 years after going on statin therapy as children or adolescents, a group of Dutch patients with familial hypercholesterolemia already has a significantly lower cardiovascular event rate than their affected parents did at the same age.
"Statin therapy in childhood seems to be effective in reducing CHD [coronary heart disease] risk in individuals with FH [familial hypercholesterolemia], although longer follow-up is needed to confirm these results," Dr. Marjet J.A.M. Braamskamp declared at the American Heart Association scientific sessions.
The 214 Dutch youths with FH started on statin therapy at age 8-18 years as part of a randomized clinical trial. None has experienced a cardiovascular event by age 30. In contrast, their affected parents, for whom statins weren’t available until they were well into adulthood, already had a 7% CHD event rate by age 30, a statistically significant difference, reported Dr. Braamskamp of the Academic Medical Center, Amsterdam.
In an interview, she said the plan is to continue to follow this cohort of young adults who started statin therapy in childhood at least until age 50. By that age, 55% of their fathers with FH and 24% of their mothers with FH had known CHD. While none of the FH mothers died of CHD before age 60, 16% of the FH fathers did, at an average age of 35.9 years.
Current European and American guidelines recommend statin therapy starting at age 8 or 10 years in children with the molecular or clinical diagnosis of FH and elevated cholesterol levels. Those guidelines were issued based upon recognition that children with FH have elevated cholesterol levels from birth onward, coupled with evidence from short-term randomized trials demonstrating that statins are safe and effective for lipid-lowering in such patients. The Dutch follow-up study provides evidence to suggest this early-treatment strategy also pays off in terms of reduced CHD risk.
The study was supported by the Dutch Heart Foundation. Dr. Braamskamp reported having no financial conflicts.
DALLAS – Roughly 10 years after going on statin therapy as children or adolescents, a group of Dutch patients with familial hypercholesterolemia already has a significantly lower cardiovascular event rate than their affected parents did at the same age.
"Statin therapy in childhood seems to be effective in reducing CHD [coronary heart disease] risk in individuals with FH [familial hypercholesterolemia], although longer follow-up is needed to confirm these results," Dr. Marjet J.A.M. Braamskamp declared at the American Heart Association scientific sessions.
The 214 Dutch youths with FH started on statin therapy at age 8-18 years as part of a randomized clinical trial. None has experienced a cardiovascular event by age 30. In contrast, their affected parents, for whom statins weren’t available until they were well into adulthood, already had a 7% CHD event rate by age 30, a statistically significant difference, reported Dr. Braamskamp of the Academic Medical Center, Amsterdam.
In an interview, she said the plan is to continue to follow this cohort of young adults who started statin therapy in childhood at least until age 50. By that age, 55% of their fathers with FH and 24% of their mothers with FH had known CHD. While none of the FH mothers died of CHD before age 60, 16% of the FH fathers did, at an average age of 35.9 years.
Current European and American guidelines recommend statin therapy starting at age 8 or 10 years in children with the molecular or clinical diagnosis of FH and elevated cholesterol levels. Those guidelines were issued based upon recognition that children with FH have elevated cholesterol levels from birth onward, coupled with evidence from short-term randomized trials demonstrating that statins are safe and effective for lipid-lowering in such patients. The Dutch follow-up study provides evidence to suggest this early-treatment strategy also pays off in terms of reduced CHD risk.
The study was supported by the Dutch Heart Foundation. Dr. Braamskamp reported having no financial conflicts.
AT THE AHA SCIENTIFIC SESSIONS
Body Fat and Cardiovascular Risk: Location, Location, Location!
DALLAS – It’s not obesity per se that affects cardiovascular risk, it’s where that excess body fat is stored, according to the results of a novel adipose tissue–imaging study.
Excess visceral adipose tissue is independently associated with increased risk of developing cardiovascular disease. In contrast, increased lower body subcutaneous adipose tissue – that is, fat around the hips and a big butt – actually seems to protect against cardiovascular disease, Dr. Ian J. Neeland reported at the American Heart Association scientific sessions.
He presented an analysis of 972 obese participants in the Dallas Heart Study with a mean age of 44 years at enrollment and no baseline cardiovascular disease. All underwent dual-energy x-ray absorptiometry and MRI assessment of their body fat distribution, focusing on the visceral, abdominal subcutaneous, and lower body subcutaneous adipose tissue depots. Participants were then followed prospectively for a median 8.1 years, during which 91 cardiovascular events occurred in 68 subjects.
The impetus for the adipose tissue imaging study was the researchers’ recognition that obesity is a heterogeneous disorder.
"Currently, we know that obesity is associated with incident cardiovascular disease at a general population level. However, body mass index alone is really an inadequate marker of risk among the obese. Many individuals with even high BMIs do not develop cardiovascular disease. Marked abdominal obesity is a stronger predictor of cardiovascular disease but still lacks the necessary specificity. So there’s really a clinical need for tools to differentiate obese individuals who will develop cardiovascular disease from those who will be free of cardiovascular disease for their lifetime," explained Dr. Neeland, a fellow in cardiovascular medicine at the University of Texas Southwestern Medical Center, Dallas.
In a multivariate analysis adjusted for age, sex, race, and the conventional cardiovascular risk factors, each 1–standard deviation increase in visceral adipose tissue was independently associated with a 24% increase in the risk of developing cardiovascular disease during follow-up. Dividing the study population into quartiles on the basis of their extent of visceral adipose tissue, the cumulative incidence of cardiovascular disease rose in stepwise fashion, with subjects in the lowest quartile having the least cardiovascular events and those in the top quartile having the most.
Having more lower body subcutaneous fat had the opposite effect. For every 1–standard deviation increase in the amount of fat at that location, the cardiovascular event risk dropped by 27%.
Participants’ amount of abdominal subcutaneous fat didn’t affect their cardiovascular event risk one way or another. Nor did BMI, waist circumference, waist-hip ratio, or the amount of liver fat on MRI show any significant association with cardiovascular disease risk.
"These results really underscore the biologic importance of body fat distribution with regard to cardiovascular disease risk in obesity and suggest a possible prognostic role for imaging-based assessment of body fat distribution in high-risk obese patients," according to Dr. Neeland.
One intriguing clinical implication of this study is that preventing accumulation of visceral adipose tissue may have benefit in terms of cardiovascular disease prevention even in the absence of meaningful weight loss. It’s possible that new drugs could be developed that lower cardiovascular risk in obese patients by changing their body fat distribution profile rather than lopping off pounds.
In the Dallas study, increased visceral abdominal tissue was consistently associated with a higher risk of cardiovascular disease across subgroups based upon age, race, sex, and BMI.
"Interestingly, those with increased visceral abdominal fat who were less than 40 years of age had greater risk for cardiovascular disease than [did] those over 40. This could suggest that visceral abdominal tissue has a greater impact on the young, in whom other cardiovascular risk factors have not yet accumulated over time," Dr. Neeland observed.
The cardiovascular event endpoint in the study was a composite of cardiovascular death, acute MI, stroke, heart failure, atrial fibrillation, or event-driven coronary or peripheral artery revascularization.
The Dallas Heart Study is funded by the Donald W. Reynolds Foundation. Dr. Neeland reported having no financial conflicts.
DALLAS – It’s not obesity per se that affects cardiovascular risk, it’s where that excess body fat is stored, according to the results of a novel adipose tissue–imaging study.
Excess visceral adipose tissue is independently associated with increased risk of developing cardiovascular disease. In contrast, increased lower body subcutaneous adipose tissue – that is, fat around the hips and a big butt – actually seems to protect against cardiovascular disease, Dr. Ian J. Neeland reported at the American Heart Association scientific sessions.
He presented an analysis of 972 obese participants in the Dallas Heart Study with a mean age of 44 years at enrollment and no baseline cardiovascular disease. All underwent dual-energy x-ray absorptiometry and MRI assessment of their body fat distribution, focusing on the visceral, abdominal subcutaneous, and lower body subcutaneous adipose tissue depots. Participants were then followed prospectively for a median 8.1 years, during which 91 cardiovascular events occurred in 68 subjects.
The impetus for the adipose tissue imaging study was the researchers’ recognition that obesity is a heterogeneous disorder.
"Currently, we know that obesity is associated with incident cardiovascular disease at a general population level. However, body mass index alone is really an inadequate marker of risk among the obese. Many individuals with even high BMIs do not develop cardiovascular disease. Marked abdominal obesity is a stronger predictor of cardiovascular disease but still lacks the necessary specificity. So there’s really a clinical need for tools to differentiate obese individuals who will develop cardiovascular disease from those who will be free of cardiovascular disease for their lifetime," explained Dr. Neeland, a fellow in cardiovascular medicine at the University of Texas Southwestern Medical Center, Dallas.
In a multivariate analysis adjusted for age, sex, race, and the conventional cardiovascular risk factors, each 1–standard deviation increase in visceral adipose tissue was independently associated with a 24% increase in the risk of developing cardiovascular disease during follow-up. Dividing the study population into quartiles on the basis of their extent of visceral adipose tissue, the cumulative incidence of cardiovascular disease rose in stepwise fashion, with subjects in the lowest quartile having the least cardiovascular events and those in the top quartile having the most.
Having more lower body subcutaneous fat had the opposite effect. For every 1–standard deviation increase in the amount of fat at that location, the cardiovascular event risk dropped by 27%.
Participants’ amount of abdominal subcutaneous fat didn’t affect their cardiovascular event risk one way or another. Nor did BMI, waist circumference, waist-hip ratio, or the amount of liver fat on MRI show any significant association with cardiovascular disease risk.
"These results really underscore the biologic importance of body fat distribution with regard to cardiovascular disease risk in obesity and suggest a possible prognostic role for imaging-based assessment of body fat distribution in high-risk obese patients," according to Dr. Neeland.
One intriguing clinical implication of this study is that preventing accumulation of visceral adipose tissue may have benefit in terms of cardiovascular disease prevention even in the absence of meaningful weight loss. It’s possible that new drugs could be developed that lower cardiovascular risk in obese patients by changing their body fat distribution profile rather than lopping off pounds.
In the Dallas study, increased visceral abdominal tissue was consistently associated with a higher risk of cardiovascular disease across subgroups based upon age, race, sex, and BMI.
"Interestingly, those with increased visceral abdominal fat who were less than 40 years of age had greater risk for cardiovascular disease than [did] those over 40. This could suggest that visceral abdominal tissue has a greater impact on the young, in whom other cardiovascular risk factors have not yet accumulated over time," Dr. Neeland observed.
The cardiovascular event endpoint in the study was a composite of cardiovascular death, acute MI, stroke, heart failure, atrial fibrillation, or event-driven coronary or peripheral artery revascularization.
The Dallas Heart Study is funded by the Donald W. Reynolds Foundation. Dr. Neeland reported having no financial conflicts.
DALLAS – It’s not obesity per se that affects cardiovascular risk, it’s where that excess body fat is stored, according to the results of a novel adipose tissue–imaging study.
Excess visceral adipose tissue is independently associated with increased risk of developing cardiovascular disease. In contrast, increased lower body subcutaneous adipose tissue – that is, fat around the hips and a big butt – actually seems to protect against cardiovascular disease, Dr. Ian J. Neeland reported at the American Heart Association scientific sessions.
He presented an analysis of 972 obese participants in the Dallas Heart Study with a mean age of 44 years at enrollment and no baseline cardiovascular disease. All underwent dual-energy x-ray absorptiometry and MRI assessment of their body fat distribution, focusing on the visceral, abdominal subcutaneous, and lower body subcutaneous adipose tissue depots. Participants were then followed prospectively for a median 8.1 years, during which 91 cardiovascular events occurred in 68 subjects.
The impetus for the adipose tissue imaging study was the researchers’ recognition that obesity is a heterogeneous disorder.
