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New twists in medical management of PAD
SNOWMASS, COLO. – Be leery of lowering high blood pressure too much in patients with lower extremity peripheral artery disease, Robert A. Vogel, MD, cautioned the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology
“We used to worry about lowering blood pressure too much in [coronary artery disease]. I need to rekindle that thought, because you want to be very careful about lowering blood pressure too much in PAD,” said Dr. Vogel, a preventive cardiology specialist at the University of Colorado, Denver.
He cited a recent reanalysis of data from the landmark ALLHAT (Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial) conducted by investigators at Stanford (Calif.) University. During a median 4.3 years of prospective follow-up of 33,357 participants with a median baseline blood pressure of 146/84 mm Hg, the risk of the composite endpoint of lower extremity PAD events – defined as PAD-related hospitalization, revascularization procedures, medical treatment, or PAD-related death – was increased by 26% in patients with a systolic blood pressure below 120 mm Hg, compared with an SBP of 120-129 mm Hg.
In a similar Cox regression analysis, the risk of PAD events was increased by 72% in patients with a diastolic blood pressure below 60 mm Hg, compared with that of patients with a DBP of 70-79 mm Hg, and to a lesser, albeit still statistically significant and clinically meaningful, extent in those with a DBP of 60-69 mm Hg (Circulation. 2018;138:1805-14).
Dr. Vogel’s cautionary note about overzealous blood pressure–lowering was one of several developments he highlighted since publication of the 2016 American Heart Association/American College of Cardiology guidelines on the medical management of lower extremity PAD (J Am Coll Cardiol. 2017;69:1465-508). Others include new data demonstrating that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy shows particularly strong benefit in the patient subgroup with PAD, as did rivaroxaban (Xarelto) at 2.5 mg b.i.d. plus aspirin 100 mg/day in the COMPASS trial.
Also, the final week of 2018 saw publication of the ACC Expert Consensus Decision Pathway on Tobacco Cessation (J Am Coll Cardiol. 2018 Dec 25;72[25]:3332-65), which Dr. Vogel considers an exemplary document every physician who cares for patients with PAD ought to read.
The Class I recommendations in the ACC/AHA guidelines for medical management of PAD include introducing a supervised exercise program before resorting to a revascularization procedure, providing advice on smoking cessation at every visit, antiplatelet therapy, a high-intensity statin, cilostazol for claudication, and coordination of the patient’s diabetes care with an endocrinologist or primary care physician.
Numerous studies have documented that physicians by and large aren’t doing so well in bringing these evidence-based therapies to bear. For example, a recent study of 155,647 Veterans Affairs patients with new-onset PAD found that 28% weren’t on a statin. Only 18.4% with PAD and comorbid coronary or carotid disease were on a high-intensity statin, as were just 6.4% with PAD only. In a multivariate adjusted analysis, high-intensity statin users had a 33% lower risk of amputation and a 26% lower risk of mortality, compared with statin nonusers (Circulation. 2018;137:1435-46).
It’s as if there’s a widespread failure to appreciate the substantial morbidity and mortality conferred by PAD, so Dr. Vogel put it into perspective: “In broad strokes, atherosclerosis starts in the aorta, moves to the coronaries, goes to the carotids, and ends up in the legs. By the time you have lower-extremity atherosclerosis, you are a vasculopath,” he explained.
Smoking cessation
“Lower-extremity PAD is a disease of smoking. Cholesterol goes to the heart, blood pressure goes to the head, and smoking goes to the legs, in broad strokes. Current smokers are 12 times more likely to have PAD than never smokers. And if you stop smoking, you reduce death by more than 50%,” the cardiologist said.
“You’ve got to get these folks to stop smoking, a difficult task. I do my clinical work at a VA hospital, and I can tell you this is a challenge,” he continued.
The new ACC Expert Consensus report is a boon in this regard.
“It’s not that long, and it’s very, very good. Very helpful. It’s not theoretical, it’s very practical,” according to Dr. Vogel. But he didn’t sugar coat what’s involved in getting PAD patients to quit smoking.
“At best, per round of smoking cessation, with pharmacology as well as multiple-session counseling, you can get 15%-20% abstinence per cycle. And it often takes many cycles of counseling to get people to stop smoking,” he added.
Low-dose rivaroxaban plus aspirin
Dr. Vogel believes the combination of low-dose rivaroxaban plus aspirin is worthy of serious consideration in patients with PAD on the strength of the COMPASS trial, a randomized, double-blind study of more than 27,000 patients with stable CAD, 27% of whom also had PAD. The PAD group on rivaroxaban 2.5 mg b.i.d. plus aspirin had a 28% relative risk reduction in the composite endpoint of cardiovascular death, stroke, or MI, compared with those on aspirin plus placebo. This benefit came at a cost of a 51% increase in the risk of major bleeding, but not fatal bleeding or bleeding causing critical damage to the brain or other organs.
Taking into account both the primary efficacy and severe bleeding rates, the net clinical benefit of low-dose rivaroxaban was 20%. The absolute risk reduction was larger in the PAD subgroup than in those with CAD-only because of their greater baseline risk (N Engl J Med. 2017;377:1319-30).
At present a 2.5-mg dose of rivaroxaban isn’t commercially available, so patients have to cut higher-dose tablets, but on the strength of the COMPASS results, a 2.5-mg tablet is in the works, Dr. Vogel said.
PCSK9 inhibitors
In the FOURIER trial of evolocumab (Praluent) versus placebo on top of maximally tolerated statin therapy in more than 27,000 patients with atherosclerotic disease, including 3,642 with PAD, the rate of MALE (major adverse limb events) was reduced by 42% in the evolocumab group, with a number-needed-to-treat in order to prevent one additional MALE event of only 16 (Circulation. 2018;137:338-50).
“This is a subgroup that really benefits from PCSK9 inhibition. It’s something to think about,” Dr. Vogel said.
