Acquired Cardiovascular Disease

CHICAGO – Absence of coronary artery calcium upon imaging results in an impressively low cardiovascular event rate over the next 10 years regardless of an individual’s level of standard risk factors, according to prospective data from the MESA study.

In contrast, a coronary artery calcium (CAC) score of 1-10, often described as minimal CAC, nearly doubles the 10-year risk, compared with a baseline CAC score of 0.

Prior to these new 10-year data, many cardiologists considered a CAC score of 1-10 as tantamount to no CAC. Not so, Dr. Parag H. Joshi said at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

“A CAC of 0 is presumably identifying someone without any atherosclerosis. Just the presence of minimal calcium suggests that atherosclerosis is building up. Our data suggest that among individuals with a CAC of 1-10, current smoking, elevated non-HDL cholesterol, and particularly hypertension should be treated aggressively,” said Dr. Joshi, a clinical fellow in cardiovascular diseases and prevention at Johns Hopkins University, Baltimore.

Prior studies totaling more than 50,000 subjects with a CAC score of 0 have shown very low cardiovascular event rates over 4-5 years of follow-up. However, current cardiovascular risk estimates focus on 10-year risk. This new analysis from MESA (Multi-Ethnic Study of Atherosclerosis) is the first study to provide prospective, 10-year events data, and those data are highly reassuring, he added.

MESA is a prospective, population-based cohort study. This analysis included 6,814 subjects aged 45-84 who were free of clinical cardiovascular disease at baseline, when their CAC score was determined. At that time, 3,415 participants had a CAC score of 0 and 508 had a score of 1-10.

During a median 10.3 years of follow-up, 123 cardiovascular events occurred, roughly one-third of which were nonfatal acute MIs and half of which were nonfatal strokes; the remainder were cardiovascular deaths.

The event rate was 2.9/1,000 person-years in subjects with a CAC of 0 and significantly greater at 5.5/1,000 person-years with a score of 1-10. However, since the cardiovascular risk factor profile of the zero CAC group was generally more favorable, Dr. Joshi and coinvestigators carried out a Cox proportional hazards analysis factoring in demographics, standard cardiovascular risk factors, body mass index, C-reactive protein level, and carotid intima media thickness. The adjusted 10-year event risk in the group with a CAC score of 1-10 was 1.9-fold greater than with a CAC of 0.

The highest 10-year event rate was noted in subjects with at least three of the following four risk factors at baseline: hypertension, current smoking, diabetes, and hyperlipidemia. The rate was 6.5/1,000 person-years in such individuals if they had a CAC of 0 and doubled at 13.1/1,000 person-years with a score of 1-10.

In a multivariate Cox analysis, age, smoking, and hypertension proved to be significant predictors of cardiovascular events in the group with a CAC of 0 as well as in those with a CAC of 1-10. But there was one important difference between the two groups: While the hazard ratio for cardiovascular events associated with hypertension versus no hypertension was 2.1 in subjects with a CAC of 0, the presence of hypertension in individuals with a CAC of 1-10 increased their event risk by 10.2-fold, or nearly five times greater than the risk increase associated with hypertension in persons with a CAC of 0, Dr. Joshi observed.

Non–HDL cholesterol level was predictive of cardiovascular risk in subjects with a CAC of 1-10 but not in those with a score of 0.

When actual event rates were compared with those predicted by the atherosclerotic cardiovascular disease (ASCVD) risk estimator introduced in the 2013 AHA/American College of Cardiology cholesterol guidelines, the event rate in subjects with an ASCVD 10-year risk estimate of 7.5%-15% but a CAC of 0 was just 4.4%.

Audience members noted that CAC scores didn’t do a very good job of stratifying stroke risk in MESA. That’s not surprising, since the score reflects coronary but not carotid artery calcium. But it is a limitation of CAC as a predictive tool, especially in light of the fact that strokes accounted for half of all cardiovascular events in the study.

Asked where he and his coinvestigators plan to go from here, Dr. Joshi said a randomized, controlled trial would be ideal, but to date funding isn’t available. However, the observational data from MESA and other studies suggest such a trial may not even be needed.

“Certainly the guidelines do allow for CAC scoring to be used in clinical decision making,” he noted.

The MESA study is funded by the National Heart, Lung, and Blood Institute. Dr. Joshi reported having no financial conflicts.

[email protected]

CHICAGO – Absence of coronary artery calcium upon imaging results in an impressively low cardiovascular event rate over the next 10 years regardless of an individual’s level of standard risk factors, according to prospective data from the MESA study.

In contrast, a coronary artery calcium (CAC) score of 1-10, often described as minimal CAC, nearly doubles the 10-year risk, compared with a baseline CAC score of 0.

Prior to these new 10-year data, many cardiologists considered a CAC score of 1-10 as tantamount to no CAC. Not so, Dr. Parag H. Joshi said at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

“A CAC of 0 is presumably identifying someone without any atherosclerosis. Just the presence of minimal calcium suggests that atherosclerosis is building up. Our data suggest that among individuals with a CAC of 1-10, current smoking, elevated non-HDL cholesterol, and particularly hypertension should be treated aggressively,” said Dr. Joshi, a clinical fellow in cardiovascular diseases and prevention at Johns Hopkins University, Baltimore.

Prior studies totaling more than 50,000 subjects with a CAC score of 0 have shown very low cardiovascular event rates over 4-5 years of follow-up. However, current cardiovascular risk estimates focus on 10-year risk. This new analysis from MESA (Multi-Ethnic Study of Atherosclerosis) is the first study to provide prospective, 10-year events data, and those data are highly reassuring, he added.

MESA is a prospective, population-based cohort study. This analysis included 6,814 subjects aged 45-84 who were free of clinical cardiovascular disease at baseline, when their CAC score was determined. At that time, 3,415 participants had a CAC score of 0 and 508 had a score of 1-10.

During a median 10.3 years of follow-up, 123 cardiovascular events occurred, roughly one-third of which were nonfatal acute MIs and half of which were nonfatal strokes; the remainder were cardiovascular deaths.

The event rate was 2.9/1,000 person-years in subjects with a CAC of 0 and significantly greater at 5.5/1,000 person-years with a score of 1-10. However, since the cardiovascular risk factor profile of the zero CAC group was generally more favorable, Dr. Joshi and coinvestigators carried out a Cox proportional hazards analysis factoring in demographics, standard cardiovascular risk factors, body mass index, C-reactive protein level, and carotid intima media thickness. The adjusted 10-year event risk in the group with a CAC score of 1-10 was 1.9-fold greater than with a CAC of 0.

The highest 10-year event rate was noted in subjects with at least three of the following four risk factors at baseline: hypertension, current smoking, diabetes, and hyperlipidemia. The rate was 6.5/1,000 person-years in such individuals if they had a CAC of 0 and doubled at 13.1/1,000 person-years with a score of 1-10.

In a multivariate Cox analysis, age, smoking, and hypertension proved to be significant predictors of cardiovascular events in the group with a CAC of 0 as well as in those with a CAC of 1-10. But there was one important difference between the two groups: While the hazard ratio for cardiovascular events associated with hypertension versus no hypertension was 2.1 in subjects with a CAC of 0, the presence of hypertension in individuals with a CAC of 1-10 increased their event risk by 10.2-fold, or nearly five times greater than the risk increase associated with hypertension in persons with a CAC of 0, Dr. Joshi observed.

Non–HDL cholesterol level was predictive of cardiovascular risk in subjects with a CAC of 1-10 but not in those with a score of 0.

When actual event rates were compared with those predicted by the atherosclerotic cardiovascular disease (ASCVD) risk estimator introduced in the 2013 AHA/American College of Cardiology cholesterol guidelines, the event rate in subjects with an ASCVD 10-year risk estimate of 7.5%-15% but a CAC of 0 was just 4.4%.

Audience members noted that CAC scores didn’t do a very good job of stratifying stroke risk in MESA. That’s not surprising, since the score reflects coronary but not carotid artery calcium. But it is a limitation of CAC as a predictive tool, especially in light of the fact that strokes accounted for half of all cardiovascular events in the study.

Asked where he and his coinvestigators plan to go from here, Dr. Joshi said a randomized, controlled trial would be ideal, but to date funding isn’t available. However, the observational data from MESA and other studies suggest such a trial may not even be needed.

“Certainly the guidelines do allow for CAC scoring to be used in clinical decision making,” he noted.

The MESA study is funded by the National Heart, Lung, and Blood Institute. Dr. Joshi reported having no financial conflicts.

[email protected]

CHICAGO – Absence of coronary artery calcium upon imaging results in an impressively low cardiovascular event rate over the next 10 years regardless of an individual’s level of standard risk factors, according to prospective data from the MESA study.

In contrast, a coronary artery calcium (CAC) score of 1-10, often described as minimal CAC, nearly doubles the 10-year risk, compared with a baseline CAC score of 0.