"Currently, we know that obesity is associated with incident cardiovascular disease at a general population level. However, body mass index alone is really an inadequate marker of risk among the obese. Many individuals with even high BMIs do not develop cardiovascular disease. Marked abdominal obesity is a stronger predictor of cardiovascular disease but still lacks the necessary specificity. So there’s really a clinical need for tools to differentiate obese individuals who will develop cardiovascular disease from those who will be free of cardiovascular disease for their lifetime," explained Dr. Neeland, a fellow in cardiovascular medicine at the University of Texas Southwestern Medical Center, Dallas.
In a multivariate analysis adjusted for age, sex, race, and the conventional cardiovascular risk factors, each 1–standard deviation increase in visceral adipose tissue was independently associated with a 24% increase in the risk of developing cardiovascular disease during follow-up. Dividing the study population into quartiles on the basis of their extent of visceral adipose tissue, the cumulative incidence of cardiovascular disease rose in stepwise fashion, with subjects in the lowest quartile having the least cardiovascular events and those in the top quartile having the most.
Having more lower body subcutaneous fat had the opposite effect. For every 1–standard deviation increase in the amount of fat at that location, the cardiovascular event risk dropped by 27%.
Participants’ amount of abdominal subcutaneous fat didn’t affect their cardiovascular event risk one way or another. Nor did BMI, waist circumference, waist-hip ratio, or the amount of liver fat on MRI show any significant association with cardiovascular disease risk.
"These results really underscore the biologic importance of body fat distribution with regard to cardiovascular disease risk in obesity and suggest a possible prognostic role for imaging-based assessment of body fat distribution in high-risk obese patients," according to Dr. Neeland.
One intriguing clinical implication of this study is that preventing accumulation of visceral adipose tissue may have benefit in terms of cardiovascular disease prevention even in the absence of meaningful weight loss. It’s possible that new drugs could be developed that lower cardiovascular risk in obese patients by changing their body fat distribution profile rather than lopping off pounds.
In the Dallas study, increased visceral abdominal tissue was consistently associated with a higher risk of cardiovascular disease across subgroups based upon age, race, sex, and BMI.
"Interestingly, those with increased visceral abdominal fat who were less than 40 years of age had greater risk for cardiovascular disease than [did] those over 40. This could suggest that visceral abdominal tissue has a greater impact on the young, in whom other cardiovascular risk factors have not yet accumulated over time," Dr. Neeland observed.
The cardiovascular event endpoint in the study was a composite of cardiovascular death, acute MI, stroke, heart failure, atrial fibrillation, or event-driven coronary or peripheral artery revascularization.
The Dallas Heart Study is funded by the Donald W. Reynolds Foundation. Dr. Neeland reported having no financial conflicts.
AT THE AHA SCIENTIFIC SESSIONS
PCSK9 antibody shows safety, efficacy to 1 year
DALLAS – Monthly treatment with a human antibody directed against the PCSK9 enzyme was safe and effective for substantially lowering low-density-lipoprotein cholesterol levels in 736 patients treated for 1 year in a controlled phase II study, the longest and largest series of patients treated with a PCSK9 antibody yet reported.
An injection of evolocumab (formerly known as Amgen 145) a human antibody to the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme once every 4 weeks led to an average 52% reduction in blood levels of LDL cholesterol after 1 year on top of background treatment with standard-of-care medications, which in many cases also included maximal statin treatment, Dr. Michael J. Koren said at the American Heart Association scientific sessions.
In addition, the safety results for evolocumab "were very clean," he said, with no evidence that patients developed neutralizing antibody against the monoclonal antibody drug, and with injection-site reactions occurring in 5% of treated patients with one patient withdrawing because of the injection-site effect.
The Food and Drug Administration should "certainly vote to approve these drugs for familial hypercholesterolemia," said Dr. Koren, director of noninvasive cardiology at Jacksonville (Fla.) Memorial Hospital. "These are patients in whom we see a lot of complication, and we need lots of ways to lower their cholesterol."
PCSK9-inhibitor treatment of other patient populations, such as patients who are statin intolerant, will "probably need outcome studies for us to feel comfortable with widespread adoption," he added. Dr. Eckel estimated that about 4 million American patients who have been prescribed a statin can’t take the drug because of intolerance.
The Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) enrolled patients who had been enrolled in any of four prior phase II studies of evolocumab that each ran for 12 weeks. OSLER randomized 736 patients at 155 centers in 17 countries to receive 420 mg of evolocumab as a subcutaneous injection every 4 weeks in addition to standard-of-care treatment; 368 patients were assigned to standard of care only as controls. Patients averaged 56 years of age, their average LDL cholesterol level at baseline was about 140 mg/dL, and just under two-thirds of patients also received treatment with a statin.
After 1 year, 86% of the evolocumab-treated patients had an LDL cholesterol level below 100 mg/dL and 63% had their level below 70 mg/dL. In contrast, 16% and 1% respectively of patients on standard care reached these levels.
"We’re super pleased with the safety and tolerability data we’ve seen so far," Dr. Koren said. Even among the 98 patients treated with evolocumab who had their LDL cholesterol level below 25 mg/dL at 1year, the data showed no signal of increased serious adverse reactions or kidney or liver abnormalities. The only suggestion of a possible problem was a reported 9% incidence of headaches, compared with a 3% rate among patients on standard care and a 6% rate among patients on evolocumab for 1 year with LDL cholesterol levels of less than 50 mg/dL.
Concurrent with Dr. Koren’s report, the results also were published online (Circulation 2013;128 [doi:10.1161/CIRCULATIONAHA.113.007012]).
OSLER was sponsored by Amgen. Dr. Koren said that he has received research support from Amgen and from Regeneron, Sanofi, Roche, and Pfizer.
On Twitter @mitchelzoler
The OSLER results represent some progress for the PCSK9 antibodies. The results come from the longest PCSK9-antibody study so far reported. The adverse effects were not very noteworthy, and the 50% reduction in LDL cholesterol was sustained over 1 year. The adverse effects seen in patients whose LDL cholesterol level fell below 25 mg/dL did not look alarming. The results also showed an intriguing reduction in lipoprotein(a) of about 20% beyond what was achieved by standard care.
These results still leave many questions, such as the safety and efficacy of longer-term treatment. Having 1-year treatment results is nice, but it’s not like having 5-year or 20-year results. Another important issue is which patients are potential candidates for such treatment. Some people have estimated that as many as 4 million U.S. patients who need cholesterol-lowering treatment are statin intolerant, defined as patients who developed myopathy from monotherapy with two or more different statins. We also anxiously await the results from ongoing trials that are assessing the impact of PCSK9-antibody treatment on cardiovascular disease outcomes.
A trickier issue is whether a new agent can benefit patients on standard LDL-reducing regimens who have not reached their "goal" level. Now that the new cholesterol guidelines (Circulation 2013;128 [doi:10.1161/01.cir.0000437738.63853.7a]) eliminate target LDL levels for treatment, do patients still have goals? I believe the answer is yes.
Even though the guidelines concluded that no evidence exists for setting LDL-cholesterol goals, this does not means that goal-setting must be eliminated. Physicians practice medicine in the clinic, and setting a target goal for a patient’s LDL cholesterol level is a useful approach for treating patients with lipid disorders. Target goals may not be evidence based, but they can be part of effective practice.
Dr. Robert H. Eckel is professor of medicine at the University of Colorado, Aurora. He said that he had no disclosures. He made these comments as designated discussant for the report.
The OSLER results represent some progress for the PCSK9 antibodies. The results come from the longest PCSK9-antibody study so far reported. The adverse effects were not very noteworthy, and the 50% reduction in LDL cholesterol was sustained over 1 year. The adverse effects seen in patients whose LDL cholesterol level fell below 25 mg/dL did not look alarming. The results also showed an intriguing reduction in lipoprotein(a) of about 20% beyond what was achieved by standard care.
These results still leave many questions, such as the safety and efficacy of longer-term treatment. Having 1-year treatment results is nice, but it’s not like having 5-year or 20-year results. Another important issue is which patients are potential candidates for such treatment. Some people have estimated that as many as 4 million U.S. patients who need cholesterol-lowering treatment are statin intolerant, defined as patients who developed myopathy from monotherapy with two or more different statins. We also anxiously await the results from ongoing trials that are assessing the impact of PCSK9-antibody treatment on cardiovascular disease outcomes.
A trickier issue is whether a new agent can benefit patients on standard LDL-reducing regimens who have not reached their "goal" level. Now that the new cholesterol guidelines (Circulation 2013;128 [doi:10.1161/01.cir.0000437738.63853.7a]) eliminate target LDL levels for treatment, do patients still have goals? I believe the answer is yes.
Even though the guidelines concluded that no evidence exists for setting LDL-cholesterol goals, this does not means that goal-setting must be eliminated. Physicians practice medicine in the clinic, and setting a target goal for a patient’s LDL cholesterol level is a useful approach for treating patients with lipid disorders. Target goals may not be evidence based, but they can be part of effective practice.
Dr. Robert H. Eckel is professor of medicine at the University of Colorado, Aurora. He said that he had no disclosures. He made these comments as designated discussant for the report.
The OSLER results represent some progress for the PCSK9 antibodies. The results come from the longest PCSK9-antibody study so far reported. The adverse effects were not very noteworthy, and the 50% reduction in LDL cholesterol was sustained over 1 year. The adverse effects seen in patients whose LDL cholesterol level fell below 25 mg/dL did not look alarming. The results also showed an intriguing reduction in lipoprotein(a) of about 20% beyond what was achieved by standard care.
These results still leave many questions, such as the safety and efficacy of longer-term treatment. Having 1-year treatment results is nice, but it’s not like having 5-year or 20-year results. Another important issue is which patients are potential candidates for such treatment. Some people have estimated that as many as 4 million U.S. patients who need cholesterol-lowering treatment are statin intolerant, defined as patients who developed myopathy from monotherapy with two or more different statins. We also anxiously await the results from ongoing trials that are assessing the impact of PCSK9-antibody treatment on cardiovascular disease outcomes.
A trickier issue is whether a new agent can benefit patients on standard LDL-reducing regimens who have not reached their "goal" level. Now that the new cholesterol guidelines (Circulation 2013;128 [doi:10.1161/01.cir.0000437738.63853.7a]) eliminate target LDL levels for treatment, do patients still have goals? I believe the answer is yes.
Even though the guidelines concluded that no evidence exists for setting LDL-cholesterol goals, this does not means that goal-setting must be eliminated. Physicians practice medicine in the clinic, and setting a target goal for a patient’s LDL cholesterol level is a useful approach for treating patients with lipid disorders. Target goals may not be evidence based, but they can be part of effective practice.
Dr. Robert H. Eckel is professor of medicine at the University of Colorado, Aurora. He said that he had no disclosures. He made these comments as designated discussant for the report.
DALLAS – Monthly treatment with a human antibody directed against the PCSK9 enzyme was safe and effective for substantially lowering low-density-lipoprotein cholesterol levels in 736 patients treated for 1 year in a controlled phase II study, the longest and largest series of patients treated with a PCSK9 antibody yet reported.
An injection of evolocumab (formerly known as Amgen 145) a human antibody to the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme once every 4 weeks led to an average 52% reduction in blood levels of LDL cholesterol after 1 year on top of background treatment with standard-of-care medications, which in many cases also included maximal statin treatment, Dr. Michael J. Koren said at the American Heart Association scientific sessions.
In addition, the safety results for evolocumab "were very clean," he said, with no evidence that patients developed neutralizing antibody against the monoclonal antibody drug, and with injection-site reactions occurring in 5% of treated patients with one patient withdrawing because of the injection-site effect.