Dr. Vogel reported serving as a paid consultant to the National Football League and the Pritikin Longevity Center, receiving research grants from Sanofi, and serving on speakers bureaus for Regeneron and Sanofi.
SNOWMASS, COLO. – Be leery of lowering high blood pressure too much in patients with lower extremity peripheral artery disease, Robert A. Vogel, MD, cautioned the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology
“We used to worry about lowering blood pressure too much in [coronary artery disease]. I need to rekindle that thought, because you want to be very careful about lowering blood pressure too much in PAD,” said Dr. Vogel, a preventive cardiology specialist at the University of Colorado, Denver.
He cited a recent reanalysis of data from the landmark ALLHAT (Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial) conducted by investigators at Stanford (Calif.) University. During a median 4.3 years of prospective follow-up of 33,357 participants with a median baseline blood pressure of 146/84 mm Hg, the risk of the composite endpoint of lower extremity PAD events – defined as PAD-related hospitalization, revascularization procedures, medical treatment, or PAD-related death – was increased by 26% in patients with a systolic blood pressure below 120 mm Hg, compared with an SBP of 120-129 mm Hg.
In a similar Cox regression analysis, the risk of PAD events was increased by 72% in patients with a diastolic blood pressure below 60 mm Hg, compared with that of patients with a DBP of 70-79 mm Hg, and to a lesser, albeit still statistically significant and clinically meaningful, extent in those with a DBP of 60-69 mm Hg (Circulation. 2018;138:1805-14).
Dr. Vogel’s cautionary note about overzealous blood pressure–lowering was one of several developments he highlighted since publication of the 2016 American Heart Association/American College of Cardiology guidelines on the medical management of lower extremity PAD (J Am Coll Cardiol. 2017;69:1465-508). Others include new data demonstrating that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy shows particularly strong benefit in the patient subgroup with PAD, as did rivaroxaban (Xarelto) at 2.5 mg b.i.d. plus aspirin 100 mg/day in the COMPASS trial.
Also, the final week of 2018 saw publication of the ACC Expert Consensus Decision Pathway on Tobacco Cessation (J Am Coll Cardiol. 2018 Dec 25;72[25]:3332-65), which Dr. Vogel considers an exemplary document every physician who cares for patients with PAD ought to read.
The Class I recommendations in the ACC/AHA guidelines for medical management of PAD include introducing a supervised exercise program before resorting to a revascularization procedure, providing advice on smoking cessation at every visit, antiplatelet therapy, a high-intensity statin, cilostazol for claudication, and coordination of the patient’s diabetes care with an endocrinologist or primary care physician.
Numerous studies have documented that physicians by and large aren’t doing so well in bringing these evidence-based therapies to bear. For example, a recent study of 155,647 Veterans Affairs patients with new-onset PAD found that 28% weren’t on a statin. Only 18.4% with PAD and comorbid coronary or carotid disease were on a high-intensity statin, as were just 6.4% with PAD only. In a multivariate adjusted analysis, high-intensity statin users had a 33% lower risk of amputation and a 26% lower risk of mortality, compared with statin nonusers (Circulation. 2018;137:1435-46).
It’s as if there’s a widespread failure to appreciate the substantial morbidity and mortality conferred by PAD, so Dr. Vogel put it into perspective: “In broad strokes, atherosclerosis starts in the aorta, moves to the coronaries, goes to the carotids, and ends up in the legs. By the time you have lower-extremity atherosclerosis, you are a vasculopath,” he explained.
Smoking cessation
“Lower-extremity PAD is a disease of smoking. Cholesterol goes to the heart, blood pressure goes to the head, and smoking goes to the legs, in broad strokes. Current smokers are 12 times more likely to have PAD than never smokers. And if you stop smoking, you reduce death by more than 50%,” the cardiologist said.
“You’ve got to get these folks to stop smoking, a difficult task. I do my clinical work at a VA hospital, and I can tell you this is a challenge,” he continued.
The new ACC Expert Consensus report is a boon in this regard.
“It’s not that long, and it’s very, very good. Very helpful. It’s not theoretical, it’s very practical,” according to Dr. Vogel. But he didn’t sugar coat what’s involved in getting PAD patients to quit smoking.
“At best, per round of smoking cessation, with pharmacology as well as multiple-session counseling, you can get 15%-20% abstinence per cycle. And it often takes many cycles of counseling to get people to stop smoking,” he added.
Low-dose rivaroxaban plus aspirin
Dr. Vogel believes the combination of low-dose rivaroxaban plus aspirin is worthy of serious consideration in patients with PAD on the strength of the COMPASS trial, a randomized, double-blind study of more than 27,000 patients with stable CAD, 27% of whom also had PAD. The PAD group on rivaroxaban 2.5 mg b.i.d. plus aspirin had a 28% relative risk reduction in the composite endpoint of cardiovascular death, stroke, or MI, compared with those on aspirin plus placebo. This benefit came at a cost of a 51% increase in the risk of major bleeding, but not fatal bleeding or bleeding causing critical damage to the brain or other organs.
Taking into account both the primary efficacy and severe bleeding rates, the net clinical benefit of low-dose rivaroxaban was 20%. The absolute risk reduction was larger in the PAD subgroup than in those with CAD-only because of their greater baseline risk (N Engl J Med. 2017;377:1319-30).
At present a 2.5-mg dose of rivaroxaban isn’t commercially available, so patients have to cut higher-dose tablets, but on the strength of the COMPASS results, a 2.5-mg tablet is in the works, Dr. Vogel said.
PCSK9 inhibitors
In the FOURIER trial of evolocumab (Praluent) versus placebo on top of maximally tolerated statin therapy in more than 27,000 patients with atherosclerotic disease, including 3,642 with PAD, the rate of MALE (major adverse limb events) was reduced by 42% in the evolocumab group, with a number-needed-to-treat in order to prevent one additional MALE event of only 16 (Circulation. 2018;137:338-50).