Prior to these new 10-year data, many cardiologists considered a CAC score of 1-10 as tantamount to no CAC. Not so, Dr. Parag H. Joshi said at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

“A CAC of 0 is presumably identifying someone without any atherosclerosis. Just the presence of minimal calcium suggests that atherosclerosis is building up. Our data suggest that among individuals with a CAC of 1-10, current smoking, elevated non-HDL cholesterol, and particularly hypertension should be treated aggressively,” said Dr. Joshi, a clinical fellow in cardiovascular diseases and prevention at Johns Hopkins University, Baltimore.

Prior studies totaling more than 50,000 subjects with a CAC score of 0 have shown very low cardiovascular event rates over 4-5 years of follow-up. However, current cardiovascular risk estimates focus on 10-year risk. This new analysis from MESA (Multi-Ethnic Study of Atherosclerosis) is the first study to provide prospective, 10-year events data, and those data are highly reassuring, he added.

MESA is a prospective, population-based cohort study. This analysis included 6,814 subjects aged 45-84 who were free of clinical cardiovascular disease at baseline, when their CAC score was determined. At that time, 3,415 participants had a CAC score of 0 and 508 had a score of 1-10.

During a median 10.3 years of follow-up, 123 cardiovascular events occurred, roughly one-third of which were nonfatal acute MIs and half of which were nonfatal strokes; the remainder were cardiovascular deaths.

The event rate was 2.9/1,000 person-years in subjects with a CAC of 0 and significantly greater at 5.5/1,000 person-years with a score of 1-10. However, since the cardiovascular risk factor profile of the zero CAC group was generally more favorable, Dr. Joshi and coinvestigators carried out a Cox proportional hazards analysis factoring in demographics, standard cardiovascular risk factors, body mass index, C-reactive protein level, and carotid intima media thickness. The adjusted 10-year event risk in the group with a CAC score of 1-10 was 1.9-fold greater than with a CAC of 0.

The highest 10-year event rate was noted in subjects with at least three of the following four risk factors at baseline: hypertension, current smoking, diabetes, and hyperlipidemia. The rate was 6.5/1,000 person-years in such individuals if they had a CAC of 0 and doubled at 13.1/1,000 person-years with a score of 1-10.

In a multivariate Cox analysis, age, smoking, and hypertension proved to be significant predictors of cardiovascular events in the group with a CAC of 0 as well as in those with a CAC of 1-10. But there was one important difference between the two groups: While the hazard ratio for cardiovascular events associated with hypertension versus no hypertension was 2.1 in subjects with a CAC of 0, the presence of hypertension in individuals with a CAC of 1-10 increased their event risk by 10.2-fold, or nearly five times greater than the risk increase associated with hypertension in persons with a CAC of 0, Dr. Joshi observed.

Non–HDL cholesterol level was predictive of cardiovascular risk in subjects with a CAC of 1-10 but not in those with a score of 0.

When actual event rates were compared with those predicted by the atherosclerotic cardiovascular disease (ASCVD) risk estimator introduced in the 2013 AHA/American College of Cardiology cholesterol guidelines, the event rate in subjects with an ASCVD 10-year risk estimate of 7.5%-15% but a CAC of 0 was just 4.4%.

Audience members noted that CAC scores didn’t do a very good job of stratifying stroke risk in MESA. That’s not surprising, since the score reflects coronary but not carotid artery calcium. But it is a limitation of CAC as a predictive tool, especially in light of the fact that strokes accounted for half of all cardiovascular events in the study.

Asked where he and his coinvestigators plan to go from here, Dr. Joshi said a randomized, controlled trial would be ideal, but to date funding isn’t available. However, the observational data from MESA and other studies suggest such a trial may not even be needed.

“Certainly the guidelines do allow for CAC scoring to be used in clinical decision making,” he noted.

The MESA study is funded by the National Heart, Lung, and Blood Institute. Dr. Joshi reported having no financial conflicts.

[email protected]

CHICAGO– Abnormal levels of high-sensitivity cardiac troponin T are present in 40% of type 2 diabetic patients with stable ischemic heart disease, and they do not bode well, according to a new secondary analysis of the BARI 2D study.

In BARI 2D, an abnormal high-sensitivity cardiac troponin T (hsTnT), defined as 14 ng/L or greater, a powerful marker of ongoing myocardial injury, was independently associated with a doubled 5-year risk of the composite endpoint of cardiovascular death, MI, or stroke. Moreover, and discouragingly so, prompt coronary revascularization did nothing to mitigate that risk, Dr. Brendan M. Everett reported at the American Heart Association Scientific Sessions.

Further, early coronary revascularization did not result in a reduction in abnormal hsTnT at 1 year of follow-up, said Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.

“To better address the risk represented by an abnormal hsTnT, we need to gain an improved understanding of the biology of troponin release in this population,” he observed. “The fact that we saw an overall decrease of about 0.5% in hemoglobin A_1c and an LDL reduction of 16 mg/dL at 1 year and still there was no change in hsTnT leaves me scratching my head. The abnormal hsTnT is clearly a marker of badness, but where is it coming from? Can we address it? Or are we just left to look at it and worry about our patients who have an abnormal hsTnT?”

The BARI 2D trial was designed to learn whether patients with type 2 diabetes and stable ischemic heart disease benefit from prompt coronary revascularization plus intensive medical therapy as compared with intensive medical therapy alone. As previously reported (N. Engl. J. Med. 2009;360:2503-15), this proved not to be the case; prompt revascularization conferred no outcome advantage.

The aim of Dr. Everett’s new secondary analysis of BARI 2D was to learn if the hsTnT assay can be used to identify a subgroup of patients with type 2 diabetes and stable ischemic heart disease who might benefit from prompt coronary revascularization. The rationale was that, in patients with acute coronary syndromes, it’s well established that an abnormal hsTnT is associated with poor prognosis, and such patients would benefit from early revascularization.

The secondary analysis included 2,285 type 2 diabetics with stable ischemic heart disease whose physicians first decided whether they were better candidates for percutaneous coronary intervention or CABG surgery. Patients were then randomized to prompt revascularization by the preferred method plus intensive medical therapy or to intensive medical therapy alone.

Forty percent of participants had an abnormal hsTnT at baseline. Their 5-year rate of the composite primary endpoint of cardiovascular death, MI, or stroke was 27.1%, compared with 12.9% in patients with a baseline hsTnT below 14 ng/mL. After adjusting in a multivariate analysis for various potential confounders – including age, race, and the standard cardiovascular risk factors – the group with an abnormal baseline hsTnT had a 2.09-fold increased risk of a major cardiovascular event.

Early revascularization, regardless of whether by percutaneous coronary intervention or coronary artery bypass graft surgery, provided no benefit no matter what the patient’s baseline hsTnT level. In patients with an hsTnT of 14 ng/L or greater, the 5-year rate of the composite outcome was 26.5% with early revascularization compared with 27.6% with intensive medical therapy. In those with an hsTnT below 14 ng/L, the rate was 11.8% in the early revascularization group and 14% with medical management, a trend favoring prompt revascularization that didn’t achieve statistical significance, according to Dr. Everett.

Of patients with an abnormal hsTnT at baseline, 77% still had an abnormal value at 1 year, regardless of whether they underwent prompt revascularization or intensive medical therapy alone.

Session moderator Dr. Mikhail N. Kosiborod commented that the new BARI 2D substudy highlights a dilemma: “We know that a large population of patients with diabetes, and to some extent those with prediabetes, have elevated hsTnT levels, and we know those patients don’t do well. What we don’t know is what to do about it.”

“What [Dr. Everett’s] study clearly demonstrates is that this does not appear to be driven by epicardial coronary artery disease. If we fix the epicardial CAD, it has absolutely no impact on the outcomes nor on the actual troponin level at follow-up. As far as I can tell, it doesn’t appear to be a glycemic control issue, either. It appears that this is a humoral issue. There are ‘evil humors’ – whatever they are – and we don’t really understand what they are or what to do about it,” said Dr. Kosiborod, professor of medicine at the University of Missouri, Kansas City.

“The truth of the matter is we have no idea what’s causing this low-grade myocardial necrosis, and it’s a hugely important thing,” he continued. “There is absolutely no question that elevated hsTnT, even at very low levels, has a huge impact on subsequent risk of heart failure. We know what the public health effects of heart failure are. And patients with diabetes and heart failure tend to do particularly poorly.”

The BARI 2D trial was funded by the National Institutes of Health. Dr. Everett’s secondary analysis was funded by Roche Diagnostics. He reported receiving research grants from Roche and Novartis.

[email protected]

CHICAGO– Abnormal levels of high-sensitivity cardiac troponin T are present in 40% of type 2 diabetic patients with stable ischemic heart disease, and they do not bode well, according to a new secondary analysis of the BARI 2D study.