The Food and Drug Administration should "certainly vote to approve these drugs for familial hypercholesterolemia," said Dr. Koren, director of noninvasive cardiology at Jacksonville (Fla.) Memorial Hospital. "These are patients in whom we see a lot of complication, and we need lots of ways to lower their cholesterol."
PCSK9-inhibitor treatment of other patient populations, such as patients who are statin intolerant, will "probably need outcome studies for us to feel comfortable with widespread adoption," he added. Dr. Eckel estimated that about 4 million American patients who have been prescribed a statin can’t take the drug because of intolerance.
The Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) enrolled patients who had been enrolled in any of four prior phase II studies of evolocumab that each ran for 12 weeks. OSLER randomized 736 patients at 155 centers in 17 countries to receive 420 mg of evolocumab as a subcutaneous injection every 4 weeks in addition to standard-of-care treatment; 368 patients were assigned to standard of care only as controls. Patients averaged 56 years of age, their average LDL cholesterol level at baseline was about 140 mg/dL, and just under two-thirds of patients also received treatment with a statin.
After 1 year, 86% of the evolocumab-treated patients had an LDL cholesterol level below 100 mg/dL and 63% had their level below 70 mg/dL. In contrast, 16% and 1% respectively of patients on standard care reached these levels.
"We’re super pleased with the safety and tolerability data we’ve seen so far," Dr. Koren said. Even among the 98 patients treated with evolocumab who had their LDL cholesterol level below 25 mg/dL at 1year, the data showed no signal of increased serious adverse reactions or kidney or liver abnormalities. The only suggestion of a possible problem was a reported 9% incidence of headaches, compared with a 3% rate among patients on standard care and a 6% rate among patients on evolocumab for 1 year with LDL cholesterol levels of less than 50 mg/dL.
Concurrent with Dr. Koren’s report, the results also were published online (Circulation 2013;128 [doi:10.1161/CIRCULATIONAHA.113.007012]).
OSLER was sponsored by Amgen. Dr. Koren said that he has received research support from Amgen and from Regeneron, Sanofi, Roche, and Pfizer.
On Twitter @mitchelzoler
DALLAS – Monthly treatment with a human antibody directed against the PCSK9 enzyme was safe and effective for substantially lowering low-density-lipoprotein cholesterol levels in 736 patients treated for 1 year in a controlled phase II study, the longest and largest series of patients treated with a PCSK9 antibody yet reported.
An injection of evolocumab (formerly known as Amgen 145) a human antibody to the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme once every 4 weeks led to an average 52% reduction in blood levels of LDL cholesterol after 1 year on top of background treatment with standard-of-care medications, which in many cases also included maximal statin treatment, Dr. Michael J. Koren said at the American Heart Association scientific sessions.
In addition, the safety results for evolocumab "were very clean," he said, with no evidence that patients developed neutralizing antibody against the monoclonal antibody drug, and with injection-site reactions occurring in 5% of treated patients with one patient withdrawing because of the injection-site effect.
The Food and Drug Administration should "certainly vote to approve these drugs for familial hypercholesterolemia," said Dr. Koren, director of noninvasive cardiology at Jacksonville (Fla.) Memorial Hospital. "These are patients in whom we see a lot of complication, and we need lots of ways to lower their cholesterol."
PCSK9-inhibitor treatment of other patient populations, such as patients who are statin intolerant, will "probably need outcome studies for us to feel comfortable with widespread adoption," he added. Dr. Eckel estimated that about 4 million American patients who have been prescribed a statin can’t take the drug because of intolerance.
The Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) enrolled patients who had been enrolled in any of four prior phase II studies of evolocumab that each ran for 12 weeks. OSLER randomized 736 patients at 155 centers in 17 countries to receive 420 mg of evolocumab as a subcutaneous injection every 4 weeks in addition to standard-of-care treatment; 368 patients were assigned to standard of care only as controls. Patients averaged 56 years of age, their average LDL cholesterol level at baseline was about 140 mg/dL, and just under two-thirds of patients also received treatment with a statin.
After 1 year, 86% of the evolocumab-treated patients had an LDL cholesterol level below 100 mg/dL and 63% had their level below 70 mg/dL. In contrast, 16% and 1% respectively of patients on standard care reached these levels.
"We’re super pleased with the safety and tolerability data we’ve seen so far," Dr. Koren said. Even among the 98 patients treated with evolocumab who had their LDL cholesterol level below 25 mg/dL at 1year, the data showed no signal of increased serious adverse reactions or kidney or liver abnormalities. The only suggestion of a possible problem was a reported 9% incidence of headaches, compared with a 3% rate among patients on standard care and a 6% rate among patients on evolocumab for 1 year with LDL cholesterol levels of less than 50 mg/dL.
Concurrent with Dr. Koren’s report, the results also were published online (Circulation 2013;128 [doi:10.1161/CIRCULATIONAHA.113.007012]).
OSLER was sponsored by Amgen. Dr. Koren said that he has received research support from Amgen and from Regeneron, Sanofi, Roche, and Pfizer.
On Twitter @mitchelzoler
AT THE AHA SCIENTIFIC SESSIONS
Major finding: Treatment with evolocumab every 4 weeks for 1 year safely cut average LDL cholesterol levels by 50%, compared with controls.
Data source: OSLER, an open-label study that randomized 368 patients to standard care and 736 to standard care plus evolocumab treatment.
Disclosures: OSLER was sponsored by Amgen. Dr. Koren said that he has received research support from Amgen and from Regeneron, Sanofi, Roche, and Pfizer.
CRT shown highly cost effective in mild heart failure
DALLAS – Cardiac resynchronization therapy demonstrated a robust cost-effectiveness of $18,275 per quality-adjusted life-year gained in an analysis from the landmark REVERSE trial.
REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) was the first large, international, randomized, double-blind clinical trial to establish that cardiac resynchronization therapy (CRT) is clinically beneficial in patients with mild heart failure (J. Am. Coll. Cardiol. 2008;52:1834-43). The incremental cost-effectiveness ratio (ICER) of $18,275 per quality-adjusted life-year (QALY) gained in the new secondary analysis is well under the figure of $50,000 per QALY gained generally accepted as the benchmark defining cost-effectiveness, Dr. Michael R. Gold noted at the American Heart Association scientific sessions.
He presented an analysis based on an economic model that utilized 5-year follow-up data from REVERSE to predict the impact of CRT on life-years and costs out to 10 years. REVERSE included 610 patients with New York Heart Association (NYHA) class I or II heart failure, a QRS interval of 120 milliseconds or more, and a left ventricular ejection fraction of 40% or less, all of whom were on optimal medical therapy. Participants were implanted with a CRT device, which was placed in either the on or off position for the first year in North American patients or the first 2 years in Europeans, after which everyone’s device was switched on for the remainder of follow-up.
The model projected that patients with CRT turned on would gain an extra 0.83 years of life compared with those without active CRT. The ICER ratio of $18,275 per QALY gained through CRT was determined by applying costs based on national Medicare rates to the reduced heart failure hospitalization rate resulting from the device therapy, explained Dr. Gold, professor of medicine and director of cardiology at the Medical University of South Carolina, Charleston.
CRT was found to be highly cost effective in all patient subgroups examined in the analysis. For example, the projected ICER with cardiac resynchronization therapy switched on in patients with heart failure of ischemic etiology was $15,648 per QALY. In those with left bundle branch block, it was $22,086 per QALY.
Significantly fewer patients were projected to progress to NYHA class III heart failure over the course of 10 years with CRT on than off, by a margin of 18.7% to 28.1%. From the 5-year follow-up data, it was estimated that at 10 years 31% of the CRT-on group would be in NYHA class I, compared with 22.3% of controls with CRT off.
A combined CRT/implantable cardioverter-defibrillator (CRT-D) with both functions switched on had an ICER of $13,050 per QALY gained compared with CRT only.
On the basis of the results of REVERSE and the Resynchronization/Defibrillation in Ambulatory Heart Failure Trial (RAFT, N. Engl. J. Med. 2010;363:2385-95), in 2012 the Food and Drug Administration expanded the indication for Medtronic’s CRT-D device to include the treatment of patients with NYHA class II heart failure with a left ventricular ejection fraction of 30% or less, left bundle branch block, and a QRS duration of at least 130 milliseconds. The new secondary analysis of REVERSE demonstrates that CRT is not only clinically effective in patients with mild heart failure, as recognized by the FDA, it is highly cost effective as well, according to Dr. Gold.
The REVERSE trial was sponsored by Medtronic. Dr. Gold is a consultant to Medtronic and Boston Scientific.
DALLAS – Cardiac resynchronization therapy demonstrated a robust cost-effectiveness of $18,275 per quality-adjusted life-year gained in an analysis from the landmark REVERSE trial.
REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) was the first large, international, randomized, double-blind clinical trial to establish that cardiac resynchronization therapy (CRT) is clinically beneficial in patients with mild heart failure (J. Am. Coll. Cardiol. 2008;52:1834-43). The incremental cost-effectiveness ratio (ICER) of $18,275 per quality-adjusted life-year (QALY) gained in the new secondary analysis is well under the figure of $50,000 per QALY gained generally accepted as the benchmark defining cost-effectiveness, Dr. Michael R. Gold noted at the American Heart Association scientific sessions.
He presented an analysis based on an economic model that utilized 5-year follow-up data from REVERSE to predict the impact of CRT on life-years and costs out to 10 years. REVERSE included 610 patients with New York Heart Association (NYHA) class I or II heart failure, a QRS interval of 120 milliseconds or more, and a left ventricular ejection fraction of 40% or less, all of whom were on optimal medical therapy. Participants were implanted with a CRT device, which was placed in either the on or off position for the first year in North American patients or the first 2 years in Europeans, after which everyone’s device was switched on for the remainder of follow-up.
The model projected that patients with CRT turned on would gain an extra 0.83 years of life compared with those without active CRT. The ICER ratio of $18,275 per QALY gained through CRT was determined by applying costs based on national Medicare rates to the reduced heart failure hospitalization rate resulting from the device therapy, explained Dr. Gold, professor of medicine and director of cardiology at the Medical University of South Carolina, Charleston.
CRT was found to be highly cost effective in all patient subgroups examined in the analysis. For example, the projected ICER with cardiac resynchronization therapy switched on in patients with heart failure of ischemic etiology was $15,648 per QALY. In those with left bundle branch block, it was $22,086 per QALY.
Significantly fewer patients were projected to progress to NYHA class III heart failure over the course of 10 years with CRT on than off, by a margin of 18.7% to 28.1%. From the 5-year follow-up data, it was estimated that at 10 years 31% of the CRT-on group would be in NYHA class I, compared with 22.3% of controls with CRT off.
A combined CRT/implantable cardioverter-defibrillator (CRT-D) with both functions switched on had an ICER of $13,050 per QALY gained compared with CRT only.
On the basis of the results of REVERSE and the Resynchronization/Defibrillation in Ambulatory Heart Failure Trial (RAFT, N. Engl. J. Med. 2010;363:2385-95), in 2012 the Food and Drug Administration expanded the indication for Medtronic’s CRT-D device to include the treatment of patients with NYHA class II heart failure with a left ventricular ejection fraction of 30% or less, left bundle branch block, and a QRS duration of at least 130 milliseconds. The new secondary analysis of REVERSE demonstrates that CRT is not only clinically effective in patients with mild heart failure, as recognized by the FDA, it is highly cost effective as well, according to Dr. Gold.
The REVERSE trial was sponsored by Medtronic. Dr. Gold is a consultant to Medtronic and Boston Scientific.
DALLAS – Cardiac resynchronization therapy demonstrated a robust cost-effectiveness of $18,275 per quality-adjusted life-year gained in an analysis from the landmark REVERSE trial.
REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) was the first large, international, randomized, double-blind clinical trial to establish that cardiac resynchronization therapy (CRT) is clinically beneficial in patients with mild heart failure (J. Am. Coll. Cardiol. 2008;52:1834-43). The incremental cost-effectiveness ratio (ICER) of $18,275 per quality-adjusted life-year (QALY) gained in the new secondary analysis is well under the figure of $50,000 per QALY gained generally accepted as the benchmark defining cost-effectiveness, Dr. Michael R. Gold noted at the American Heart Association scientific sessions.
He presented an analysis based on an economic model that utilized 5-year follow-up data from REVERSE to predict the impact of CRT on life-years and costs out to 10 years. REVERSE included 610 patients with New York Heart Association (NYHA) class I or II heart failure, a QRS interval of 120 milliseconds or more, and a left ventricular ejection fraction of 40% or less, all of whom were on optimal medical therapy. Participants were implanted with a CRT device, which was placed in either the on or off position for the first year in North American patients or the first 2 years in Europeans, after which everyone’s device was switched on for the remainder of follow-up.
The model projected that patients with CRT turned on would gain an extra 0.83 years of life compared with those without active CRT. The ICER ratio of $18,275 per QALY gained through CRT was determined by applying costs based on national Medicare rates to the reduced heart failure hospitalization rate resulting from the device therapy, explained Dr. Gold, professor of medicine and director of cardiology at the Medical University of South Carolina, Charleston.
CRT was found to be highly cost effective in all patient subgroups examined in the analysis. For example, the projected ICER with cardiac resynchronization therapy switched on in patients with heart failure of ischemic etiology was $15,648 per QALY. In those with left bundle branch block, it was $22,086 per QALY.
Significantly fewer patients were projected to progress to NYHA class III heart failure over the course of 10 years with CRT on than off, by a margin of 18.7% to 28.1%. From the 5-year follow-up data, it was estimated that at 10 years 31% of the CRT-on group would be in NYHA class I, compared with 22.3% of controls with CRT off.
A combined CRT/implantable cardioverter-defibrillator (CRT-D) with both functions switched on had an ICER of $13,050 per QALY gained compared with CRT only.
On the basis of the results of REVERSE and the Resynchronization/Defibrillation in Ambulatory Heart Failure Trial (RAFT, N. Engl. J. Med. 2010;363:2385-95), in 2012 the Food and Drug Administration expanded the indication for Medtronic’s CRT-D device to include the treatment of patients with NYHA class II heart failure with a left ventricular ejection fraction of 30% or less, left bundle branch block, and a QRS duration of at least 130 milliseconds. The new secondary analysis of REVERSE demonstrates that CRT is not only clinically effective in patients with mild heart failure, as recognized by the FDA, it is highly cost effective as well, according to Dr. Gold.
The REVERSE trial was sponsored by Medtronic. Dr. Gold is a consultant to Medtronic and Boston Scientific.
AT THE AHA SCIENTIFIC SESSIONS
Major finding: Implantation of a cardiac resynchronization therapy device in patients with mild heart failure on optimal medical therapy had a projected cost-effectiveness of $18,275 per quality-adjusted life-year gained, compared with controls on optimal medical therapy alone.
Data source: This cost-benefit analysis utilized 5-year follow-up data from the randomized, double-blind prospective REVERSE trial, in which 610 patients with mild heart failure were implanted with a cardiac resynchronization therapy device placed in the on or off position.
Disclosures: The study was sponsored by Medtronic. The presenter is a consultant to Medtronic and Boston Scientific.
Postop atrial fib has two peaks
DALLAS – New-onset postoperative atrial fibrillation following cardiac surgery occurs in two distinct phases, with different risk factors for each.
That’s the key finding in an analysis of the recent experience at the University of Alabama, Birmingham, where new-onset postoperative AF occurred in 27% of 1,583 consecutive patients who underwent coronary artery bypass graft and/or valve surgery.
The first peak in the onset of postoperative AF occurred in the first 3 hours after surgery. This was followed by a sharp decline in incidence over the next 24 hours. The second peak happened at postoperative day 2, followed by a more gradual tail off, Dr. Spencer J. Melby reported at the American Heart Association scientific sessions.
Ninety-six percent of all cases of postoperative AF in this retrospective chart review began within the first 7 days after surgery. Of the 423 patients who developed this common and vexing condition, 16% did so within the first 24 hours, 48% had their onset at 24-72 hours, and 36% did so after 72 hours, according to Dr. Melby, a cardiothoracic surgeon at the university.
In a multivariate analysis, the most potent risk factor for onset of postoperative AF during the first phase was mitral valve repair or replacement, which was associated with a 2.5-fold increased risk. The other significant risk factors for early-onset AF were older age – with 70-year-olds having a 1.6-fold greater risk than 50-year-olds – and longer ischemic time, with patients whose cross-clamp time was 70 minutes having a 1.3-fold greater risk compared with those who had a cross-clamp time of 35 minutes.
Advanced age was also a risk factor for late-phase onset of AF, but it was a stronger risk factor there than for early onset AF, with 70-year-olds being at threefold greater risk than 50-year-olds – nearly twice as great a risk as for early-onset postoperative AF. The other significant risk factors for late-phase postoperative AF in a multivariate analysis were white race, with a 1.9-fold increased risk, and heavier body weight, with patients weighing 100 kg being at 1.6-fold greater risk than those tipping the scales at 70 kg.
"We believe that these different risk factors at each time phase are indicative of change over time in the mechanisms that drive postoperative atrial fibrillation," the surgeon said.
The first peak may be the result of tissue trauma, which is typically greater with more complex operations having longer cross-clamp times. And mitral valve procedures often entail contact with the left atrium.
"We’ve found that in patients with onset in the second peak there’s a polymorphonuclear leukocyte riot going on in the pericardial space after surgery. Inflammation is high, oxidative stress is high. Troponin levels are extremely high in the pericardial fluid, so there are problems in the heart muscle itself. The body is trying to heal and may be overdoing it as reflected by the inflammation in that space," Dr. Melby explained.
Dr. Brendan M. Everett, session cochair, noted that postoperative day 2 is when a host of process-of-care issues potentially relevant to postoperative AF come into play.
"Postop day 2 is when pain control begins to slip a bit. Patients are mobilized, chest tubes are pulled. A lot of factors are going on that are very important overall to getting a patient up and out of the hospital but are serious stimuli – adrenergic and otherwise – that may force a patient to go into atrial fibrillation," observed Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.
Audience members praised Dr. Melby’s study as having "tremendous implications" for clinical practice, especially with regard to patient management guidelines. Dr. Melby noted that postoperative AF is a costly matter: It increases hospital length of stay by 1-2 days at a cost of roughly $10,000 per episode. Nationally, postoperative AF costs $4 billion per year.
Dr. Melby reported having no financial conflicts regarding his study.
DALLAS – New-onset postoperative atrial fibrillation following cardiac surgery occurs in two distinct phases, with different risk factors for each.
That’s the key finding in an analysis of the recent experience at the University of Alabama, Birmingham, where new-onset postoperative AF occurred in 27% of 1,583 consecutive patients who underwent coronary artery bypass graft and/or valve surgery.
The first peak in the onset of postoperative AF occurred in the first 3 hours after surgery. This was followed by a sharp decline in incidence over the next 24 hours. The second peak happened at postoperative day 2, followed by a more gradual tail off, Dr. Spencer J. Melby reported at the American Heart Association scientific sessions.
Ninety-six percent of all cases of postoperative AF in this retrospective chart review began within the first 7 days after surgery. Of the 423 patients who developed this common and vexing condition, 16% did so within the first 24 hours, 48% had their onset at 24-72 hours, and 36% did so after 72 hours, according to Dr. Melby, a cardiothoracic surgeon at the university.
In a multivariate analysis, the most potent risk factor for onset of postoperative AF during the first phase was mitral valve repair or replacement, which was associated with a 2.5-fold increased risk. The other significant risk factors for early-onset AF were older age – with 70-year-olds having a 1.6-fold greater risk than 50-year-olds – and longer ischemic time, with patients whose cross-clamp time was 70 minutes having a 1.3-fold greater risk compared with those who had a cross-clamp time of 35 minutes.
Advanced age was also a risk factor for late-phase onset of AF, but it was a stronger risk factor there than for early onset AF, with 70-year-olds being at threefold greater risk than 50-year-olds – nearly twice as great a risk as for early-onset postoperative AF. The other significant risk factors for late-phase postoperative AF in a multivariate analysis were white race, with a 1.9-fold increased risk, and heavier body weight, with patients weighing 100 kg being at 1.6-fold greater risk than those tipping the scales at 70 kg.
"We believe that these different risk factors at each time phase are indicative of change over time in the mechanisms that drive postoperative atrial fibrillation," the surgeon said.
The first peak may be the result of tissue trauma, which is typically greater with more complex operations having longer cross-clamp times. And mitral valve procedures often entail contact with the left atrium.
"We’ve found that in patients with onset in the second peak there’s a polymorphonuclear leukocyte riot going on in the pericardial space after surgery. Inflammation is high, oxidative stress is high. Troponin levels are extremely high in the pericardial fluid, so there are problems in the heart muscle itself. The body is trying to heal and may be overdoing it as reflected by the inflammation in that space," Dr. Melby explained.
Dr. Brendan M. Everett, session cochair, noted that postoperative day 2 is when a host of process-of-care issues potentially relevant to postoperative AF come into play.
"Postop day 2 is when pain control begins to slip a bit. Patients are mobilized, chest tubes are pulled. A lot of factors are going on that are very important overall to getting a patient up and out of the hospital but are serious stimuli – adrenergic and otherwise – that may force a patient to go into atrial fibrillation," observed Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.
Audience members praised Dr. Melby’s study as having "tremendous implications" for clinical practice, especially with regard to patient management guidelines. Dr. Melby noted that postoperative AF is a costly matter: It increases hospital length of stay by 1-2 days at a cost of roughly $10,000 per episode. Nationally, postoperative AF costs $4 billion per year.
Dr. Melby reported having no financial conflicts regarding his study.
DALLAS – New-onset postoperative atrial fibrillation following cardiac surgery occurs in two distinct phases, with different risk factors for each.
That’s the key finding in an analysis of the recent experience at the University of Alabama, Birmingham, where new-onset postoperative AF occurred in 27% of 1,583 consecutive patients who underwent coronary artery bypass graft and/or valve surgery.
The first peak in the onset of postoperative AF occurred in the first 3 hours after surgery. This was followed by a sharp decline in incidence over the next 24 hours. The second peak happened at postoperative day 2, followed by a more gradual tail off, Dr. Spencer J. Melby reported at the American Heart Association scientific sessions.
Ninety-six percent of all cases of postoperative AF in this retrospective chart review began within the first 7 days after surgery. Of the 423 patients who developed this common and vexing condition, 16% did so within the first 24 hours, 48% had their onset at 24-72 hours, and 36% did so after 72 hours, according to Dr. Melby, a cardiothoracic surgeon at the university.
In a multivariate analysis, the most potent risk factor for onset of postoperative AF during the first phase was mitral valve repair or replacement, which was associated with a 2.5-fold increased risk. The other significant risk factors for early-onset AF were older age – with 70-year-olds having a 1.6-fold greater risk than 50-year-olds – and longer ischemic time, with patients whose cross-clamp time was 70 minutes having a 1.3-fold greater risk compared with those who had a cross-clamp time of 35 minutes.
Advanced age was also a risk factor for late-phase onset of AF, but it was a stronger risk factor there than for early onset AF, with 70-year-olds being at threefold greater risk than 50-year-olds – nearly twice as great a risk as for early-onset postoperative AF. The other significant risk factors for late-phase postoperative AF in a multivariate analysis were white race, with a 1.9-fold increased risk, and heavier body weight, with patients weighing 100 kg being at 1.6-fold greater risk than those tipping the scales at 70 kg.