“This is a subgroup that really benefits from PCSK9 inhibition. It’s something to think about,” Dr. Vogel said.
Dr. Vogel reported serving as a paid consultant to the National Football League and the Pritikin Longevity Center, receiving research grants from Sanofi, and serving on speakers bureaus for Regeneron and Sanofi.
SNOWMASS, COLO. – Be leery of lowering high blood pressure too much in patients with lower extremity peripheral artery disease, Robert A. Vogel, MD, cautioned the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology
“We used to worry about lowering blood pressure too much in [coronary artery disease]. I need to rekindle that thought, because you want to be very careful about lowering blood pressure too much in PAD,” said Dr. Vogel, a preventive cardiology specialist at the University of Colorado, Denver.
He cited a recent reanalysis of data from the landmark ALLHAT (Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial) conducted by investigators at Stanford (Calif.) University. During a median 4.3 years of prospective follow-up of 33,357 participants with a median baseline blood pressure of 146/84 mm Hg, the risk of the composite endpoint of lower extremity PAD events – defined as PAD-related hospitalization, revascularization procedures, medical treatment, or PAD-related death – was increased by 26% in patients with a systolic blood pressure below 120 mm Hg, compared with an SBP of 120-129 mm Hg.
In a similar Cox regression analysis, the risk of PAD events was increased by 72% in patients with a diastolic blood pressure below 60 mm Hg, compared with that of patients with a DBP of 70-79 mm Hg, and to a lesser, albeit still statistically significant and clinically meaningful, extent in those with a DBP of 60-69 mm Hg (Circulation. 2018;138:1805-14).
Dr. Vogel’s cautionary note about overzealous blood pressure–lowering was one of several developments he highlighted since publication of the 2016 American Heart Association/American College of Cardiology guidelines on the medical management of lower extremity PAD (J Am Coll Cardiol. 2017;69:1465-508). Others include new data demonstrating that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy shows particularly strong benefit in the patient subgroup with PAD, as did rivaroxaban (Xarelto) at 2.5 mg b.i.d. plus aspirin 100 mg/day in the COMPASS trial.
Also, the final week of 2018 saw publication of the ACC Expert Consensus Decision Pathway on Tobacco Cessation (J Am Coll Cardiol. 2018 Dec 25;72[25]:3332-65), which Dr. Vogel considers an exemplary document every physician who cares for patients with PAD ought to read.
The Class I recommendations in the ACC/AHA guidelines for medical management of PAD include introducing a supervised exercise program before resorting to a revascularization procedure, providing advice on smoking cessation at every visit, antiplatelet therapy, a high-intensity statin, cilostazol for claudication, and coordination of the patient’s diabetes care with an endocrinologist or primary care physician.
Numerous studies have documented that physicians by and large aren’t doing so well in bringing these evidence-based therapies to bear. For example, a recent study of 155,647 Veterans Affairs patients with new-onset PAD found that 28% weren’t on a statin. Only 18.4% with PAD and comorbid coronary or carotid disease were on a high-intensity statin, as were just 6.4% with PAD only. In a multivariate adjusted analysis, high-intensity statin users had a 33% lower risk of amputation and a 26% lower risk of mortality, compared with statin nonusers (Circulation. 2018;137:1435-46).
It’s as if there’s a widespread failure to appreciate the substantial morbidity and mortality conferred by PAD, so Dr. Vogel put it into perspective: “In broad strokes, atherosclerosis starts in the aorta, moves to the coronaries, goes to the carotids, and ends up in the legs. By the time you have lower-extremity atherosclerosis, you are a vasculopath,” he explained.
Smoking cessation
“Lower-extremity PAD is a disease of smoking. Cholesterol goes to the heart, blood pressure goes to the head, and smoking goes to the legs, in broad strokes. Current smokers are 12 times more likely to have PAD than never smokers. And if you stop smoking, you reduce death by more than 50%,” the cardiologist said.
“You’ve got to get these folks to stop smoking, a difficult task. I do my clinical work at a VA hospital, and I can tell you this is a challenge,” he continued.
The new ACC Expert Consensus report is a boon in this regard.
“It’s not that long, and it’s very, very good. Very helpful. It’s not theoretical, it’s very practical,” according to Dr. Vogel. But he didn’t sugar coat what’s involved in getting PAD patients to quit smoking.
“At best, per round of smoking cessation, with pharmacology as well as multiple-session counseling, you can get 15%-20% abstinence per cycle. And it often takes many cycles of counseling to get people to stop smoking,” he added.
Low-dose rivaroxaban plus aspirin
Dr. Vogel believes the combination of low-dose rivaroxaban plus aspirin is worthy of serious consideration in patients with PAD on the strength of the COMPASS trial, a randomized, double-blind study of more than 27,000 patients with stable CAD, 27% of whom also had PAD. The PAD group on rivaroxaban 2.5 mg b.i.d. plus aspirin had a 28% relative risk reduction in the composite endpoint of cardiovascular death, stroke, or MI, compared with those on aspirin plus placebo. This benefit came at a cost of a 51% increase in the risk of major bleeding, but not fatal bleeding or bleeding causing critical damage to the brain or other organs.
Taking into account both the primary efficacy and severe bleeding rates, the net clinical benefit of low-dose rivaroxaban was 20%. The absolute risk reduction was larger in the PAD subgroup than in those with CAD-only because of their greater baseline risk (N Engl J Med. 2017;377:1319-30).
At present a 2.5-mg dose of rivaroxaban isn’t commercially available, so patients have to cut higher-dose tablets, but on the strength of the COMPASS results, a 2.5-mg tablet is in the works, Dr. Vogel said.