In BARI 2D, an abnormal high-sensitivity cardiac troponin T (hsTnT), defined as 14 ng/L or greater, a powerful marker of ongoing myocardial injury, was independently associated with a doubled 5-year risk of the composite endpoint of cardiovascular death, MI, or stroke. Moreover, and discouragingly so, prompt coronary revascularization did nothing to mitigate that risk, Dr. Brendan M. Everett reported at the American Heart Association Scientific Sessions.

Further, early coronary revascularization did not result in a reduction in abnormal hsTnT at 1 year of follow-up, said Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.

“To better address the risk represented by an abnormal hsTnT, we need to gain an improved understanding of the biology of troponin release in this population,” he observed. “The fact that we saw an overall decrease of about 0.5% in hemoglobin A_1c and an LDL reduction of 16 mg/dL at 1 year and still there was no change in hsTnT leaves me scratching my head. The abnormal hsTnT is clearly a marker of badness, but where is it coming from? Can we address it? Or are we just left to look at it and worry about our patients who have an abnormal hsTnT?”

The BARI 2D trial was designed to learn whether patients with type 2 diabetes and stable ischemic heart disease benefit from prompt coronary revascularization plus intensive medical therapy as compared with intensive medical therapy alone. As previously reported (N. Engl. J. Med. 2009;360:2503-15), this proved not to be the case; prompt revascularization conferred no outcome advantage.

The aim of Dr. Everett’s new secondary analysis of BARI 2D was to learn if the hsTnT assay can be used to identify a subgroup of patients with type 2 diabetes and stable ischemic heart disease who might benefit from prompt coronary revascularization. The rationale was that, in patients with acute coronary syndromes, it’s well established that an abnormal hsTnT is associated with poor prognosis, and such patients would benefit from early revascularization.

The secondary analysis included 2,285 type 2 diabetics with stable ischemic heart disease whose physicians first decided whether they were better candidates for percutaneous coronary intervention or CABG surgery. Patients were then randomized to prompt revascularization by the preferred method plus intensive medical therapy or to intensive medical therapy alone.

Forty percent of participants had an abnormal hsTnT at baseline. Their 5-year rate of the composite primary endpoint of cardiovascular death, MI, or stroke was 27.1%, compared with 12.9% in patients with a baseline hsTnT below 14 ng/mL. After adjusting in a multivariate analysis for various potential confounders – including age, race, and the standard cardiovascular risk factors – the group with an abnormal baseline hsTnT had a 2.09-fold increased risk of a major cardiovascular event.

Early revascularization, regardless of whether by percutaneous coronary intervention or coronary artery bypass graft surgery, provided no benefit no matter what the patient’s baseline hsTnT level. In patients with an hsTnT of 14 ng/L or greater, the 5-year rate of the composite outcome was 26.5% with early revascularization compared with 27.6% with intensive medical therapy. In those with an hsTnT below 14 ng/L, the rate was 11.8% in the early revascularization group and 14% with medical management, a trend favoring prompt revascularization that didn’t achieve statistical significance, according to Dr. Everett.

Of patients with an abnormal hsTnT at baseline, 77% still had an abnormal value at 1 year, regardless of whether they underwent prompt revascularization or intensive medical therapy alone.

Session moderator Dr. Mikhail N. Kosiborod commented that the new BARI 2D substudy highlights a dilemma: “We know that a large population of patients with diabetes, and to some extent those with prediabetes, have elevated hsTnT levels, and we know those patients don’t do well. What we don’t know is what to do about it.”

“What [Dr. Everett’s] study clearly demonstrates is that this does not appear to be driven by epicardial coronary artery disease. If we fix the epicardial CAD, it has absolutely no impact on the outcomes nor on the actual troponin level at follow-up. As far as I can tell, it doesn’t appear to be a glycemic control issue, either. It appears that this is a humoral issue. There are ‘evil humors’ – whatever they are – and we don’t really understand what they are or what to do about it,” said Dr. Kosiborod, professor of medicine at the University of Missouri, Kansas City.

“The truth of the matter is we have no idea what’s causing this low-grade myocardial necrosis, and it’s a hugely important thing,” he continued. “There is absolutely no question that elevated hsTnT, even at very low levels, has a huge impact on subsequent risk of heart failure. We know what the public health effects of heart failure are. And patients with diabetes and heart failure tend to do particularly poorly.”

The BARI 2D trial was funded by the National Institutes of Health. Dr. Everett’s secondary analysis was funded by Roche Diagnostics. He reported receiving research grants from Roche and Novartis.

[email protected]

CHICAGO– Abnormal levels of high-sensitivity cardiac troponin T are present in 40% of type 2 diabetic patients with stable ischemic heart disease, and they do not bode well, according to a new secondary analysis of the BARI 2D study.

In BARI 2D, an abnormal high-sensitivity cardiac troponin T (hsTnT), defined as 14 ng/L or greater, a powerful marker of ongoing myocardial injury, was independently associated with a doubled 5-year risk of the composite endpoint of cardiovascular death, MI, or stroke. Moreover, and discouragingly so, prompt coronary revascularization did nothing to mitigate that risk, Dr. Brendan M. Everett reported at the American Heart Association Scientific Sessions.

Further, early coronary revascularization did not result in a reduction in abnormal hsTnT at 1 year of follow-up, said Dr. Everett, director of the general cardiology inpatient service at Brigham and Women’s Hospital, Boston.

“To better address the risk represented by an abnormal hsTnT, we need to gain an improved understanding of the biology of troponin release in this population,” he observed. “The fact that we saw an overall decrease of about 0.5% in hemoglobin A_1c and an LDL reduction of 16 mg/dL at 1 year and still there was no change in hsTnT leaves me scratching my head. The abnormal hsTnT is clearly a marker of badness, but where is it coming from? Can we address it? Or are we just left to look at it and worry about our patients who have an abnormal hsTnT?”

The BARI 2D trial was designed to learn whether patients with type 2 diabetes and stable ischemic heart disease benefit from prompt coronary revascularization plus intensive medical therapy as compared with intensive medical therapy alone. As previously reported (N. Engl. J. Med. 2009;360:2503-15), this proved not to be the case; prompt revascularization conferred no outcome advantage.

The aim of Dr. Everett’s new secondary analysis of BARI 2D was to learn if the hsTnT assay can be used to identify a subgroup of patients with type 2 diabetes and stable ischemic heart disease who might benefit from prompt coronary revascularization. The rationale was that, in patients with acute coronary syndromes, it’s well established that an abnormal hsTnT is associated with poor prognosis, and such patients would benefit from early revascularization.

The secondary analysis included 2,285 type 2 diabetics with stable ischemic heart disease whose physicians first decided whether they were better candidates for percutaneous coronary intervention or CABG surgery. Patients were then randomized to prompt revascularization by the preferred method plus intensive medical therapy or to intensive medical therapy alone.

Forty percent of participants had an abnormal hsTnT at baseline. Their 5-year rate of the composite primary endpoint of cardiovascular death, MI, or stroke was 27.1%, compared with 12.9% in patients with a baseline hsTnT below 14 ng/mL. After adjusting in a multivariate analysis for various potential confounders – including age, race, and the standard cardiovascular risk factors – the group with an abnormal baseline hsTnT had a 2.09-fold increased risk of a major cardiovascular event.

Early revascularization, regardless of whether by percutaneous coronary intervention or coronary artery bypass graft surgery, provided no benefit no matter what the patient’s baseline hsTnT level. In patients with an hsTnT of 14 ng/L or greater, the 5-year rate of the composite outcome was 26.5% with early revascularization compared with 27.6% with intensive medical therapy. In those with an hsTnT below 14 ng/L, the rate was 11.8% in the early revascularization group and 14% with medical management, a trend favoring prompt revascularization that didn’t achieve statistical significance, according to Dr. Everett.

Of patients with an abnormal hsTnT at baseline, 77% still had an abnormal value at 1 year, regardless of whether they underwent prompt revascularization or intensive medical therapy alone.

Session moderator Dr. Mikhail N. Kosiborod commented that the new BARI 2D substudy highlights a dilemma: “We know that a large population of patients with diabetes, and to some extent those with prediabetes, have elevated hsTnT levels, and we know those patients don’t do well. What we don’t know is what to do about it.”

“What [Dr. Everett’s] study clearly demonstrates is that this does not appear to be driven by epicardial coronary artery disease. If we fix the epicardial CAD, it has absolutely no impact on the outcomes nor on the actual troponin level at follow-up. As far as I can tell, it doesn’t appear to be a glycemic control issue, either. It appears that this is a humoral issue. There are ‘evil humors’ – whatever they are – and we don’t really understand what they are or what to do about it,” said Dr. Kosiborod, professor of medicine at the University of Missouri, Kansas City.