"We believe that these different risk factors at each time phase are indicative of change over time in the mechanisms that drive postoperative atrial fibrillation," the surgeon said.
The first peak may be the result of tissue trauma, which is typically greater with more complex operations having longer cross-clamp times. And mitral valve procedures often entail contact with the left atrium.
"We’ve found that in patients with onset in the second peak there’s a polymorphonuclear leukocyte riot going on in the pericardial space after surgery. Inflammation is high, oxidative stress is high. Troponin levels are extremely high in the pericardial fluid, so there are problems in the heart muscle itself. The body is trying to heal and may be overdoing it as reflected by the inflammation in that space," Dr. Melby explained.
Dr. Brendan M. Everett, session cochair, noted that postoperative day 2 is when a host of process-of-care issues potentially relevant to postoperative AF come into play.
"Postop day 2 is when pain control begins to slip a bit. Patients are mobilized, chest tubes are pulled. A lot of factors are going on that are very important overall to getting a patient up and out of the hospital but are serious stimuli – adrenergic and otherwise – that may force a patient to go into atrial fibrillation," observed Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.
Audience members praised Dr. Melby’s study as having "tremendous implications" for clinical practice, especially with regard to patient management guidelines. Dr. Melby noted that postoperative AF is a costly matter: It increases hospital length of stay by 1-2 days at a cost of roughly $10,000 per episode. Nationally, postoperative AF costs $4 billion per year.
Dr. Melby reported having no financial conflicts regarding his study.
AT THE AHA SCIENTIFIC SESSIONS
Major finding: The risk of new-onset postoperative atrial fibrillation is not constant over time; it peaks within the first 3 hours after surgery, falls off, then peaks again at postop day 2.
Data source: A retrospective chart review of 1,583 cardiac surgery patients at a single institution.
Disclosures: The presenter reported having no relevant financial interests.
Statins reduce recurrent thromboembolism risk
DALLAS – Current use of a statin was associated with significantly reduced risk of recurrent venous thromboembolism in a large national Danish observational study.
The fully adjusted 17% reduction in risk noted in statin users compared with nonusers was driven by a sharp reduction in the risk of recurrent deep venous thrombosis. In contrast, statin use provided no protection against recurrent pulmonary embolism, Dr. Morten Schmidt said at the American Heart Association scientific sessions.
He reported on all 40,780 Danish patients who experienced a first-ever venous thromboembolism (VTE) as recorded in the national hospital registry during 2004-2011.
Statin nonusers had close to an 8% cumulative incidence of recurrent VTE through 12 months of follow-up. The unadjusted risk of a recurrent VTE during months 3-12 after the initial event was 29% lower in current statin users as compared to nonusers. However, statin users were on average older and had a greater burden of comorbidities than nonusers. In a multivariate logistic regression analysis adjusted for these and other potential confounders, including aspirin or anticoagulant use, current statin use remained associated with a 17% lower relative risk of recurrent VTE, according to Dr. Schmidt of Aarhus (Denmark) University.
Current statin users had an unadjusted 48% reduction in the risk of deep venous thrombosis, which in a multivariate regression analysis was modified to a still-highly-significant 26% relative risk reduction.
Session cochair Dr. Brendan M. Everett commented that the results of the earlier landmark JUPITER trial support the Danish national observational study findings. In the nearly 19,000-subject, randomized, double-blind JUPITER study, subjects assigned to rosuvastatin had a highly significant 43% reduction in the risk of incident VTE during follow-up compared with placebo-treated controls. This was driven by a 55% reduction in the risk of incident deep venous thrombosis, with statin therapy having no significant effect on the risk of incident pulmonary embolism (N. Engl. J. Med. 2009;360:1851-61).
The JUPITER results strengthen the Danish study conclusions because JUPITER’s randomized design balances out inherent potential confounders in the observational study design, such as the possibility that statin-treated Danes with a first VTE might have received more comprehensive medical care, noted Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.
Dr. Schmidt reported having no financial conflicts of interest with regard to his study, which was funded by Danish scientific research grants.
DALLAS – Current use of a statin was associated with significantly reduced risk of recurrent venous thromboembolism in a large national Danish observational study.
The fully adjusted 17% reduction in risk noted in statin users compared with nonusers was driven by a sharp reduction in the risk of recurrent deep venous thrombosis. In contrast, statin use provided no protection against recurrent pulmonary embolism, Dr. Morten Schmidt said at the American Heart Association scientific sessions.
He reported on all 40,780 Danish patients who experienced a first-ever venous thromboembolism (VTE) as recorded in the national hospital registry during 2004-2011.
Statin nonusers had close to an 8% cumulative incidence of recurrent VTE through 12 months of follow-up. The unadjusted risk of a recurrent VTE during months 3-12 after the initial event was 29% lower in current statin users as compared to nonusers. However, statin users were on average older and had a greater burden of comorbidities than nonusers. In a multivariate logistic regression analysis adjusted for these and other potential confounders, including aspirin or anticoagulant use, current statin use remained associated with a 17% lower relative risk of recurrent VTE, according to Dr. Schmidt of Aarhus (Denmark) University.
Current statin users had an unadjusted 48% reduction in the risk of deep venous thrombosis, which in a multivariate regression analysis was modified to a still-highly-significant 26% relative risk reduction.
Session cochair Dr. Brendan M. Everett commented that the results of the earlier landmark JUPITER trial support the Danish national observational study findings. In the nearly 19,000-subject, randomized, double-blind JUPITER study, subjects assigned to rosuvastatin had a highly significant 43% reduction in the risk of incident VTE during follow-up compared with placebo-treated controls. This was driven by a 55% reduction in the risk of incident deep venous thrombosis, with statin therapy having no significant effect on the risk of incident pulmonary embolism (N. Engl. J. Med. 2009;360:1851-61).
The JUPITER results strengthen the Danish study conclusions because JUPITER’s randomized design balances out inherent potential confounders in the observational study design, such as the possibility that statin-treated Danes with a first VTE might have received more comprehensive medical care, noted Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.
Dr. Schmidt reported having no financial conflicts of interest with regard to his study, which was funded by Danish scientific research grants.
DALLAS – Current use of a statin was associated with significantly reduced risk of recurrent venous thromboembolism in a large national Danish observational study.
The fully adjusted 17% reduction in risk noted in statin users compared with nonusers was driven by a sharp reduction in the risk of recurrent deep venous thrombosis. In contrast, statin use provided no protection against recurrent pulmonary embolism, Dr. Morten Schmidt said at the American Heart Association scientific sessions.
He reported on all 40,780 Danish patients who experienced a first-ever venous thromboembolism (VTE) as recorded in the national hospital registry during 2004-2011.
Statin nonusers had close to an 8% cumulative incidence of recurrent VTE through 12 months of follow-up. The unadjusted risk of a recurrent VTE during months 3-12 after the initial event was 29% lower in current statin users as compared to nonusers. However, statin users were on average older and had a greater burden of comorbidities than nonusers. In a multivariate logistic regression analysis adjusted for these and other potential confounders, including aspirin or anticoagulant use, current statin use remained associated with a 17% lower relative risk of recurrent VTE, according to Dr. Schmidt of Aarhus (Denmark) University.
Current statin users had an unadjusted 48% reduction in the risk of deep venous thrombosis, which in a multivariate regression analysis was modified to a still-highly-significant 26% relative risk reduction.
Session cochair Dr. Brendan M. Everett commented that the results of the earlier landmark JUPITER trial support the Danish national observational study findings. In the nearly 19,000-subject, randomized, double-blind JUPITER study, subjects assigned to rosuvastatin had a highly significant 43% reduction in the risk of incident VTE during follow-up compared with placebo-treated controls. This was driven by a 55% reduction in the risk of incident deep venous thrombosis, with statin therapy having no significant effect on the risk of incident pulmonary embolism (N. Engl. J. Med. 2009;360:1851-61).
The JUPITER results strengthen the Danish study conclusions because JUPITER’s randomized design balances out inherent potential confounders in the observational study design, such as the possibility that statin-treated Danes with a first VTE might have received more comprehensive medical care, noted Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.
Dr. Schmidt reported having no financial conflicts of interest with regard to his study, which was funded by Danish scientific research grants.
AT THE AHA SCIENTIFIC SESSIONS
Major finding: Patients on statin therapy had an adjusted 17% lower risk of recurrent venous thromboembolism in the year following their first such event, compared with those not on a statin.
Data source: This was a retrospective observational study involving nearly 41,000 Danes who had a first venous thromboembolism during 2004-2011.
Disclosures: Dr. Schmidt reported having no financial conflicts of interest with regard to his study, which was funded by Danish scientific research grants.
Meta-analysis: Statins beneficial, even after age 75
DALLAS – Reassurance regarding the cardiovascular benefits of statin therapy in the elderly, even in those above age 75, is provided by a new meta-analysis by the international Cholesterol Treatment Trialists’ Collaboration.
The meta-analysis, which included 174,099 participants in 27 major, published, randomized controlled trials with a median follow-up of 4.9 years, should go a long way toward banishing physician and patient uncertainty about the appropriateness of statin therapy in the elderly. It’s evident that such uncertainty is widespread from recent studies indicating only about half of patients over age 65 are on statin therapy post myocardial infarction (MI). Moreover, the controversial new prevention guidelines don’t address the use of statins in patients over age 75, citing a lack of persuasive evidence because such patients were often excluded from participation in the major statin trials (J. Am. Coll. Cardiol. 2013 [doi: 10.1016/j.jacc.2013.11.002]).
Yet in the new meta-analysis by the University of Oxford–based Cholesterol Treatment Trialists’ Collaboration, 7% of all participants – that’s nearly 13,000 patients – were over age 75. That’s a large enough number to be able to draw tentative conclusions. In addition, another 33% of subjects in the meta-analysis were aged 66-75 years, Dr. Jordan Fulcher observed in presenting the results at the American Heart Association scientific sessions.
Dividing the nearly 175,000 subjects into four age groups – 55 and younger, 56-65, 66-75, and over 75 – it quickly became apparent to the investigators found that while statin therapy significantly reduced nonfatal MI, cardiovascular death, all-cause mortality, and major vascular events in each of the four age groups, there was also a significant trend for smaller relative risk reductions with advancing age. For example, the incidence of nonfatal MI or coronary heart disease (CHD) death in statin-treated patients aged 55 years or younger was 1.1%, compared with 1.5% in controls, for a 31% relative risk reduction per 39-mg/dL decrease in low-density lipoprotein (LDL) cholesterol, while in the over-75 group the rates were 2.8% versus 3.3%, for a less robust 24% relative risk reduction, reported Dr. Jordan Fulcher of the University of Sydney.
For major vascular events, whichis a broader are a compositeoutcome composed of nonfatal MI, CHD death, stroke, or coronary revascularization, patients aged 55 years or less who achieved a 39-mg/dL reduction in LDL had a 25% reduction compared with controls. This relative risk reduction waswhittled down to only 15% in the over-75 group after adjustment for baseline differences in hypertension, gender, diabetes, prior cardiovascular disease, smoking, and creatinine clearance.
Nonetheless – and this is a key study finding – because of the increasing absolute risk of major events with advancing age, the number needed to treat in order to prevent one additional event is "almost identical" across all age groups, Dr. Fulcher said.
"We therefore conclude that elderly patients at risk should be considered equally as younger patients for statin therapy," he said.
The meta-analysis showed no evidence of favorable or adverse effects of statin therapy on cancer incidence or mortality or on nonvascular mortality in any age group.