PCSK9 inhibitors
In the FOURIER trial of evolocumab (Praluent) versus placebo on top of maximally tolerated statin therapy in more than 27,000 patients with atherosclerotic disease, including 3,642 with PAD, the rate of MALE (major adverse limb events) was reduced by 42% in the evolocumab group, with a number-needed-to-treat in order to prevent one additional MALE event of only 16 (Circulation. 2018;137:338-50).
“This is a subgroup that really benefits from PCSK9 inhibition. It’s something to think about,” Dr. Vogel said.
Dr. Vogel reported serving as a paid consultant to the National Football League and the Pritikin Longevity Center, receiving research grants from Sanofi, and serving on speakers bureaus for Regeneron and Sanofi.
EXPERT ANALYSIS FROM ACC SNOWMASS 2019
Major message: Most heart failure is preventable
SNOWMASS, COLO. – More than 960,000 new cases of heart failure will occur in the United States this year – and most of them could have been prevented, Gregg C. Fonarow, MD, asserted at the Annual Cardiovascular Conference at Snowmass.
Preventing heart failure doesn’t require heroic measures. It entails identifying high-risk individuals while they are still asymptomatic and free of structural heart disease – that is, patients who are stage A, pre–heart failure, in the American College of Cardiology/American Heart Association classification system for heart failure – and then addressing their modifiable risk factors via evidence-based, guideline-directed medical therapy, said Dr. Fonarow, professor of cardiovascular medicine and cochief of cardiology at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.
A special word about obesity: A Framingham Heart Study analysis concluded that, after controlling for other cardiovascular risk factors, obese individuals had double the risk of new-onset heart failure, compared with normal weight subjects, during a mean follow-up of 14 years. For each one-unit increase in body mass index, the adjusted risk of heart failure climbed by 5% in men and 7% in women (N Engl J Med. 2002 Aug 1;347[5]:305-13). And that spells trouble down the line.
“You can imagine, with the marked increase in overweight and obesity status now affecting over half of U.S. adults, what this will mean for a potential rise in heart failure prevalence and incidence unless we do something further to modify this,” the cardiologist observed.
Dr. Fonarow is a member of the writing group for the ACC/AHA guidelines on management of heart failure. They recommend as a risk reduction strategy identification of patients with stage A pre–heart failure and addressing their risk factors: treating their hypertension and lipid disorders, gaining control over metabolic syndrome, discouraging heavy alcohol intake, and encouraging smoking cessation and regular exercise (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-239).
What kind of reduction in heart failure risk can be expected via these measures?
Antihypertensive therapy
More than a quarter century ago, the landmark SHEP trial (Systolic Hypertension in the Elderly Program) in more than 4,700 hypertensive seniors showed that treatment with diuretics and beta-blockers resulted in a 49% reduction in heart failure events, compared with placebo. And this has been a consistent finding in other studies: A meta-analysis of all 12 major randomized trials of antihypertensive therapy conducted over a 20-year period showed that treatment resulted in a whopping 52% reduction in the risk of heart failure (J Am Coll Cardiol. 1995 Apr; 27[5]:1214-8).
“If you ask most people why they’re on antihypertensive medication, they say, ‘Oh, to prevent heart attacks and stroke.’ But in fact the greatest relative risk reduction that we see is this remarkable reduction in the risk of developing heart failure with blood pressure treatment,” Dr. Fonarow said.
There has been some argument within medicine as to whether aggressive blood pressure lowering is appropriate in individuals over age 80. But in the HYVET trial (Hypertension in the Very Elderly Trial) conducted in that age group, the use of diuretics and/or ACE inhibitors to lower systolic blood pressure from roughly 155 mm Hg to 145 mm Hg resulted in a dramatic 64% reduction in the rate of new-onset heart failure (N Engl J Med. 2008 May 1;358[18]:1887-98).
How low to go with blood pressure reduction in order to maximize the heart failure risk reduction benefit? In the SPRINT trial (Systolic Blood Pressure Intervention Trial) of 9,361 hypertensive patients with a history of cardiovascular disease or multiple risk factors, participants randomized to a goal of less than 120 mm Hg enjoyed a 38% lower risk of heart failure events, compared with those whose target was less than 140 mm Hg (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
A secondary analysis from SPRINT showed that the risk of acute decompensated heart failure was 37% lower in patients treated to the target of less than 120 mm Hg. That finding takes on particular importance because SPRINT participants who developed acute decompensated heart failure had a 27-fold increase in cardiovascular death (Circ Heart Fail. 2017 Apr; doi: 10.1161/CIRCHEARTFAILURE.116.003613).
Lipid lowering
A meta-analysis of four major, randomized clinical trials of intensive versus moderate statin therapy in 27,546 patients with stable coronary artery disease or acute coronary syndrome concluded that intensive therapy resulted in a 27% reduction in the risk of hospitalization for heart failure (J Am Coll Cardiol. 2006 Jun 6;47[11]:2326-31).
SGLT-2 inhibition
Until the randomized EMPA-REG OUTCOME trial of the sodium-glucose transporter 2 (SGLT-2) inhibitor empagliflozin(Jardiance), no glucose-lowering drug available for treatment of type 2 diabetes had shown any benefit in terms of reducing diabetic patients’ elevated risk of heart failure. Neither had weight loss. Abundant evidence showed that glycemic control had no impact on the risk of heart failure events. So EMPA-REG OUTCOME was cause for celebration among heart failure specialists, with its demonstration of a 35% reduction in the risk of hospitalization for heart failure, compared with placebo in more than 7,000 randomized patients. The risk of death because of heart failure was chopped by 68%. Sharp reductions in other cardiovascular events were also seen with empagliflozin (N Engl J Med. 2015 Nov 26;373[22]:2117-28).
Similar benefits were subsequently documented with another SGLT-2 inhibitor, canagliflozin(Invokana), in the CANVAS study program (N Engl J Med. 2017 Aug 17;377:644-57).