“The truth of the matter is we have no idea what’s causing this low-grade myocardial necrosis, and it’s a hugely important thing,” he continued. “There is absolutely no question that elevated hsTnT, even at very low levels, has a huge impact on subsequent risk of heart failure. We know what the public health effects of heart failure are. And patients with diabetes and heart failure tend to do particularly poorly.”

The BARI 2D trial was funded by the National Institutes of Health. Dr. Everett’s secondary analysis was funded by Roche Diagnostics. He reported receiving research grants from Roche and Novartis.

[email protected]

CHICAGO – Early results from a randomized trial cast doubt on the benefits of routinely repairing a leaky mitral valve during coronary artery bypass grafting in patients with moderate ischemic mitral regurgitation.

At 1 year, there was no significant difference between patients undergoing CABG alone or CABG plus mitral repair in the primary endpoint of left ventricular reverse modeling, as defined by changes in LV end-systolic volume index (LVESVI) at 1 year (z score 0.50).

Both groups achieved significant reductions in LVESVI, with a median reduction of about 6 mL/m² from baseline, Dr. Robert Michler, chair of cardiovascular and thoracic surgery at Montefiore Medical Center, New York, reported at the American Heart Association scientific sessions.

At 1 year, patients who underwent CABG and mitral valve repair had significantly less residual moderate or severe mitral regurgitation (11% vs. 31%; P < .001).

On the other hand, the combination procedure was associated with significantly higher rates of any neurologic event (9.6% vs. 3.1%; P = .03), longer cross-clamp (117 vs. 74 minutes) and cardiopulmonary bypass times (163 vs. 106 minutes; P values both < .001), and longer ICU (4.8 vs. 4.0 days; P = .006) and hospital length of stay (11.3 vs. 9.4 days; P = .002), according to the results, also published online (N. Engl. J. Med. 2014 [doi: 10.1056/NEJMoa1410490]).

“The trial did not demonstrate a clinically meaningful advantage to the routine addition of mitral valve repair to CABG,” Dr. Michler said, on behalf of the Cardiothoracic Surgical Trials Network investigators.

The 2014 AHA/American College of Cardiology mitral valve guidelines give a weak class IIb recommendation for mitral valve repair for patients with chronic mitral regurgitation (MR) who are undergoing other cardiac surgery, he noted.

The study evenly randomized 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus valve repair with an undersized ring (average, 28.3 mm for men and 27.1 mm for women).

The mean LVESVI at baseline was 54.8 mL/m² in the CABG-alone group and 59.6 mL/m² in the combined procedure group.

At 12 months, mean LVESVIs were 46.1 mL/m² and 49.6 mL/m², respectively.

The trial lacked a clinical primary endpoint, and longer follow-up is ongoing to determine whether the lower incidence of moderate or severe MR at 1 year will translate into a net clinical benefit for patients undergoing CABG plus mitral repair, Dr. Michler said.

Designated discussant Dr. David Adams, director of Mount Sinai Hospital’s mitral valve repair reference center in New York, cautioned the audience on the length of the study and called for a full 5 years of follow-up rather than the 2 years as planned.

“Ischemic mitral regurgitation is a disease that hurts you over time. That’s in patients that have had MI, had previous CABG, had attempted mitral valve repair, and had PCI [percutaneous coronary intervention]. So we need much longer term follow-up of this very important data set to really understand its implications,” he said.

In light of roughly half of the patients being in heart failure at baseline, session cochair Dr. Robert Bonow, vice chair of medicine, Northwestern University, Chicago, questioned whether there were differences in outcomes related to changes in baseline ejection fraction (EF) or whether improvement in EF in patients with low EF correlated with reduction in mitral regurgitation with CABG alone.

What is known right now is that mean LVEF increased to the same degree after CABG in both groups, Dr. Michler responded. This was true despite this being a “sick population of patients,” with more than half having diabetes, 50% with heart failure, 20% with renal insufficiency, 10% with prior stroke, and a mean ejection fraction of 40% in both groups.

“What we have yet to identify and plan to explore is the correlation between reverse ventricular remodeling, ejection fraction, and outcome, meaning both the degree of mitral regurgitation and whether there is any signal with respect to repeat hospitalizations, heart failure, or possibly even mortality,” Dr. Michler said.

Both Dr. Michler and Dr. Adams remarked that surgery was extremely safe for the CABG alone and CABG plus MR groups, as reflected by the low mortality at 30 days (2.7% vs. 1.3%) and 1 year (7.3% vs. 6.7%).

The composite endpoint of major adverse cardiac or cerebrovascular events was also similar between groups.

The trial was funded by the National Institutes of Health and the Canadian Institutes for Health Research. Dr. Michler reported grant support from NIH during the conduct of the study. Dr. Adams reported coinventing a mitral valve repair ring.

[email protected]

CHICAGO – Early results from a randomized trial cast doubt on the benefits of routinely repairing a leaky mitral valve during coronary artery bypass grafting in patients with moderate ischemic mitral regurgitation.

At 1 year, there was no significant difference between patients undergoing CABG alone or CABG plus mitral repair in the primary endpoint of left ventricular reverse modeling, as defined by changes in LV end-systolic volume index (LVESVI) at 1 year (z score 0.50).

Both groups achieved significant reductions in LVESVI, with a median reduction of about 6 mL/m² from baseline, Dr. Robert Michler, chair of cardiovascular and thoracic surgery at Montefiore Medical Center, New York, reported at the American Heart Association scientific sessions.

At 1 year, patients who underwent CABG and mitral valve repair had significantly less residual moderate or severe mitral regurgitation (11% vs. 31%; P < .001).

On the other hand, the combination procedure was associated with significantly higher rates of any neurologic event (9.6% vs. 3.1%; P = .03), longer cross-clamp (117 vs. 74 minutes) and cardiopulmonary bypass times (163 vs. 106 minutes; P values both < .001), and longer ICU (4.8 vs. 4.0 days; P = .006) and hospital length of stay (11.3 vs. 9.4 days; P = .002), according to the results, also published online (N. Engl. J. Med. 2014 [doi: 10.1056/NEJMoa1410490]).

“The trial did not demonstrate a clinically meaningful advantage to the routine addition of mitral valve repair to CABG,” Dr. Michler said, on behalf of the Cardiothoracic Surgical Trials Network investigators.

The 2014 AHA/American College of Cardiology mitral valve guidelines give a weak class IIb recommendation for mitral valve repair for patients with chronic mitral regurgitation (MR) who are undergoing other cardiac surgery, he noted.

The study evenly randomized 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus valve repair with an undersized ring (average, 28.3 mm for men and 27.1 mm for women).

The mean LVESVI at baseline was 54.8 mL/m² in the CABG-alone group and 59.6 mL/m² in the combined procedure group.

At 12 months, mean LVESVIs were 46.1 mL/m² and 49.6 mL/m², respectively.

The trial lacked a clinical primary endpoint, and longer follow-up is ongoing to determine whether the lower incidence of moderate or severe MR at 1 year will translate into a net clinical benefit for patients undergoing CABG plus mitral repair, Dr. Michler said.

Designated discussant Dr. David Adams, director of Mount Sinai Hospital’s mitral valve repair reference center in New York, cautioned the audience on the length of the study and called for a full 5 years of follow-up rather than the 2 years as planned.

“Ischemic mitral regurgitation is a disease that hurts you over time. That’s in patients that have had MI, had previous CABG, had attempted mitral valve repair, and had PCI [percutaneous coronary intervention]. So we need much longer term follow-up of this very important data set to really understand its implications,” he said.

In light of roughly half of the patients being in heart failure at baseline, session cochair Dr. Robert Bonow, vice chair of medicine, Northwestern University, Chicago, questioned whether there were differences in outcomes related to changes in baseline ejection fraction (EF) or whether improvement in EF in patients with low EF correlated with reduction in mitral regurgitation with CABG alone.

What is known right now is that mean LVEF increased to the same degree after CABG in both groups, Dr. Michler responded. This was true despite this being a “sick population of patients,” with more than half having diabetes, 50% with heart failure, 20% with renal insufficiency, 10% with prior stroke, and a mean ejection fraction of 40% in both groups.

“What we have yet to identify and plan to explore is the correlation between reverse ventricular remodeling, ejection fraction, and outcome, meaning both the degree of mitral regurgitation and whether there is any signal with respect to repeat hospitalizations, heart failure, or possibly even mortality,” Dr. Michler said.

Both Dr. Michler and Dr. Adams remarked that surgery was extremely safe for the CABG alone and CABG plus MR groups, as reflected by the low mortality at 30 days (2.7% vs. 1.3%) and 1 year (7.3% vs. 6.7%).

The composite endpoint of major adverse cardiac or cerebrovascular events was also similar between groups.

The trial was funded by the National Institutes of Health and the Canadian Institutes for Health Research. Dr. Michler reported grant support from NIH during the conduct of the study. Dr. Adams reported coinventing a mitral valve repair ring.