Session chair Dr. Lori Mosca said that "as a card-carrying epidemiologist," she thinks it’s important to emphasize for the benefit of nonepidemiologists the truism that relative risk reductions for effective therapies get smaller as people get older because the background rate of disease goes up.
"Relative risk is used for etiology. Absolute risk is used for treatment decisions. I don’t really care if the relative risk [reduction] gets lower as we get older. That has nothing to do with the importance of statins in older patients. It could potentially be more important to treat the elderly despite a lower relative risk" reduction, said Dr. Mosca, professor of medicine at Columbia University, New York, and director of preventive cardiology at New York–Presbyterian Hospital.
The Cholesterol Treatment Trialists’Collaboration was established back in 1994 in early recognition that no single statin megatrial would have sufficient size and statistical power to answer all the key future clinical issues to arise. The trialists’ database includes virtually all the landmark statin trials whose acronyms are household names within medicine.
Funding for the trialists’ongoing work is provided by the U.K. Medical Research Council and other national health research organizations. Dr. Fulcher reported having no financial conflicts of interest.
Dr. Jun Chiong, FCCP, comments: Strategies to prevent future cardiovascular events in adults aged >75 years should be individualized, but this study showed that the benefit of long-term statin therapy extends to this age group. Physicians still must balance the benefits of secondary atherosclerotic cardiovascular disease prevention with the risk it may carry in older adults. It’s still important to see future controlled studies that will clarify medication regimens, lifestyle modifications, and also revascularization strategies that will yield the greatest benefit/lowest risk in this rapidly expanding age group.
Dr. Jun Chiong, FCCP, comments: Strategies to prevent future cardiovascular events in adults aged >75 years should be individualized, but this study showed that the benefit of long-term statin therapy extends to this age group. Physicians still must balance the benefits of secondary atherosclerotic cardiovascular disease prevention with the risk it may carry in older adults. It’s still important to see future controlled studies that will clarify medication regimens, lifestyle modifications, and also revascularization strategies that will yield the greatest benefit/lowest risk in this rapidly expanding age group.
Dr. Jun Chiong, FCCP, comments: Strategies to prevent future cardiovascular events in adults aged >75 years should be individualized, but this study showed that the benefit of long-term statin therapy extends to this age group. Physicians still must balance the benefits of secondary atherosclerotic cardiovascular disease prevention with the risk it may carry in older adults. It’s still important to see future controlled studies that will clarify medication regimens, lifestyle modifications, and also revascularization strategies that will yield the greatest benefit/lowest risk in this rapidly expanding age group.
DALLAS – Reassurance regarding the cardiovascular benefits of statin therapy in the elderly, even in those above age 75, is provided by a new meta-analysis by the international Cholesterol Treatment Trialists’ Collaboration.
The meta-analysis, which included 174,099 participants in 27 major, published, randomized controlled trials with a median follow-up of 4.9 years, should go a long way toward banishing physician and patient uncertainty about the appropriateness of statin therapy in the elderly. It’s evident that such uncertainty is widespread from recent studies indicating only about half of patients over age 65 are on statin therapy post myocardial infarction (MI). Moreover, the controversial new prevention guidelines don’t address the use of statins in patients over age 75, citing a lack of persuasive evidence because such patients were often excluded from participation in the major statin trials (J. Am. Coll. Cardiol. 2013 [doi: 10.1016/j.jacc.2013.11.002]).
Yet in the new meta-analysis by the University of Oxford–based Cholesterol Treatment Trialists’ Collaboration, 7% of all participants – that’s nearly 13,000 patients – were over age 75. That’s a large enough number to be able to draw tentative conclusions. In addition, another 33% of subjects in the meta-analysis were aged 66-75 years, Dr. Jordan Fulcher observed in presenting the results at the American Heart Association scientific sessions.
Dividing the nearly 175,000 subjects into four age groups – 55 and younger, 56-65, 66-75, and over 75 – it quickly became apparent to the investigators found that while statin therapy significantly reduced nonfatal MI, cardiovascular death, all-cause mortality, and major vascular events in each of the four age groups, there was also a significant trend for smaller relative risk reductions with advancing age. For example, the incidence of nonfatal MI or coronary heart disease (CHD) death in statin-treated patients aged 55 years or younger was 1.1%, compared with 1.5% in controls, for a 31% relative risk reduction per 39-mg/dL decrease in low-density lipoprotein (LDL) cholesterol, while in the over-75 group the rates were 2.8% versus 3.3%, for a less robust 24% relative risk reduction, reported Dr. Jordan Fulcher of the University of Sydney.
For major vascular events, whichis a broader are a compositeoutcome composed of nonfatal MI, CHD death, stroke, or coronary revascularization, patients aged 55 years or less who achieved a 39-mg/dL reduction in LDL had a 25% reduction compared with controls. This relative risk reduction waswhittled down to only 15% in the over-75 group after adjustment for baseline differences in hypertension, gender, diabetes, prior cardiovascular disease, smoking, and creatinine clearance.
Nonetheless – and this is a key study finding – because of the increasing absolute risk of major events with advancing age, the number needed to treat in order to prevent one additional event is "almost identical" across all age groups, Dr. Fulcher said.
"We therefore conclude that elderly patients at risk should be considered equally as younger patients for statin therapy," he said.
The meta-analysis showed no evidence of favorable or adverse effects of statin therapy on cancer incidence or mortality or on nonvascular mortality in any age group.
Session chair Dr. Lori Mosca said that "as a card-carrying epidemiologist," she thinks it’s important to emphasize for the benefit of nonepidemiologists the truism that relative risk reductions for effective therapies get smaller as people get older because the background rate of disease goes up.
"Relative risk is used for etiology. Absolute risk is used for treatment decisions. I don’t really care if the relative risk [reduction] gets lower as we get older. That has nothing to do with the importance of statins in older patients. It could potentially be more important to treat the elderly despite a lower relative risk" reduction, said Dr. Mosca, professor of medicine at Columbia University, New York, and director of preventive cardiology at New York–Presbyterian Hospital.
The Cholesterol Treatment Trialists’Collaboration was established back in 1994 in early recognition that no single statin megatrial would have sufficient size and statistical power to answer all the key future clinical issues to arise. The trialists’ database includes virtually all the landmark statin trials whose acronyms are household names within medicine.
Funding for the trialists’ongoing work is provided by the U.K. Medical Research Council and other national health research organizations. Dr. Fulcher reported having no financial conflicts of interest.
DALLAS – Reassurance regarding the cardiovascular benefits of statin therapy in the elderly, even in those above age 75, is provided by a new meta-analysis by the international Cholesterol Treatment Trialists’ Collaboration.
The meta-analysis, which included 174,099 participants in 27 major, published, randomized controlled trials with a median follow-up of 4.9 years, should go a long way toward banishing physician and patient uncertainty about the appropriateness of statin therapy in the elderly. It’s evident that such uncertainty is widespread from recent studies indicating only about half of patients over age 65 are on statin therapy post myocardial infarction (MI). Moreover, the controversial new prevention guidelines don’t address the use of statins in patients over age 75, citing a lack of persuasive evidence because such patients were often excluded from participation in the major statin trials (J. Am. Coll. Cardiol. 2013 [doi: 10.1016/j.jacc.2013.11.002]).
Yet in the new meta-analysis by the University of Oxford–based Cholesterol Treatment Trialists’ Collaboration, 7% of all participants – that’s nearly 13,000 patients – were over age 75. That’s a large enough number to be able to draw tentative conclusions. In addition, another 33% of subjects in the meta-analysis were aged 66-75 years, Dr. Jordan Fulcher observed in presenting the results at the American Heart Association scientific sessions.
Dividing the nearly 175,000 subjects into four age groups – 55 and younger, 56-65, 66-75, and over 75 – it quickly became apparent to the investigators found that while statin therapy significantly reduced nonfatal MI, cardiovascular death, all-cause mortality, and major vascular events in each of the four age groups, there was also a significant trend for smaller relative risk reductions with advancing age. For example, the incidence of nonfatal MI or coronary heart disease (CHD) death in statin-treated patients aged 55 years or younger was 1.1%, compared with 1.5% in controls, for a 31% relative risk reduction per 39-mg/dL decrease in low-density lipoprotein (LDL) cholesterol, while in the over-75 group the rates were 2.8% versus 3.3%, for a less robust 24% relative risk reduction, reported Dr. Jordan Fulcher of the University of Sydney.
For major vascular events, whichis a broader are a compositeoutcome composed of nonfatal MI, CHD death, stroke, or coronary revascularization, patients aged 55 years or less who achieved a 39-mg/dL reduction in LDL had a 25% reduction compared with controls. This relative risk reduction waswhittled down to only 15% in the over-75 group after adjustment for baseline differences in hypertension, gender, diabetes, prior cardiovascular disease, smoking, and creatinine clearance.
Nonetheless – and this is a key study finding – because of the increasing absolute risk of major events with advancing age, the number needed to treat in order to prevent one additional event is "almost identical" across all age groups, Dr. Fulcher said.
"We therefore conclude that elderly patients at risk should be considered equally as younger patients for statin therapy," he said.
The meta-analysis showed no evidence of favorable or adverse effects of statin therapy on cancer incidence or mortality or on nonvascular mortality in any age group.
Session chair Dr. Lori Mosca said that "as a card-carrying epidemiologist," she thinks it’s important to emphasize for the benefit of nonepidemiologists the truism that relative risk reductions for effective therapies get smaller as people get older because the background rate of disease goes up.
"Relative risk is used for etiology. Absolute risk is used for treatment decisions. I don’t really care if the relative risk [reduction] gets lower as we get older. That has nothing to do with the importance of statins in older patients. It could potentially be more important to treat the elderly despite a lower relative risk" reduction, said Dr. Mosca, professor of medicine at Columbia University, New York, and director of preventive cardiology at New York–Presbyterian Hospital.
The Cholesterol Treatment Trialists’Collaboration was established back in 1994 in early recognition that no single statin megatrial would have sufficient size and statistical power to answer all the key future clinical issues to arise. The trialists’ database includes virtually all the landmark statin trials whose acronyms are household names within medicine.
Funding for the trialists’ongoing work is provided by the U.K. Medical Research Council and other national health research organizations. Dr. Fulcher reported having no financial conflicts of interest.
Major finding: While the relative risk reduction provided by statin therapy in patients over age 75 is smaller than in younger age groups, the number needed to treat in order to prevent one major vascular event is virtually identical across the full age spectrum due to the increasing absolute risk of vascular disease with advancing age.
Data source: A meta-analysis of 27 major randomized controlled clinical trials of statin therapy with 174,099 participants.
Disclosures: Funding for the trialists’ ongoing work is provided by the U.K. Medical Research Council and other national health research organizations. Dr. Fulcher reported having no financial conflicts of interest.
In the real world, persistence on warfarin is low
DALLAS – Less than half of patients with a first venous thromboembolism in real-world clinical practice started on warfarin within 10 days after the event, according to a large U.S. study.
Among those who did start, three-quarters discontinued use of the anticoagulant within 1 year.
"Effective and convenient anticoagulants with significant reduction in bleeding risk are needed for long-term treatment of venous thromboembolism and prevention of VTE recurrence," Dr. Xianchen Liu said at the American Heart Association scientific sessions.
Dr. Liu, director of global health economics and outcomes research at Pfizer, presented an analysis of 153,809 adults with a first deep venous thrombosis and/or pulmonary embolus was recorded in the Truven Health MarketScan Commercial and Medicare Supplemental databases. Within 10 days of diagnosis, 46% were treated with warfarin.
Dr. Liu focused on the 39,719 patients with at least 1 year of follow-up, of whom 73% had DVT as their index VTE, 24% had a pulmonary embolism, and 3% had both.