The reduction in cardiovascular mortality achieved with empagliflozin in EMPA-REG OUTCOME was actually bigger than seen with ACE inhibitors and angiotensin-receptor blockers (ARBs) in earlier landmark heart failure trials (Eur J Heart Fail. 2017 Jan;19[1]:43-53).
Dr. Fonarow views these data as “compelling.” These trials mark a huge step forward in the prevention of heart failure.
“We now for the first time in patients with diabetes have the ability to markedly prevent heart failure as well as cardiovascular death,” the cardiologist commented. “It is critical for cardiologists and heart failure specialists to play an active role in this [pharmacologic diabetes] management, as choice of therapy is a key determinant of outcomes, including survival.”
ACE inhibitors and ARBs
The ACC/AHA heart failure guidelines give a Class I recommendation to the routine use of ACE inhibitors or ARBs in patients at high risk for developing heart failure because of a history of diabetes, hypertension with associated cardiovascular risk factors, or any form of atherosclerotic vascular disease.
Lifestyle modification
Heavy drinking is known to raise the risk of heart failure. However, moderate alcohol consumption may be protective. In a classic prospective cohort study, individuals who reported consuming 1.5-4 drinks per day in the previous month had a 47% reduction in subsequent new-onset heart failure, compared with teetotalers in a multivariate analysis adjusted for conventional cardiovascular risk factors. Those who drank less than 1.5 drinks per day had a 21% reduction in heart failure risk, compared with the nondrinkers (JAMA. 2001 Apr 18;285[15]:1971-7).
In the prospective observational Physicians’ Health Study of nearly 21,000 men, adherence to six modifiable healthy lifestyle factors was associated with an incremental stepwise reduction in lifetime risk of developing heart failure. The six lifestyle factors – a forerunner of the AHA’s Life’s Simple 7 – were maintaining a normal body weight, stopping smoking, getting exercise, drinking alcohol in moderation, consuming breakfast cereals, and eating fruits and vegetables. Male physicians who shunned all six had a 21.2% lifetime risk of heart failure; those who followed at least four of the healthy lifestyle factors had a 10.1% risk (JAMA 2009 Jul 22;302[4]:394-400).
In a separate analysis from the Physicians’ Health Study, men who engaged in vigorous exercise to the point of breaking a sweat as little as one to three times per month had an 18% lower risk of developing heart failure during follow-up, compared with inactive men (Circulation 2009 Jan 6;119[1]:44-52).
What’s next in prevention of heart failure
Heart failure is one of the most expensive health care problems in the United States, and one of the deadliest. Today an estimated 6.5 million Americans have symptomatic heart failure. But that’s just the tip of the iceberg.
“Countless millions more are likely to manifest heart failure in the future,” Dr. Fonarow warned, noting the vast prevalence of identifiable risk factors.
It’s time for a high-visibility public health campaign designed to foster community education and engagement regarding heart failure prevention, he added.
“We have a lot of action and events around preventing atherosclerotic cardiovascular disease. But can you think of any campaign you’ve seen focusing specifically on heart failure? Heart failure isn’t one of the endpoints in the ACC/AHA Atherosclerotic Cardiovascular Disease Risk Calculator or even the new hypertension risk calculator, so we need to take this a whole lot more seriously,” the cardiologist said.
The 2017 focused update of the ACC/AHA heart failure guidelines endorsed a novel strategy of primary care–centered, biomarker-based screening of patients with cardiovascular risk factors as a means of triggering early intervention to prevent heart failure (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803). This strategy, which received a Class IIa recommendation, involves screening measurement of a natriuretic peptide biomarker.
The recommendation was based on evidence including the STOP-HF randomized trial (St. Vincent’s Screening to Prevent Heart Failure Study), in which 1,374 asymptomatic Irish patients with cardiovascular risk factors were randomized to routine primary care or primary care plus screening with brain-type natriuretic peptide testing. Patients with a brain-type natriuretic peptide level of 50 pg/mL or more were directed to team-based care involving a collaboration between their primary care physician and a specialist cardiovascular service focused on optimizing guideline-directed medical therapy. During a mean follow-up of 4.2 years, the primary endpoint of new-onset left ventricular dysfunction occurred in 5.3% of the intervention group and 8.7% of controls, for a 45% relative risk reduction (JAMA 2013 Jul 3;310[1]:66-74).
Dr. Fonarow reported receiving research grants from and serving as a consultant to the National Heart, Lung, and Blood Institute and a handful of medical companies.
SNOWMASS, COLO. – More than 960,000 new cases of heart failure will occur in the United States this year – and most of them could have been prevented, Gregg C. Fonarow, MD, asserted at the Annual Cardiovascular Conference at Snowmass.
Preventing heart failure doesn’t require heroic measures. It entails identifying high-risk individuals while they are still asymptomatic and free of structural heart disease – that is, patients who are stage A, pre–heart failure, in the American College of Cardiology/American Heart Association classification system for heart failure – and then addressing their modifiable risk factors via evidence-based, guideline-directed medical therapy, said Dr. Fonarow, professor of cardiovascular medicine and cochief of cardiology at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.
A special word about obesity: A Framingham Heart Study analysis concluded that, after controlling for other cardiovascular risk factors, obese individuals had double the risk of new-onset heart failure, compared with normal weight subjects, during a mean follow-up of 14 years. For each one-unit increase in body mass index, the adjusted risk of heart failure climbed by 5% in men and 7% in women (N Engl J Med. 2002 Aug 1;347[5]:305-13). And that spells trouble down the line.
“You can imagine, with the marked increase in overweight and obesity status now affecting over half of U.S. adults, what this will mean for a potential rise in heart failure prevalence and incidence unless we do something further to modify this,” the cardiologist observed.
Dr. Fonarow is a member of the writing group for the ACC/AHA guidelines on management of heart failure. They recommend as a risk reduction strategy identification of patients with stage A pre–heart failure and addressing their risk factors: treating their hypertension and lipid disorders, gaining control over metabolic syndrome, discouraging heavy alcohol intake, and encouraging smoking cessation and regular exercise (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-239).