[email protected]

CHICAGO – Early results from a randomized trial cast doubt on the benefits of routinely repairing a leaky mitral valve during coronary artery bypass grafting in patients with moderate ischemic mitral regurgitation.

At 1 year, there was no significant difference between patients undergoing CABG alone or CABG plus mitral repair in the primary endpoint of left ventricular reverse modeling, as defined by changes in LV end-systolic volume index (LVESVI) at 1 year (z score 0.50).

Both groups achieved significant reductions in LVESVI, with a median reduction of about 6 mL/m² from baseline, Dr. Robert Michler, chair of cardiovascular and thoracic surgery at Montefiore Medical Center, New York, reported at the American Heart Association scientific sessions.

At 1 year, patients who underwent CABG and mitral valve repair had significantly less residual moderate or severe mitral regurgitation (11% vs. 31%; P < .001).

On the other hand, the combination procedure was associated with significantly higher rates of any neurologic event (9.6% vs. 3.1%; P = .03), longer cross-clamp (117 vs. 74 minutes) and cardiopulmonary bypass times (163 vs. 106 minutes; P values both < .001), and longer ICU (4.8 vs. 4.0 days; P = .006) and hospital length of stay (11.3 vs. 9.4 days; P = .002), according to the results, also published online (N. Engl. J. Med. 2014 [doi: 10.1056/NEJMoa1410490]).

“The trial did not demonstrate a clinically meaningful advantage to the routine addition of mitral valve repair to CABG,” Dr. Michler said, on behalf of the Cardiothoracic Surgical Trials Network investigators.

The 2014 AHA/American College of Cardiology mitral valve guidelines give a weak class IIb recommendation for mitral valve repair for patients with chronic mitral regurgitation (MR) who are undergoing other cardiac surgery, he noted.

The study evenly randomized 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus valve repair with an undersized ring (average, 28.3 mm for men and 27.1 mm for women).

The mean LVESVI at baseline was 54.8 mL/m² in the CABG-alone group and 59.6 mL/m² in the combined procedure group.

At 12 months, mean LVESVIs were 46.1 mL/m² and 49.6 mL/m², respectively.

The trial lacked a clinical primary endpoint, and longer follow-up is ongoing to determine whether the lower incidence of moderate or severe MR at 1 year will translate into a net clinical benefit for patients undergoing CABG plus mitral repair, Dr. Michler said.

Designated discussant Dr. David Adams, director of Mount Sinai Hospital’s mitral valve repair reference center in New York, cautioned the audience on the length of the study and called for a full 5 years of follow-up rather than the 2 years as planned.

“Ischemic mitral regurgitation is a disease that hurts you over time. That’s in patients that have had MI, had previous CABG, had attempted mitral valve repair, and had PCI [percutaneous coronary intervention]. So we need much longer term follow-up of this very important data set to really understand its implications,” he said.

In light of roughly half of the patients being in heart failure at baseline, session cochair Dr. Robert Bonow, vice chair of medicine, Northwestern University, Chicago, questioned whether there were differences in outcomes related to changes in baseline ejection fraction (EF) or whether improvement in EF in patients with low EF correlated with reduction in mitral regurgitation with CABG alone.

What is known right now is that mean LVEF increased to the same degree after CABG in both groups, Dr. Michler responded. This was true despite this being a “sick population of patients,” with more than half having diabetes, 50% with heart failure, 20% with renal insufficiency, 10% with prior stroke, and a mean ejection fraction of 40% in both groups.

“What we have yet to identify and plan to explore is the correlation between reverse ventricular remodeling, ejection fraction, and outcome, meaning both the degree of mitral regurgitation and whether there is any signal with respect to repeat hospitalizations, heart failure, or possibly even mortality,” Dr. Michler said.

Both Dr. Michler and Dr. Adams remarked that surgery was extremely safe for the CABG alone and CABG plus MR groups, as reflected by the low mortality at 30 days (2.7% vs. 1.3%) and 1 year (7.3% vs. 6.7%).

The composite endpoint of major adverse cardiac or cerebrovascular events was also similar between groups.

The trial was funded by the National Institutes of Health and the Canadian Institutes for Health Research. Dr. Michler reported grant support from NIH during the conduct of the study. Dr. Adams reported coinventing a mitral valve repair ring.

[email protected]

VIENNA – Routine use of CT or three-dimensional echocardiography before and during transcatheter aortic valve replacement has contributed to a dramatic drop in paravalvular leaks, the procedure’s Achilles heel, based on the experience at a single, high-volume U.S. center.

In recent months, during testing of the SAPIEN 3 transcatheter aortic valve replacement (TAVR) system under development by Edwards, no patients developed moderate or severe paravalvular regurgitation during follow-up, and mild paravalvular leaks occurred at a rate of 7%-9%, Dr. Rebecca T. Hahn said at the annual meeting of the European Association of Cardiovascular Imaging. She and her associates tallied these rates recently at their institution, Columbia University Medical Center in New York, during their participation in PARTNER II, a multicenter study of the SAPIEN 3 device.

Dr. Hahn attributed these unprecedentedly low rates to three factors: preprocedure imaging with CT or 3-D echocardiography to select the best-sized valve for each patient, routine use of intraprocedural 3-D echo to guide precise valve placement and monitor for complications, and the SAPIEN 3 valve.

To put these regurgitation rates in context, in results from the pivotal CoreValve trial reported last May, the 30-day rate of moderate or severe paravalvular regurgitation was 9%, and the rate of mild paravalvular regurgitation was 36% (N. Engl. J. Med. 2014;370:1790-8). The most recent data on paravalvular leak reported from a large trial using a SAPIEN valve currently on the U.S. market was from the PARTNER II trial of inoperable patients, which documented a roughly 20% rate of moderate or severe paravalvular regurgitation using either the SAPIEN XT or the original SAPIEN system.

Dr. Hahn acknowledged that one major factor contributing to the disappearance of moderate or severe leaks following TAVR was the design of the new SAPIEN 3 TAVR valve she is working with, which features a flexible layer around the outer perimeter of the valve to better seal it into the patient’s aortic valve annulus and prevent blood from leaking through gaps around the edge.

But she also credited intraprocedural 3-D echo as a major factor in the improved outcomes, as well as the use of CT or 3-D echo to accurately size the annulus before TAVR starts so that the patient’s annulus size can be matched with the most appropriately sized replacement valve.

“Each valve has a sweet spot” for the annulus size it will fit into, and CT imaging of the annulus to measure the size, or using three-dimensional echo when CT is not good enough, is the way that TAVR heart teams now make sure they use the valve size with a sweet spot for the patient receiving the valve, said Dr. Hahn, director of invasive and valvular echocardiography at Columbia. A key task for either imaging method is to measure annulus size on the “virtual” annular plane, a plane that is challenging to identify as it is defined by only the three hinge points of the aortic valve’s leaflets. “Three-dimensional echo allows us to quantify [annular size] in ways that we couldn’t before,” she said in an interview.

During the procedure, 3-D echocardiography is the only good imaging option. In addition to clarifying unusual morphologies of the annulus and surrounding tissues and blood vessels, and giving precise information on wire and valve placement, 3-D echo allows for rapid assessment of a hemodynamic emergency if one occurs during a TAVR procedure. Three-dimensional echo also affords the best way to assess the location and severity of paravalvular regurgitation. 3-D echo “allows us to make decisions during the procedure on what to do about paravalvular regurgitation,” Dr. Hahn said.

[email protected]

On Twitter @mitchelzoler

VIENNA – Routine use of CT or three-dimensional echocardiography before and during transcatheter aortic valve replacement has contributed to a dramatic drop in paravalvular leaks, the procedure’s Achilles heel, based on the experience at a single, high-volume U.S. center.

In recent months, during testing of the SAPIEN 3 transcatheter aortic valve replacement (TAVR) system under development by Edwards, no patients developed moderate or severe paravalvular regurgitation during follow-up, and mild paravalvular leaks occurred at a rate of 7%-9%, Dr. Rebecca T. Hahn said at the annual meeting of the European Association of Cardiovascular Imaging. She and her associates tallied these rates recently at their institution, Columbia University Medical Center in New York, during their participation in PARTNER II, a multicenter study of the SAPIEN 3 device.

Dr. Hahn attributed these unprecedentedly low rates to three factors: preprocedure imaging with CT or 3-D echocardiography to select the best-sized valve for each patient, routine use of intraprocedural 3-D echo to guide precise valve placement and monitor for complications, and the SAPIEN 3 valve.

To put these regurgitation rates in context, in results from the pivotal CoreValve trial reported last May, the 30-day rate of moderate or severe paravalvular regurgitation was 9%, and the rate of mild paravalvular regurgitation was 36% (N. Engl. J. Med. 2014;370:1790-8). The most recent data on paravalvular leak reported from a large trial using a SAPIEN valve currently on the U.S. market was from the PARTNER II trial of inoperable patients, which documented a roughly 20% rate of moderate or severe paravalvular regurgitation using either the SAPIEN XT or the original SAPIEN system.