Nearly one in four patients who started on warfarin within 10 days after their index VTE discontinued the anticoagulant after 3 months, 47% after 6 months, and 75% within 1 year. The average treatment duration was 5 months, according to Dr. Liu.
Factors linked to reduced likelihood of warfarin discontinuation included comorbid atrial fibrillation, which was associated with a 25% reduction in risk of discontinuation; thrombophilia, with a 34% relative risk reduction; and pulmonary embolism, with a 24% reduction in discontinuation compared to patients with DVT only.
On the other hand, history of fracture, pregnancy, hormone therapy, or major bleeding within 6 months prior to the index VTE was associated with 24%, 35%, 13%, and 9% increased risks for warfarin discontinuation, respectively.
The clinical importance of these observations lies in the fact that roughly 900,000 incident cases of VTE occur annually in the United States. It is the most common preventable cause of death in hospitalized patients. Indeed, 2%-10% of all hospital deaths are attributed to pulmonary embolism. The VTE recurrence rate is 7%-14% within 1 year, Dr. Liu said.
Pfizer is codeveloper of the novel oral anticoagulant apixaban. Dr. Liu’s MarketScan study is based on data from 2006-2011, before novel anticoagulants became available.
Stroke prevention’s ‘major problem’
In a separate presentation, Dr. Geoffrey D. Barnes called poor warfarin persistence for stroke prevention in patients with atrial fibrillation "a major problem," citing the 38% probability of discontinuation within 1 year in his study of patients started on the drug for this indication at seven anticoagulation clinics participating in the Michigan Anticoagulation Quality Improvement Initiative.
A silver lining: One-year persistence with warfarin therapy was significantly associated with increasing CHADS2 scores. The 1-year persistence rate among the 1,901 subjects was 29% in those with a CHADS2 score of 0, 56% with a CHADS2 of 1, and 71% in those with a high CHADS2 of 2-6.
In contrast, bleeding risk as determined by baseline HAS-BLED score was unrelated to warfarin persistence, said Dr. Barnes, a cardiologist at the University of Michigan, Ann Arbor.
He reported that 85% of the Michigan patients with atrial fibrillation who discontinued warfarin did so for a known reason. That reason was a bleeding event in 8.3% of cases, change in bleeding risk in 4.7%, death in 9.5%, and ‘indication resolved’ in two-thirds of discontinuations. The likelihood of warfarin discontinuation was particularly high in patients who underwent cardioversion or catheter ablation, even though the implications of those procedures in terms of stroke risk are unresolved.
The ongoing Michigan Anticoagulation Quality Improvement Initiative is funded by Blue Cross Blue Shield of Michigan. Dr. Barnes reported having no financial conflicts of interest.
DALLAS – Less than half of patients with a first venous thromboembolism in real-world clinical practice started on warfarin within 10 days after the event, according to a large U.S. study.
Among those who did start, three-quarters discontinued use of the anticoagulant within 1 year.
"Effective and convenient anticoagulants with significant reduction in bleeding risk are needed for long-term treatment of venous thromboembolism and prevention of VTE recurrence," Dr. Xianchen Liu said at the American Heart Association scientific sessions.
Dr. Liu, director of global health economics and outcomes research at Pfizer, presented an analysis of 153,809 adults with a first deep venous thrombosis and/or pulmonary embolus was recorded in the Truven Health MarketScan Commercial and Medicare Supplemental databases. Within 10 days of diagnosis, 46% were treated with warfarin.
Dr. Liu focused on the 39,719 patients with at least 1 year of follow-up, of whom 73% had DVT as their index VTE, 24% had a pulmonary embolism, and 3% had both.
Nearly one in four patients who started on warfarin within 10 days after their index VTE discontinued the anticoagulant after 3 months, 47% after 6 months, and 75% within 1 year. The average treatment duration was 5 months, according to Dr. Liu.
Factors linked to reduced likelihood of warfarin discontinuation included comorbid atrial fibrillation, which was associated with a 25% reduction in risk of discontinuation; thrombophilia, with a 34% relative risk reduction; and pulmonary embolism, with a 24% reduction in discontinuation compared to patients with DVT only.
On the other hand, history of fracture, pregnancy, hormone therapy, or major bleeding within 6 months prior to the index VTE was associated with 24%, 35%, 13%, and 9% increased risks for warfarin discontinuation, respectively.
The clinical importance of these observations lies in the fact that roughly 900,000 incident cases of VTE occur annually in the United States. It is the most common preventable cause of death in hospitalized patients. Indeed, 2%-10% of all hospital deaths are attributed to pulmonary embolism. The VTE recurrence rate is 7%-14% within 1 year, Dr. Liu said.
Pfizer is codeveloper of the novel oral anticoagulant apixaban. Dr. Liu’s MarketScan study is based on data from 2006-2011, before novel anticoagulants became available.
Stroke prevention’s ‘major problem’
In a separate presentation, Dr. Geoffrey D. Barnes called poor warfarin persistence for stroke prevention in patients with atrial fibrillation "a major problem," citing the 38% probability of discontinuation within 1 year in his study of patients started on the drug for this indication at seven anticoagulation clinics participating in the Michigan Anticoagulation Quality Improvement Initiative.
A silver lining: One-year persistence with warfarin therapy was significantly associated with increasing CHADS2 scores. The 1-year persistence rate among the 1,901 subjects was 29% in those with a CHADS2 score of 0, 56% with a CHADS2 of 1, and 71% in those with a high CHADS2 of 2-6.
In contrast, bleeding risk as determined by baseline HAS-BLED score was unrelated to warfarin persistence, said Dr. Barnes, a cardiologist at the University of Michigan, Ann Arbor.
He reported that 85% of the Michigan patients with atrial fibrillation who discontinued warfarin did so for a known reason. That reason was a bleeding event in 8.3% of cases, change in bleeding risk in 4.7%, death in 9.5%, and ‘indication resolved’ in two-thirds of discontinuations. The likelihood of warfarin discontinuation was particularly high in patients who underwent cardioversion or catheter ablation, even though the implications of those procedures in terms of stroke risk are unresolved.
The ongoing Michigan Anticoagulation Quality Improvement Initiative is funded by Blue Cross Blue Shield of Michigan. Dr. Barnes reported having no financial conflicts of interest.
DALLAS – Less than half of patients with a first venous thromboembolism in real-world clinical practice started on warfarin within 10 days after the event, according to a large U.S. study.
Among those who did start, three-quarters discontinued use of the anticoagulant within 1 year.
"Effective and convenient anticoagulants with significant reduction in bleeding risk are needed for long-term treatment of venous thromboembolism and prevention of VTE recurrence," Dr. Xianchen Liu said at the American Heart Association scientific sessions.
Dr. Liu, director of global health economics and outcomes research at Pfizer, presented an analysis of 153,809 adults with a first deep venous thrombosis and/or pulmonary embolus was recorded in the Truven Health MarketScan Commercial and Medicare Supplemental databases. Within 10 days of diagnosis, 46% were treated with warfarin.
Dr. Liu focused on the 39,719 patients with at least 1 year of follow-up, of whom 73% had DVT as their index VTE, 24% had a pulmonary embolism, and 3% had both.
Nearly one in four patients who started on warfarin within 10 days after their index VTE discontinued the anticoagulant after 3 months, 47% after 6 months, and 75% within 1 year. The average treatment duration was 5 months, according to Dr. Liu.
Factors linked to reduced likelihood of warfarin discontinuation included comorbid atrial fibrillation, which was associated with a 25% reduction in risk of discontinuation; thrombophilia, with a 34% relative risk reduction; and pulmonary embolism, with a 24% reduction in discontinuation compared to patients with DVT only.
On the other hand, history of fracture, pregnancy, hormone therapy, or major bleeding within 6 months prior to the index VTE was associated with 24%, 35%, 13%, and 9% increased risks for warfarin discontinuation, respectively.
The clinical importance of these observations lies in the fact that roughly 900,000 incident cases of VTE occur annually in the United States. It is the most common preventable cause of death in hospitalized patients. Indeed, 2%-10% of all hospital deaths are attributed to pulmonary embolism. The VTE recurrence rate is 7%-14% within 1 year, Dr. Liu said.
Pfizer is codeveloper of the novel oral anticoagulant apixaban. Dr. Liu’s MarketScan study is based on data from 2006-2011, before novel anticoagulants became available.
Stroke prevention’s ‘major problem’
In a separate presentation, Dr. Geoffrey D. Barnes called poor warfarin persistence for stroke prevention in patients with atrial fibrillation "a major problem," citing the 38% probability of discontinuation within 1 year in his study of patients started on the drug for this indication at seven anticoagulation clinics participating in the Michigan Anticoagulation Quality Improvement Initiative.
A silver lining: One-year persistence with warfarin therapy was significantly associated with increasing CHADS2 scores. The 1-year persistence rate among the 1,901 subjects was 29% in those with a CHADS2 score of 0, 56% with a CHADS2 of 1, and 71% in those with a high CHADS2 of 2-6.
In contrast, bleeding risk as determined by baseline HAS-BLED score was unrelated to warfarin persistence, said Dr. Barnes, a cardiologist at the University of Michigan, Ann Arbor.
He reported that 85% of the Michigan patients with atrial fibrillation who discontinued warfarin did so for a known reason. That reason was a bleeding event in 8.3% of cases, change in bleeding risk in 4.7%, death in 9.5%, and ‘indication resolved’ in two-thirds of discontinuations. The likelihood of warfarin discontinuation was particularly high in patients who underwent cardioversion or catheter ablation, even though the implications of those procedures in terms of stroke risk are unresolved.
The ongoing Michigan Anticoagulation Quality Improvement Initiative is funded by Blue Cross Blue Shield of Michigan. Dr. Barnes reported having no financial conflicts of interest.
AT THE AHA SCIENTIFIC SESSIONS
Major finding: Less than one-half of patients with a first VTE started on warfarin within 10 days; of those who did, nearly 75% discontinued therapy within 1 year. In a separate study, 38% of Michigan patients with AF placed on warfarin for stroke prevention discontinued treatment within 1 year.
Data source: The VTE study included nearly data from 40,000 patients placed on warfarin within 10 days after the index event and followed for at least 1 year. The atrial fibrillation study included 1,901 patients placed on warfarin for stroke prevention.
Disclosures: The VTE study was funded by Pfizer and presented by a company executive. The AF study was conducted by the Michigan Anticoagulation Quality Improvement Initiative and presented by a cardiologist without financial conflicts of interest.
CV risk in former light smokers reduced sooner than in heavy smokers
DALLAS – Older people who quit their moderate smoking habit reduced their cigarette-associated cardiovascular risks to the level seen people who had never smoked in as little as 8 years, according to a prospective population study.
This risk reversal occurred much sooner than the 15 years predicted in a 2004 report by the U.S. Surgeon General. This is yet another study to highlight the cardiovascular benefits of smoking cessation, and the message remains the same: "If you’re not a smoker, don’t start. And if you’re a smoker, quit, and quit early," said Dr. Ali Ahmed, professor of cardiovascular disease and gerontology, geriatrics, and palliative care at the University of Alabama at Birmingham and professor of epidemiology at the School of Public Health there. He presented his study at the American Heart Association’s annual scientific sessions.
They narrowed down the Cardiovascular Health Study population to 3,409 adults, 65 years and older, who were free of baseline heart failure. Of the 850 former smokers, roughly 320 had smoked less than 32 pack-years. They had quit within the past 15 years, with the median of 8 years.
Adjusted and age-sex-race adjusted findings during 13 years of follow-up showed that the risk of incident heart failure and cardiovascular mortality were similar between former light smokers and never-smokers.