What kind of reduction in heart failure risk can be expected via these measures?
Antihypertensive therapy
More than a quarter century ago, the landmark SHEP trial (Systolic Hypertension in the Elderly Program) in more than 4,700 hypertensive seniors showed that treatment with diuretics and beta-blockers resulted in a 49% reduction in heart failure events, compared with placebo. And this has been a consistent finding in other studies: A meta-analysis of all 12 major randomized trials of antihypertensive therapy conducted over a 20-year period showed that treatment resulted in a whopping 52% reduction in the risk of heart failure (J Am Coll Cardiol. 1995 Apr; 27[5]:1214-8).
“If you ask most people why they’re on antihypertensive medication, they say, ‘Oh, to prevent heart attacks and stroke.’ But in fact the greatest relative risk reduction that we see is this remarkable reduction in the risk of developing heart failure with blood pressure treatment,” Dr. Fonarow said.
There has been some argument within medicine as to whether aggressive blood pressure lowering is appropriate in individuals over age 80. But in the HYVET trial (Hypertension in the Very Elderly Trial) conducted in that age group, the use of diuretics and/or ACE inhibitors to lower systolic blood pressure from roughly 155 mm Hg to 145 mm Hg resulted in a dramatic 64% reduction in the rate of new-onset heart failure (N Engl J Med. 2008 May 1;358[18]:1887-98).
How low to go with blood pressure reduction in order to maximize the heart failure risk reduction benefit? In the SPRINT trial (Systolic Blood Pressure Intervention Trial) of 9,361 hypertensive patients with a history of cardiovascular disease or multiple risk factors, participants randomized to a goal of less than 120 mm Hg enjoyed a 38% lower risk of heart failure events, compared with those whose target was less than 140 mm Hg (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
A secondary analysis from SPRINT showed that the risk of acute decompensated heart failure was 37% lower in patients treated to the target of less than 120 mm Hg. That finding takes on particular importance because SPRINT participants who developed acute decompensated heart failure had a 27-fold increase in cardiovascular death (Circ Heart Fail. 2017 Apr; doi: 10.1161/CIRCHEARTFAILURE.116.003613).
Lipid lowering
A meta-analysis of four major, randomized clinical trials of intensive versus moderate statin therapy in 27,546 patients with stable coronary artery disease or acute coronary syndrome concluded that intensive therapy resulted in a 27% reduction in the risk of hospitalization for heart failure (J Am Coll Cardiol. 2006 Jun 6;47[11]:2326-31).
SGLT-2 inhibition
Until the randomized EMPA-REG OUTCOME trial of the sodium-glucose transporter 2 (SGLT-2) inhibitor empagliflozin(Jardiance), no glucose-lowering drug available for treatment of type 2 diabetes had shown any benefit in terms of reducing diabetic patients’ elevated risk of heart failure. Neither had weight loss. Abundant evidence showed that glycemic control had no impact on the risk of heart failure events. So EMPA-REG OUTCOME was cause for celebration among heart failure specialists, with its demonstration of a 35% reduction in the risk of hospitalization for heart failure, compared with placebo in more than 7,000 randomized patients. The risk of death because of heart failure was chopped by 68%. Sharp reductions in other cardiovascular events were also seen with empagliflozin (N Engl J Med. 2015 Nov 26;373[22]:2117-28).
Similar benefits were subsequently documented with another SGLT-2 inhibitor, canagliflozin(Invokana), in the CANVAS study program (N Engl J Med. 2017 Aug 17;377:644-57).
The reduction in cardiovascular mortality achieved with empagliflozin in EMPA-REG OUTCOME was actually bigger than seen with ACE inhibitors and angiotensin-receptor blockers (ARBs) in earlier landmark heart failure trials (Eur J Heart Fail. 2017 Jan;19[1]:43-53).
Dr. Fonarow views these data as “compelling.” These trials mark a huge step forward in the prevention of heart failure.
“We now for the first time in patients with diabetes have the ability to markedly prevent heart failure as well as cardiovascular death,” the cardiologist commented. “It is critical for cardiologists and heart failure specialists to play an active role in this [pharmacologic diabetes] management, as choice of therapy is a key determinant of outcomes, including survival.”
ACE inhibitors and ARBs
The ACC/AHA heart failure guidelines give a Class I recommendation to the routine use of ACE inhibitors or ARBs in patients at high risk for developing heart failure because of a history of diabetes, hypertension with associated cardiovascular risk factors, or any form of atherosclerotic vascular disease.
Lifestyle modification
Heavy drinking is known to raise the risk of heart failure. However, moderate alcohol consumption may be protective. In a classic prospective cohort study, individuals who reported consuming 1.5-4 drinks per day in the previous month had a 47% reduction in subsequent new-onset heart failure, compared with teetotalers in a multivariate analysis adjusted for conventional cardiovascular risk factors. Those who drank less than 1.5 drinks per day had a 21% reduction in heart failure risk, compared with the nondrinkers (JAMA. 2001 Apr 18;285[15]:1971-7).
In the prospective observational Physicians’ Health Study of nearly 21,000 men, adherence to six modifiable healthy lifestyle factors was associated with an incremental stepwise reduction in lifetime risk of developing heart failure. The six lifestyle factors – a forerunner of the AHA’s Life’s Simple 7 – were maintaining a normal body weight, stopping smoking, getting exercise, drinking alcohol in moderation, consuming breakfast cereals, and eating fruits and vegetables. Male physicians who shunned all six had a 21.2% lifetime risk of heart failure; those who followed at least four of the healthy lifestyle factors had a 10.1% risk (JAMA 2009 Jul 22;302[4]:394-400).