Dr. Hahn acknowledged that one major factor contributing to the disappearance of moderate or severe leaks following TAVR was the design of the new SAPIEN 3 TAVR valve she is working with, which features a flexible layer around the outer perimeter of the valve to better seal it into the patient’s aortic valve annulus and prevent blood from leaking through gaps around the edge.

But she also credited intraprocedural 3-D echo as a major factor in the improved outcomes, as well as the use of CT or 3-D echo to accurately size the annulus before TAVR starts so that the patient’s annulus size can be matched with the most appropriately sized replacement valve.

“Each valve has a sweet spot” for the annulus size it will fit into, and CT imaging of the annulus to measure the size, or using three-dimensional echo when CT is not good enough, is the way that TAVR heart teams now make sure they use the valve size with a sweet spot for the patient receiving the valve, said Dr. Hahn, director of invasive and valvular echocardiography at Columbia. A key task for either imaging method is to measure annulus size on the “virtual” annular plane, a plane that is challenging to identify as it is defined by only the three hinge points of the aortic valve’s leaflets. “Three-dimensional echo allows us to quantify [annular size] in ways that we couldn’t before,” she said in an interview.

During the procedure, 3-D echocardiography is the only good imaging option. In addition to clarifying unusual morphologies of the annulus and surrounding tissues and blood vessels, and giving precise information on wire and valve placement, 3-D echo allows for rapid assessment of a hemodynamic emergency if one occurs during a TAVR procedure. Three-dimensional echo also affords the best way to assess the location and severity of paravalvular regurgitation. 3-D echo “allows us to make decisions during the procedure on what to do about paravalvular regurgitation,” Dr. Hahn said.

[email protected]

On Twitter @mitchelzoler

VIENNA – Routine use of CT or three-dimensional echocardiography before and during transcatheter aortic valve replacement has contributed to a dramatic drop in paravalvular leaks, the procedure’s Achilles heel, based on the experience at a single, high-volume U.S. center.

In recent months, during testing of the SAPIEN 3 transcatheter aortic valve replacement (TAVR) system under development by Edwards, no patients developed moderate or severe paravalvular regurgitation during follow-up, and mild paravalvular leaks occurred at a rate of 7%-9%, Dr. Rebecca T. Hahn said at the annual meeting of the European Association of Cardiovascular Imaging. She and her associates tallied these rates recently at their institution, Columbia University Medical Center in New York, during their participation in PARTNER II, a multicenter study of the SAPIEN 3 device.

Dr. Hahn attributed these unprecedentedly low rates to three factors: preprocedure imaging with CT or 3-D echocardiography to select the best-sized valve for each patient, routine use of intraprocedural 3-D echo to guide precise valve placement and monitor for complications, and the SAPIEN 3 valve.

To put these regurgitation rates in context, in results from the pivotal CoreValve trial reported last May, the 30-day rate of moderate or severe paravalvular regurgitation was 9%, and the rate of mild paravalvular regurgitation was 36% (N. Engl. J. Med. 2014;370:1790-8). The most recent data on paravalvular leak reported from a large trial using a SAPIEN valve currently on the U.S. market was from the PARTNER II trial of inoperable patients, which documented a roughly 20% rate of moderate or severe paravalvular regurgitation using either the SAPIEN XT or the original SAPIEN system.

Dr. Hahn acknowledged that one major factor contributing to the disappearance of moderate or severe leaks following TAVR was the design of the new SAPIEN 3 TAVR valve she is working with, which features a flexible layer around the outer perimeter of the valve to better seal it into the patient’s aortic valve annulus and prevent blood from leaking through gaps around the edge.

But she also credited intraprocedural 3-D echo as a major factor in the improved outcomes, as well as the use of CT or 3-D echo to accurately size the annulus before TAVR starts so that the patient’s annulus size can be matched with the most appropriately sized replacement valve.

“Each valve has a sweet spot” for the annulus size it will fit into, and CT imaging of the annulus to measure the size, or using three-dimensional echo when CT is not good enough, is the way that TAVR heart teams now make sure they use the valve size with a sweet spot for the patient receiving the valve, said Dr. Hahn, director of invasive and valvular echocardiography at Columbia. A key task for either imaging method is to measure annulus size on the “virtual” annular plane, a plane that is challenging to identify as it is defined by only the three hinge points of the aortic valve’s leaflets. “Three-dimensional echo allows us to quantify [annular size] in ways that we couldn’t before,” she said in an interview.

During the procedure, 3-D echocardiography is the only good imaging option. In addition to clarifying unusual morphologies of the annulus and surrounding tissues and blood vessels, and giving precise information on wire and valve placement, 3-D echo allows for rapid assessment of a hemodynamic emergency if one occurs during a TAVR procedure. Three-dimensional echo also affords the best way to assess the location and severity of paravalvular regurgitation. 3-D echo “allows us to make decisions during the procedure on what to do about paravalvular regurgitation,” Dr. Hahn said.

[email protected]

On Twitter @mitchelzoler

CHICAGO– Daily low-dose aspirin did not prevent atherosclerotic events in high-risk, elderly Japanese patients in the Japanese Primary Prevention Project.

After a median follow-up of 5 years, the composite primary outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction occurred in 2.77% of patients with hypertension, dyslipidemia, or diabetes on aspirin and 2.96% of those not on aspirin, a nonsignificant difference.

Subgroup analyses did not identify significant differences between study groups, Dr. Kazuyuki Shimada reported at the American Heart Association scientific sessions.The study was stopped prematurely because the number of primary events was insufficient for the study to reach statistical power.

Daily low-dose aspirin, compared with no aspirin, however, significantly reduced the rate of nonfatal myocardial infarction (0.30% vs. 0.58%; HR, 0.53; P = .02) and transient ischemic attack (0.26% vs. 0.49%; HR, 0.57; P = .04).

However, these benefits must be weighed against an 85% increased risk of serious extracranial hemorrhage in patients on daily aspirin (0.86% vs. 0.51%; HR, 1.85, P = .004), Dr. Shimada of Shin-Oyama City Hospital, Tochigi, Japan, said.

Prespecified gastrointestinal adverse events, including stomach/abdominal pain, gastroduodenal ulcer, reflux esophagitis, and gastrointestinal hemorrhage, were also increased in patients on aspirin, according to results of the late-breaking study, simultaneously published online in JAMA (doi:10.1001/jama.2014.15690).

Invited discussant Dr. Dorairaj Prabhakaran of the Public Health Foundation of India in Delhi said the negative results do not spell the “end of the road” for aspirin in primary prevention, but emphasize the need to use an individualized, stepwise risk-benefit approach to aspirin therapy.

“The benefit is very unlikely in very low-risk populations such as those with less than 1% [cardiovascular] events per year,” he said. “There would be a role in special groups such as younger populations, lower-income countries, but these are not evaluated well.”

During the discussion following the study presentation, panelists raised concerns about the development of polypills, most of which are for secondary prevention but typically contain aspirin. Other panelists said the study provides a sobering reminder of the risks faced by patients who put themselves on a daily aspirin regimen without consulting a physician.

The Japanese Primary Prevention Project (JPPP) evenly randomized 14,658 patients, aged at least 60 years, with hypertension, dyslipidemia, or diabetes to enteric aspirin 100 mg or no aspirin. A total of 194 patients were excluded because of protocol violations, study withdrawal, or failing to meet inclusion criteria, leaving 7,220 patients in the aspirin group and 7,244 in the no-aspirin group for the modified intention-to-treat population.

In addition to the lower-than-expected total event rate in both the aspirin and no-aspirin groups (193 vs. 207), the use of statins in both arms could have contributed to the negative results, Dr. Shimada reported. Aspirin adherence also fell from 89% in year 1 to only 76% in year 5, while aspirin use in the no-aspirin group increased from 1.5% to 9.8%.

Further analyses are planned to determine whether aspirin is beneficial in select subgroups or in the prevention of cancer.

Dr. J. Michael Gaziano of Brigham and Women’s Hospital in Boston commented in an accompanying JAMA editorial (doi:10.1001/jama.2014.16047) that information from three ongoing primary prevention aspirin trials in patients at higher-than-average risk “will prove helpful for clinical decision making involving the role of aspirin for primary prevention.”

Those trials include the ASCEND study of aspirin 100 mg with or without omega-3 fatty acids in patients at least 40 years old with diabetes, the ARRIVE trial in middle-aged and older patients at moderate risk of cardiovascular disease, and the ASPREE study in the elderly older than 65 years.