The light smokers, defined as individuals smoking less than 32 pack-years, who quit smoking less than 15 years ago, had an 18% risk of incident heart failure, compared with 21% in never-smoker; and 14% risk of cardiovascular mortality, compared with 17% in never-smokers. However, their risk of all-cause and noncardiovascular mortality remained significantly higher than in never-smokers.
In previous studies, Dr. Ahmed and his associates had shown that former heavy smokers (32 or more pack-years) may be at increased risk of cardiovascular disease, even after 15 years. (Circulation 2010;122:A17788; Circulation 2011;124:A18263). The team wanted to find out whether smoking less than 32 pack-years would mean earlier reversal of cardiovascular risk.
Dr. Ahmed said that the cardiovascular benefits of quitting smoking, which – unlike mutations or damage to alveolar lining – is reversible, begins within 24 hours after cessation, unless the damage has reached a threshold of no return from heavy smoking.
Dr. Ahmed had no disclosures.
On Twitter @NaseemSMiller
DALLAS – Older people who quit their moderate smoking habit reduced their cigarette-associated cardiovascular risks to the level seen people who had never smoked in as little as 8 years, according to a prospective population study.
This risk reversal occurred much sooner than the 15 years predicted in a 2004 report by the U.S. Surgeon General. This is yet another study to highlight the cardiovascular benefits of smoking cessation, and the message remains the same: "If you’re not a smoker, don’t start. And if you’re a smoker, quit, and quit early," said Dr. Ali Ahmed, professor of cardiovascular disease and gerontology, geriatrics, and palliative care at the University of Alabama at Birmingham and professor of epidemiology at the School of Public Health there. He presented his study at the American Heart Association’s annual scientific sessions.
They narrowed down the Cardiovascular Health Study population to 3,409 adults, 65 years and older, who were free of baseline heart failure. Of the 850 former smokers, roughly 320 had smoked less than 32 pack-years. They had quit within the past 15 years, with the median of 8 years.
Adjusted and age-sex-race adjusted findings during 13 years of follow-up showed that the risk of incident heart failure and cardiovascular mortality were similar between former light smokers and never-smokers.
The light smokers, defined as individuals smoking less than 32 pack-years, who quit smoking less than 15 years ago, had an 18% risk of incident heart failure, compared with 21% in never-smoker; and 14% risk of cardiovascular mortality, compared with 17% in never-smokers. However, their risk of all-cause and noncardiovascular mortality remained significantly higher than in never-smokers.
In previous studies, Dr. Ahmed and his associates had shown that former heavy smokers (32 or more pack-years) may be at increased risk of cardiovascular disease, even after 15 years. (Circulation 2010;122:A17788; Circulation 2011;124:A18263). The team wanted to find out whether smoking less than 32 pack-years would mean earlier reversal of cardiovascular risk.
Dr. Ahmed said that the cardiovascular benefits of quitting smoking, which – unlike mutations or damage to alveolar lining – is reversible, begins within 24 hours after cessation, unless the damage has reached a threshold of no return from heavy smoking.
Dr. Ahmed had no disclosures.
On Twitter @NaseemSMiller
DALLAS – Older people who quit their moderate smoking habit reduced their cigarette-associated cardiovascular risks to the level seen people who had never smoked in as little as 8 years, according to a prospective population study.
This risk reversal occurred much sooner than the 15 years predicted in a 2004 report by the U.S. Surgeon General. This is yet another study to highlight the cardiovascular benefits of smoking cessation, and the message remains the same: "If you’re not a smoker, don’t start. And if you’re a smoker, quit, and quit early," said Dr. Ali Ahmed, professor of cardiovascular disease and gerontology, geriatrics, and palliative care at the University of Alabama at Birmingham and professor of epidemiology at the School of Public Health there. He presented his study at the American Heart Association’s annual scientific sessions.
They narrowed down the Cardiovascular Health Study population to 3,409 adults, 65 years and older, who were free of baseline heart failure. Of the 850 former smokers, roughly 320 had smoked less than 32 pack-years. They had quit within the past 15 years, with the median of 8 years.
Adjusted and age-sex-race adjusted findings during 13 years of follow-up showed that the risk of incident heart failure and cardiovascular mortality were similar between former light smokers and never-smokers.
The light smokers, defined as individuals smoking less than 32 pack-years, who quit smoking less than 15 years ago, had an 18% risk of incident heart failure, compared with 21% in never-smoker; and 14% risk of cardiovascular mortality, compared with 17% in never-smokers. However, their risk of all-cause and noncardiovascular mortality remained significantly higher than in never-smokers.
In previous studies, Dr. Ahmed and his associates had shown that former heavy smokers (32 or more pack-years) may be at increased risk of cardiovascular disease, even after 15 years. (Circulation 2010;122:A17788; Circulation 2011;124:A18263). The team wanted to find out whether smoking less than 32 pack-years would mean earlier reversal of cardiovascular risk.
Dr. Ahmed said that the cardiovascular benefits of quitting smoking, which – unlike mutations or damage to alveolar lining – is reversible, begins within 24 hours after cessation, unless the damage has reached a threshold of no return from heavy smoking.
Dr. Ahmed had no disclosures.
On Twitter @NaseemSMiller
AT THE 2013 AHA SCIENTIFIC SESSIONS
Major finding: Former smokers with less than 32 pack-years had a 14% risk of CV death, compared with 17% in never-smokers. (P = .691)
Data source: Prospective analysis of data from the Cardiovascular Health Study.
Disclosures: Dr. Ahmed had no disclosures.
Ten-year outcomes for ablation in atrial fibrillation impressive
DALLAS – At 10 years after their procedures, the rate of freedom from atrial fibrillation and atrial tachycardia was 87% in 513 patients who underwent pulmonary vein antrum isolation for drug-refractory paroxysmal atrial fibrillation at a single high-volume center in Texas.
After a single radiofrequency ablation procedure, 59% of patients remained arrhythmia free for the full decade and another 28% of the cohort was rendered arrhythmia free after an average of two repeat ablation procedures, Dr. Pasquale Santangeli reported at the American Heart Association scientific sessions.
A particularly striking finding in this series was the low 4% rate of recurrent atrial arrhythmias during years 3-6 of follow-up, and the 5% rate between years 6 and 10. Those late recurrence rates are much lower than those in previous reports from other centers. The likely explanation lies in the fact that electrophysiologists at the Austin center routinely extended their pulmonary vein antrum isolation to the posterior wall and performed empiric isolation of the superior vena cava in all patients. Other centers reporting long-term outcomes generally performed segmental or less extensive antral isolation, observed Dr. Santangeli of the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin, Tex., and the University of Foggia (Italy).
Follow-up, including Holter monitoring, was performed every 3 months during year 1 and every 6-9 months thereafter. The rate of recurrent atrial arrhythmia was 21% at 1 year and 11% during years 1-3.
All patients with a recurrence were offered a repeat procedure, and 74% of them underwent repeat ablation. Reconnection in the pulmonary vein antrum was found in 31% of patients at the time of their first repeat procedure and in no patients who underwent a second repeat ablation.
Patients with recurrent atrial arrhythmia after two failed procedures underwent a high-dose isoproterenol challenge to identify nonpulmonary vein triggers, which were then targeted for ablation. The predictors of very late recurrence due to nonpulmonary vein triggers were increased left atrial size, obesity, and female gender.
Dr. Santangeli reported having no financial conflicts in connection with this study, which was honored as the top presentation by an early career investigator in the core area of heart rhythm disorders and resuscitation science at the annual meeting.
DALLAS – At 10 years after their procedures, the rate of freedom from atrial fibrillation and atrial tachycardia was 87% in 513 patients who underwent pulmonary vein antrum isolation for drug-refractory paroxysmal atrial fibrillation at a single high-volume center in Texas.
After a single radiofrequency ablation procedure, 59% of patients remained arrhythmia free for the full decade and another 28% of the cohort was rendered arrhythmia free after an average of two repeat ablation procedures, Dr. Pasquale Santangeli reported at the American Heart Association scientific sessions.
A particularly striking finding in this series was the low 4% rate of recurrent atrial arrhythmias during years 3-6 of follow-up, and the 5% rate between years 6 and 10. Those late recurrence rates are much lower than those in previous reports from other centers. The likely explanation lies in the fact that electrophysiologists at the Austin center routinely extended their pulmonary vein antrum isolation to the posterior wall and performed empiric isolation of the superior vena cava in all patients. Other centers reporting long-term outcomes generally performed segmental or less extensive antral isolation, observed Dr. Santangeli of the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin, Tex., and the University of Foggia (Italy).
Follow-up, including Holter monitoring, was performed every 3 months during year 1 and every 6-9 months thereafter. The rate of recurrent atrial arrhythmia was 21% at 1 year and 11% during years 1-3.
All patients with a recurrence were offered a repeat procedure, and 74% of them underwent repeat ablation. Reconnection in the pulmonary vein antrum was found in 31% of patients at the time of their first repeat procedure and in no patients who underwent a second repeat ablation.
Patients with recurrent atrial arrhythmia after two failed procedures underwent a high-dose isoproterenol challenge to identify nonpulmonary vein triggers, which were then targeted for ablation. The predictors of very late recurrence due to nonpulmonary vein triggers were increased left atrial size, obesity, and female gender.
Dr. Santangeli reported having no financial conflicts in connection with this study, which was honored as the top presentation by an early career investigator in the core area of heart rhythm disorders and resuscitation science at the annual meeting.
DALLAS – At 10 years after their procedures, the rate of freedom from atrial fibrillation and atrial tachycardia was 87% in 513 patients who underwent pulmonary vein antrum isolation for drug-refractory paroxysmal atrial fibrillation at a single high-volume center in Texas.
After a single radiofrequency ablation procedure, 59% of patients remained arrhythmia free for the full decade and another 28% of the cohort was rendered arrhythmia free after an average of two repeat ablation procedures, Dr. Pasquale Santangeli reported at the American Heart Association scientific sessions.
A particularly striking finding in this series was the low 4% rate of recurrent atrial arrhythmias during years 3-6 of follow-up, and the 5% rate between years 6 and 10. Those late recurrence rates are much lower than those in previous reports from other centers. The likely explanation lies in the fact that electrophysiologists at the Austin center routinely extended their pulmonary vein antrum isolation to the posterior wall and performed empiric isolation of the superior vena cava in all patients. Other centers reporting long-term outcomes generally performed segmental or less extensive antral isolation, observed Dr. Santangeli of the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin, Tex., and the University of Foggia (Italy).
Follow-up, including Holter monitoring, was performed every 3 months during year 1 and every 6-9 months thereafter. The rate of recurrent atrial arrhythmia was 21% at 1 year and 11% during years 1-3.
All patients with a recurrence were offered a repeat procedure, and 74% of them underwent repeat ablation. Reconnection in the pulmonary vein antrum was found in 31% of patients at the time of their first repeat procedure and in no patients who underwent a second repeat ablation.
Patients with recurrent atrial arrhythmia after two failed procedures underwent a high-dose isoproterenol challenge to identify nonpulmonary vein triggers, which were then targeted for ablation. The predictors of very late recurrence due to nonpulmonary vein triggers were increased left atrial size, obesity, and female gender.
Dr. Santangeli reported having no financial conflicts in connection with this study, which was honored as the top presentation by an early career investigator in the core area of heart rhythm disorders and resuscitation science at the annual meeting.
AT THE AHA SCIENTIFIC SESSIONS
Major finding: A decade after 513 patients underwent extensive pulmonary vein antrum isolation for drug-resistant paroxysmal atrial fibrillation, 87% were free of atrial fibrillation/atrial tachycardia, including 59% with single-procedure arrhythmia-free survival.
Data source: A retrospective case series involving 513 patients who underwent pulmonary vein antrum isolation during 2000-2002 at a single high-volume center.
Disclosures: The presenter reported having no financial conflicts.