In a separate analysis from the Physicians’ Health Study, men who engaged in vigorous exercise to the point of breaking a sweat as little as one to three times per month had an 18% lower risk of developing heart failure during follow-up, compared with inactive men (Circulation 2009 Jan 6;119[1]:44-52).
What’s next in prevention of heart failure
Heart failure is one of the most expensive health care problems in the United States, and one of the deadliest. Today an estimated 6.5 million Americans have symptomatic heart failure. But that’s just the tip of the iceberg.
“Countless millions more are likely to manifest heart failure in the future,” Dr. Fonarow warned, noting the vast prevalence of identifiable risk factors.
It’s time for a high-visibility public health campaign designed to foster community education and engagement regarding heart failure prevention, he added.
“We have a lot of action and events around preventing atherosclerotic cardiovascular disease. But can you think of any campaign you’ve seen focusing specifically on heart failure? Heart failure isn’t one of the endpoints in the ACC/AHA Atherosclerotic Cardiovascular Disease Risk Calculator or even the new hypertension risk calculator, so we need to take this a whole lot more seriously,” the cardiologist said.
The 2017 focused update of the ACC/AHA heart failure guidelines endorsed a novel strategy of primary care–centered, biomarker-based screening of patients with cardiovascular risk factors as a means of triggering early intervention to prevent heart failure (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803). This strategy, which received a Class IIa recommendation, involves screening measurement of a natriuretic peptide biomarker.
The recommendation was based on evidence including the STOP-HF randomized trial (St. Vincent’s Screening to Prevent Heart Failure Study), in which 1,374 asymptomatic Irish patients with cardiovascular risk factors were randomized to routine primary care or primary care plus screening with brain-type natriuretic peptide testing. Patients with a brain-type natriuretic peptide level of 50 pg/mL or more were directed to team-based care involving a collaboration between their primary care physician and a specialist cardiovascular service focused on optimizing guideline-directed medical therapy. During a mean follow-up of 4.2 years, the primary endpoint of new-onset left ventricular dysfunction occurred in 5.3% of the intervention group and 8.7% of controls, for a 45% relative risk reduction (JAMA 2013 Jul 3;310[1]:66-74).
Dr. Fonarow reported receiving research grants from and serving as a consultant to the National Heart, Lung, and Blood Institute and a handful of medical companies.
SNOWMASS, COLO. – More than 960,000 new cases of heart failure will occur in the United States this year – and most of them could have been prevented, Gregg C. Fonarow, MD, asserted at the Annual Cardiovascular Conference at Snowmass.
Preventing heart failure doesn’t require heroic measures. It entails identifying high-risk individuals while they are still asymptomatic and free of structural heart disease – that is, patients who are stage A, pre–heart failure, in the American College of Cardiology/American Heart Association classification system for heart failure – and then addressing their modifiable risk factors via evidence-based, guideline-directed medical therapy, said Dr. Fonarow, professor of cardiovascular medicine and cochief of cardiology at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.
A special word about obesity: A Framingham Heart Study analysis concluded that, after controlling for other cardiovascular risk factors, obese individuals had double the risk of new-onset heart failure, compared with normal weight subjects, during a mean follow-up of 14 years. For each one-unit increase in body mass index, the adjusted risk of heart failure climbed by 5% in men and 7% in women (N Engl J Med. 2002 Aug 1;347[5]:305-13). And that spells trouble down the line.
“You can imagine, with the marked increase in overweight and obesity status now affecting over half of U.S. adults, what this will mean for a potential rise in heart failure prevalence and incidence unless we do something further to modify this,” the cardiologist observed.
Dr. Fonarow is a member of the writing group for the ACC/AHA guidelines on management of heart failure. They recommend as a risk reduction strategy identification of patients with stage A pre–heart failure and addressing their risk factors: treating their hypertension and lipid disorders, gaining control over metabolic syndrome, discouraging heavy alcohol intake, and encouraging smoking cessation and regular exercise (J Am Coll Cardiol. 2013 Oct 15;62[16]:e147-239).
What kind of reduction in heart failure risk can be expected via these measures?
Antihypertensive therapy
More than a quarter century ago, the landmark SHEP trial (Systolic Hypertension in the Elderly Program) in more than 4,700 hypertensive seniors showed that treatment with diuretics and beta-blockers resulted in a 49% reduction in heart failure events, compared with placebo. And this has been a consistent finding in other studies: A meta-analysis of all 12 major randomized trials of antihypertensive therapy conducted over a 20-year period showed that treatment resulted in a whopping 52% reduction in the risk of heart failure (J Am Coll Cardiol. 1995 Apr; 27[5]:1214-8).
“If you ask most people why they’re on antihypertensive medication, they say, ‘Oh, to prevent heart attacks and stroke.’ But in fact the greatest relative risk reduction that we see is this remarkable reduction in the risk of developing heart failure with blood pressure treatment,” Dr. Fonarow said.
There has been some argument within medicine as to whether aggressive blood pressure lowering is appropriate in individuals over age 80. But in the HYVET trial (Hypertension in the Very Elderly Trial) conducted in that age group, the use of diuretics and/or ACE inhibitors to lower systolic blood pressure from roughly 155 mm Hg to 145 mm Hg resulted in a dramatic 64% reduction in the rate of new-onset heart failure (N Engl J Med. 2008 May 1;358[18]:1887-98).
How low to go with blood pressure reduction in order to maximize the heart failure risk reduction benefit? In the SPRINT trial (Systolic Blood Pressure Intervention Trial) of 9,361 hypertensive patients with a history of cardiovascular disease or multiple risk factors, participants randomized to a goal of less than 120 mm Hg enjoyed a 38% lower risk of heart failure events, compared with those whose target was less than 140 mm Hg (N Engl J Med. 2015 Nov 26;373[22]:2103-16).