JPPP was sponsored by the Japanese Ministry of Health, Labor, and Welfare, and the Waksman Foundation of Japan. Bayer Yakuhin provided the aspirin. Dr. Shimada reported honorarium from MSD, Shionogi, Takeda, Daiichi-Sankyo, and Dainihon-Sumitomo, and serving as a consultant/advisory board member for Omron. Dr. Prabhakaran reported no relevant financial disclosures. Dr. Gaziano reported serving on the executive committee of the ARRIVE trial and as a consultant for and receiving speaking honoraria from Bayer.

[email protected]

CHICAGO– Daily low-dose aspirin did not prevent atherosclerotic events in high-risk, elderly Japanese patients in the Japanese Primary Prevention Project.

After a median follow-up of 5 years, the composite primary outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction occurred in 2.77% of patients with hypertension, dyslipidemia, or diabetes on aspirin and 2.96% of those not on aspirin, a nonsignificant difference.

Subgroup analyses did not identify significant differences between study groups, Dr. Kazuyuki Shimada reported at the American Heart Association scientific sessions.The study was stopped prematurely because the number of primary events was insufficient for the study to reach statistical power.

Daily low-dose aspirin, compared with no aspirin, however, significantly reduced the rate of nonfatal myocardial infarction (0.30% vs. 0.58%; HR, 0.53; P = .02) and transient ischemic attack (0.26% vs. 0.49%; HR, 0.57; P = .04).

However, these benefits must be weighed against an 85% increased risk of serious extracranial hemorrhage in patients on daily aspirin (0.86% vs. 0.51%; HR, 1.85, P = .004), Dr. Shimada of Shin-Oyama City Hospital, Tochigi, Japan, said.

Prespecified gastrointestinal adverse events, including stomach/abdominal pain, gastroduodenal ulcer, reflux esophagitis, and gastrointestinal hemorrhage, were also increased in patients on aspirin, according to results of the late-breaking study, simultaneously published online in JAMA (doi:10.1001/jama.2014.15690).

Invited discussant Dr. Dorairaj Prabhakaran of the Public Health Foundation of India in Delhi said the negative results do not spell the “end of the road” for aspirin in primary prevention, but emphasize the need to use an individualized, stepwise risk-benefit approach to aspirin therapy.

“The benefit is very unlikely in very low-risk populations such as those with less than 1% [cardiovascular] events per year,” he said. “There would be a role in special groups such as younger populations, lower-income countries, but these are not evaluated well.”

During the discussion following the study presentation, panelists raised concerns about the development of polypills, most of which are for secondary prevention but typically contain aspirin. Other panelists said the study provides a sobering reminder of the risks faced by patients who put themselves on a daily aspirin regimen without consulting a physician.

The Japanese Primary Prevention Project (JPPP) evenly randomized 14,658 patients, aged at least 60 years, with hypertension, dyslipidemia, or diabetes to enteric aspirin 100 mg or no aspirin. A total of 194 patients were excluded because of protocol violations, study withdrawal, or failing to meet inclusion criteria, leaving 7,220 patients in the aspirin group and 7,244 in the no-aspirin group for the modified intention-to-treat population.

In addition to the lower-than-expected total event rate in both the aspirin and no-aspirin groups (193 vs. 207), the use of statins in both arms could have contributed to the negative results, Dr. Shimada reported. Aspirin adherence also fell from 89% in year 1 to only 76% in year 5, while aspirin use in the no-aspirin group increased from 1.5% to 9.8%.

Further analyses are planned to determine whether aspirin is beneficial in select subgroups or in the prevention of cancer.

Dr. J. Michael Gaziano of Brigham and Women’s Hospital in Boston commented in an accompanying JAMA editorial (doi:10.1001/jama.2014.16047) that information from three ongoing primary prevention aspirin trials in patients at higher-than-average risk “will prove helpful for clinical decision making involving the role of aspirin for primary prevention.”

Those trials include the ASCEND study of aspirin 100 mg with or without omega-3 fatty acids in patients at least 40 years old with diabetes, the ARRIVE trial in middle-aged and older patients at moderate risk of cardiovascular disease, and the ASPREE study in the elderly older than 65 years.

JPPP was sponsored by the Japanese Ministry of Health, Labor, and Welfare, and the Waksman Foundation of Japan. Bayer Yakuhin provided the aspirin. Dr. Shimada reported honorarium from MSD, Shionogi, Takeda, Daiichi-Sankyo, and Dainihon-Sumitomo, and serving as a consultant/advisory board member for Omron. Dr. Prabhakaran reported no relevant financial disclosures. Dr. Gaziano reported serving on the executive committee of the ARRIVE trial and as a consultant for and receiving speaking honoraria from Bayer.

[email protected]

CHICAGO– Daily low-dose aspirin did not prevent atherosclerotic events in high-risk, elderly Japanese patients in the Japanese Primary Prevention Project.

After a median follow-up of 5 years, the composite primary outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction occurred in 2.77% of patients with hypertension, dyslipidemia, or diabetes on aspirin and 2.96% of those not on aspirin, a nonsignificant difference.

Subgroup analyses did not identify significant differences between study groups, Dr. Kazuyuki Shimada reported at the American Heart Association scientific sessions.The study was stopped prematurely because the number of primary events was insufficient for the study to reach statistical power.

Daily low-dose aspirin, compared with no aspirin, however, significantly reduced the rate of nonfatal myocardial infarction (0.30% vs. 0.58%; HR, 0.53; P = .02) and transient ischemic attack (0.26% vs. 0.49%; HR, 0.57; P = .04).

However, these benefits must be weighed against an 85% increased risk of serious extracranial hemorrhage in patients on daily aspirin (0.86% vs. 0.51%; HR, 1.85, P = .004), Dr. Shimada of Shin-Oyama City Hospital, Tochigi, Japan, said.

Prespecified gastrointestinal adverse events, including stomach/abdominal pain, gastroduodenal ulcer, reflux esophagitis, and gastrointestinal hemorrhage, were also increased in patients on aspirin, according to results of the late-breaking study, simultaneously published online in JAMA (doi:10.1001/jama.2014.15690).

Invited discussant Dr. Dorairaj Prabhakaran of the Public Health Foundation of India in Delhi said the negative results do not spell the “end of the road” for aspirin in primary prevention, but emphasize the need to use an individualized, stepwise risk-benefit approach to aspirin therapy.

“The benefit is very unlikely in very low-risk populations such as those with less than 1% [cardiovascular] events per year,” he said. “There would be a role in special groups such as younger populations, lower-income countries, but these are not evaluated well.”

During the discussion following the study presentation, panelists raised concerns about the development of polypills, most of which are for secondary prevention but typically contain aspirin. Other panelists said the study provides a sobering reminder of the risks faced by patients who put themselves on a daily aspirin regimen without consulting a physician.

The Japanese Primary Prevention Project (JPPP) evenly randomized 14,658 patients, aged at least 60 years, with hypertension, dyslipidemia, or diabetes to enteric aspirin 100 mg or no aspirin. A total of 194 patients were excluded because of protocol violations, study withdrawal, or failing to meet inclusion criteria, leaving 7,220 patients in the aspirin group and 7,244 in the no-aspirin group for the modified intention-to-treat population.

In addition to the lower-than-expected total event rate in both the aspirin and no-aspirin groups (193 vs. 207), the use of statins in both arms could have contributed to the negative results, Dr. Shimada reported. Aspirin adherence also fell from 89% in year 1 to only 76% in year 5, while aspirin use in the no-aspirin group increased from 1.5% to 9.8%.

Further analyses are planned to determine whether aspirin is beneficial in select subgroups or in the prevention of cancer.

Dr. J. Michael Gaziano of Brigham and Women’s Hospital in Boston commented in an accompanying JAMA editorial (doi:10.1001/jama.2014.16047) that information from three ongoing primary prevention aspirin trials in patients at higher-than-average risk “will prove helpful for clinical decision making involving the role of aspirin for primary prevention.”

Those trials include the ASCEND study of aspirin 100 mg with or without omega-3 fatty acids in patients at least 40 years old with diabetes, the ARRIVE trial in middle-aged and older patients at moderate risk of cardiovascular disease, and the ASPREE study in the elderly older than 65 years.

JPPP was sponsored by the Japanese Ministry of Health, Labor, and Welfare, and the Waksman Foundation of Japan. Bayer Yakuhin provided the aspirin. Dr. Shimada reported honorarium from MSD, Shionogi, Takeda, Daiichi-Sankyo, and Dainihon-Sumitomo, and serving as a consultant/advisory board member for Omron. Dr. Prabhakaran reported no relevant financial disclosures. Dr. Gaziano reported serving on the executive committee of the ARRIVE trial and as a consultant for and receiving speaking honoraria from Bayer.

[email protected]

AUSTIN, TEX. – Extracorporeal membrane oxygenation delivered during cardiopulmonary resuscitation allowed nearly twice as many patients to survive after discharge when compared against typical CPR-only procedures in a small, retrospective study.

“It’s no secret that conventional CPR is not terrifically successful,” Graham Peigh, a second-year medical student at Jefferson Medical College in Philadelphia, said during the Hot Topics in Pulmonary and Critical Care session at the annual meeting of the American College of Chest Physicians. “Extracorporeal membrane oxygenation [ECMO] gives patients a second chance at life.”

Mr. Peigh and his colleagues retrospectively analyzed 100 ECMO procedures performed on adults at a single teaching hospital during 2010-2013 and found that when ECMO was added to CPR, the survival rate to discharge went from 15% as calculated in a previously reported meta-analysis (J. Gen. Intern. Med. 1998;13:805-16) to 29% (P = .04).

When an arrested patient does not respond to CPR, cannulation through the femoral artery and vein can be combined with compressions to improve chances of survival.

In their analysis of ECMO delivered in an academic hospital setting, Mr. Peigh and his colleagues found that in the 24 cases in which ECMO was added to conventional CPR after the patients failed to respond to CPR alone, the survival rate with full neurologic recovery was 29%.

ECMO support was delivered in a number of scenarios, ranging from acute myocardial infarction to malignant arrhythmia to at least one case each of drug overdose induced cardiac arrest, septic shock, postcardiotomy failure, and acute rejection.

The ECMO support was provided for a mean of 5 days. The mean age for all patients studied was 47 years, and 15 were male. All cases followed a 24-hour hypothermia protocol.

Six of the ECMO-CPR patients died post ECMO of anoxic brain injury, stroke, or sepsis while still in the hospital, but the remaining seven patients (54%) survived after discharge and made full neurologic recoveries. The other 11 died during ECMO-CPR. During ECMO-CPR, 11 patients died of anoxic brain injury, stroke, metabolic acidosis, bowel necrosis, and family withdrawal of life support. Predictors of ECMO death were a pre-ECMO creatinine level of 1.7 mg/dL (P = .02) and the presence of acidosis (P = .04).

The ECMO survivor cohort also had what Mr. Peigh said were “encouraging” organ function results, with kidney and liver function remaining essentially unchanged after discharge.“Two of the patients who died of anoxic brain injuries were able to donate multiple organs for transplant,” Mr. Peigh said.

Previously reported ECMO data have shown there is at least a 20% increase in survival without notable neurologic effect, compared with conventional CPR (Lancet 2008;372:554-61; Crit. Care Med. 2011;39:1-7).

However, since these data were derived from centers where code teams were available at all times to treat a high volume of cardiac arrest patients, Mr. Peigh said the results – although indicative of the procedure’s value – “were not generalizable” to all institutions. But he noted that his and his colleagues’ study showed that even in institutions without a dedicated ECMO-CPR code team, ECMO-CPR resulted in demonstrably better outcomes for patients unresponsive to conventional CPR.

[email protected]

On Twitter @whitneymcknight

AUSTIN, TEX. – Extracorporeal membrane oxygenation delivered during cardiopulmonary resuscitation allowed nearly twice as many patients to survive after discharge when compared against typical CPR-only procedures in a small, retrospective study.

“It’s no secret that conventional CPR is not terrifically successful,” Graham Peigh, a second-year medical student at Jefferson Medical College in Philadelphia, said during the Hot Topics in Pulmonary and Critical Care session at the annual meeting of the American College of Chest Physicians. “Extracorporeal membrane oxygenation [ECMO] gives patients a second chance at life.”

Mr. Peigh and his colleagues retrospectively analyzed 100 ECMO procedures performed on adults at a single teaching hospital during 2010-2013 and found that when ECMO was added to CPR, the survival rate to discharge went from 15% as calculated in a previously reported meta-analysis (J. Gen. Intern. Med. 1998;13:805-16) to 29% (P = .04).

When an arrested patient does not respond to CPR, cannulation through the femoral artery and vein can be combined with compressions to improve chances of survival.

In their analysis of ECMO delivered in an academic hospital setting, Mr. Peigh and his colleagues found that in the 24 cases in which ECMO was added to conventional CPR after the patients failed to respond to CPR alone, the survival rate with full neurologic recovery was 29%.

ECMO support was delivered in a number of scenarios, ranging from acute myocardial infarction to malignant arrhythmia to at least one case each of drug overdose induced cardiac arrest, septic shock, postcardiotomy failure, and acute rejection.

The ECMO support was provided for a mean of 5 days. The mean age for all patients studied was 47 years, and 15 were male. All cases followed a 24-hour hypothermia protocol.

Six of the ECMO-CPR patients died post ECMO of anoxic brain injury, stroke, or sepsis while still in the hospital, but the remaining seven patients (54%) survived after discharge and made full neurologic recoveries. The other 11 died during ECMO-CPR. During ECMO-CPR, 11 patients died of anoxic brain injury, stroke, metabolic acidosis, bowel necrosis, and family withdrawal of life support. Predictors of ECMO death were a pre-ECMO creatinine level of 1.7 mg/dL (P = .02) and the presence of acidosis (P = .04).

The ECMO survivor cohort also had what Mr. Peigh said were “encouraging” organ function results, with kidney and liver function remaining essentially unchanged after discharge.“Two of the patients who died of anoxic brain injuries were able to donate multiple organs for transplant,” Mr. Peigh said.

Previously reported ECMO data have shown there is at least a 20% increase in survival without notable neurologic effect, compared with conventional CPR (Lancet 2008;372:554-61; Crit. Care Med. 2011;39:1-7).

However, since these data were derived from centers where code teams were available at all times to treat a high volume of cardiac arrest patients, Mr. Peigh said the results – although indicative of the procedure’s value – “were not generalizable” to all institutions. But he noted that his and his colleagues’ study showed that even in institutions without a dedicated ECMO-CPR code team, ECMO-CPR resulted in demonstrably better outcomes for patients unresponsive to conventional CPR.

[email protected]

On Twitter @whitneymcknight

AUSTIN, TEX. – Extracorporeal membrane oxygenation delivered during cardiopulmonary resuscitation allowed nearly twice as many patients to survive after discharge when compared against typical CPR-only procedures in a small, retrospective study.

“It’s no secret that conventional CPR is not terrifically successful,” Graham Peigh, a second-year medical student at Jefferson Medical College in Philadelphia, said during the Hot Topics in Pulmonary and Critical Care session at the annual meeting of the American College of Chest Physicians. “Extracorporeal membrane oxygenation [ECMO] gives patients a second chance at life.”

Mr. Peigh and his colleagues retrospectively analyzed 100 ECMO procedures performed on adults at a single teaching hospital during 2010-2013 and found that when ECMO was added to CPR, the survival rate to discharge went from 15% as calculated in a previously reported meta-analysis (J. Gen. Intern. Med. 1998;13:805-16) to 29% (P = .04).

When an arrested patient does not respond to CPR, cannulation through the femoral artery and vein can be combined with compressions to improve chances of survival.

In their analysis of ECMO delivered in an academic hospital setting, Mr. Peigh and his colleagues found that in the 24 cases in which ECMO was added to conventional CPR after the patients failed to respond to CPR alone, the survival rate with full neurologic recovery was 29%.

ECMO support was delivered in a number of scenarios, ranging from acute myocardial infarction to malignant arrhythmia to at least one case each of drug overdose induced cardiac arrest, septic shock, postcardiotomy failure, and acute rejection.

The ECMO support was provided for a mean of 5 days. The mean age for all patients studied was 47 years, and 15 were male. All cases followed a 24-hour hypothermia protocol.

Six of the ECMO-CPR patients died post ECMO of anoxic brain injury, stroke, or sepsis while still in the hospital, but the remaining seven patients (54%) survived after discharge and made full neurologic recoveries. The other 11 died during ECMO-CPR. During ECMO-CPR, 11 patients died of anoxic brain injury, stroke, metabolic acidosis, bowel necrosis, and family withdrawal of life support. Predictors of ECMO death were a pre-ECMO creatinine level of 1.7 mg/dL (P = .02) and the presence of acidosis (P = .04).

The ECMO survivor cohort also had what Mr. Peigh said were “encouraging” organ function results, with kidney and liver function remaining essentially unchanged after discharge.“Two of the patients who died of anoxic brain injuries were able to donate multiple organs for transplant,” Mr. Peigh said.

Previously reported ECMO data have shown there is at least a 20% increase in survival without notable neurologic effect, compared with conventional CPR (Lancet 2008;372:554-61; Crit. Care Med. 2011;39:1-7).

However, since these data were derived from centers where code teams were available at all times to treat a high volume of cardiac arrest patients, Mr. Peigh said the results – although indicative of the procedure’s value – “were not generalizable” to all institutions. But he noted that his and his colleagues’ study showed that even in institutions without a dedicated ECMO-CPR code team, ECMO-CPR resulted in demonstrably better outcomes for patients unresponsive to conventional CPR.

[email protected]

On Twitter @whitneymcknight