A secondary analysis from SPRINT showed that the risk of acute decompensated heart failure was 37% lower in patients treated to the target of less than 120 mm Hg. That finding takes on particular importance because SPRINT participants who developed acute decompensated heart failure had a 27-fold increase in cardiovascular death (Circ Heart Fail. 2017 Apr; doi: 10.1161/CIRCHEARTFAILURE.116.003613).
Lipid lowering
A meta-analysis of four major, randomized clinical trials of intensive versus moderate statin therapy in 27,546 patients with stable coronary artery disease or acute coronary syndrome concluded that intensive therapy resulted in a 27% reduction in the risk of hospitalization for heart failure (J Am Coll Cardiol. 2006 Jun 6;47[11]:2326-31).
SGLT-2 inhibition
Until the randomized EMPA-REG OUTCOME trial of the sodium-glucose transporter 2 (SGLT-2) inhibitor empagliflozin(Jardiance), no glucose-lowering drug available for treatment of type 2 diabetes had shown any benefit in terms of reducing diabetic patients’ elevated risk of heart failure. Neither had weight loss. Abundant evidence showed that glycemic control had no impact on the risk of heart failure events. So EMPA-REG OUTCOME was cause for celebration among heart failure specialists, with its demonstration of a 35% reduction in the risk of hospitalization for heart failure, compared with placebo in more than 7,000 randomized patients. The risk of death because of heart failure was chopped by 68%. Sharp reductions in other cardiovascular events were also seen with empagliflozin (N Engl J Med. 2015 Nov 26;373[22]:2117-28).
Similar benefits were subsequently documented with another SGLT-2 inhibitor, canagliflozin(Invokana), in the CANVAS study program (N Engl J Med. 2017 Aug 17;377:644-57).
The reduction in cardiovascular mortality achieved with empagliflozin in EMPA-REG OUTCOME was actually bigger than seen with ACE inhibitors and angiotensin-receptor blockers (ARBs) in earlier landmark heart failure trials (Eur J Heart Fail. 2017 Jan;19[1]:43-53).
Dr. Fonarow views these data as “compelling.” These trials mark a huge step forward in the prevention of heart failure.
“We now for the first time in patients with diabetes have the ability to markedly prevent heart failure as well as cardiovascular death,” the cardiologist commented. “It is critical for cardiologists and heart failure specialists to play an active role in this [pharmacologic diabetes] management, as choice of therapy is a key determinant of outcomes, including survival.”
ACE inhibitors and ARBs
The ACC/AHA heart failure guidelines give a Class I recommendation to the routine use of ACE inhibitors or ARBs in patients at high risk for developing heart failure because of a history of diabetes, hypertension with associated cardiovascular risk factors, or any form of atherosclerotic vascular disease.
Lifestyle modification
Heavy drinking is known to raise the risk of heart failure. However, moderate alcohol consumption may be protective. In a classic prospective cohort study, individuals who reported consuming 1.5-4 drinks per day in the previous month had a 47% reduction in subsequent new-onset heart failure, compared with teetotalers in a multivariate analysis adjusted for conventional cardiovascular risk factors. Those who drank less than 1.5 drinks per day had a 21% reduction in heart failure risk, compared with the nondrinkers (JAMA. 2001 Apr 18;285[15]:1971-7).
In the prospective observational Physicians’ Health Study of nearly 21,000 men, adherence to six modifiable healthy lifestyle factors was associated with an incremental stepwise reduction in lifetime risk of developing heart failure. The six lifestyle factors – a forerunner of the AHA’s Life’s Simple 7 – were maintaining a normal body weight, stopping smoking, getting exercise, drinking alcohol in moderation, consuming breakfast cereals, and eating fruits and vegetables. Male physicians who shunned all six had a 21.2% lifetime risk of heart failure; those who followed at least four of the healthy lifestyle factors had a 10.1% risk (JAMA 2009 Jul 22;302[4]:394-400).
In a separate analysis from the Physicians’ Health Study, men who engaged in vigorous exercise to the point of breaking a sweat as little as one to three times per month had an 18% lower risk of developing heart failure during follow-up, compared with inactive men (Circulation 2009 Jan 6;119[1]:44-52).
What’s next in prevention of heart failure
Heart failure is one of the most expensive health care problems in the United States, and one of the deadliest. Today an estimated 6.5 million Americans have symptomatic heart failure. But that’s just the tip of the iceberg.
“Countless millions more are likely to manifest heart failure in the future,” Dr. Fonarow warned, noting the vast prevalence of identifiable risk factors.
It’s time for a high-visibility public health campaign designed to foster community education and engagement regarding heart failure prevention, he added.
“We have a lot of action and events around preventing atherosclerotic cardiovascular disease. But can you think of any campaign you’ve seen focusing specifically on heart failure? Heart failure isn’t one of the endpoints in the ACC/AHA Atherosclerotic Cardiovascular Disease Risk Calculator or even the new hypertension risk calculator, so we need to take this a whole lot more seriously,” the cardiologist said.
The 2017 focused update of the ACC/AHA heart failure guidelines endorsed a novel strategy of primary care–centered, biomarker-based screening of patients with cardiovascular risk factors as a means of triggering early intervention to prevent heart failure (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803). This strategy, which received a Class IIa recommendation, involves screening measurement of a natriuretic peptide biomarker.
The recommendation was based on evidence including the STOP-HF randomized trial (St. Vincent’s Screening to Prevent Heart Failure Study), in which 1,374 asymptomatic Irish patients with cardiovascular risk factors were randomized to routine primary care or primary care plus screening with brain-type natriuretic peptide testing. Patients with a brain-type natriuretic peptide level of 50 pg/mL or more were directed to team-based care involving a collaboration between their primary care physician and a specialist cardiovascular service focused on optimizing guideline-directed medical therapy. During a mean follow-up of 4.2 years, the primary endpoint of new-onset left ventricular dysfunction occurred in 5.3% of the intervention group and 8.7% of controls, for a 45% relative risk reduction (JAMA 2013 Jul 3;310[1]:66-74).
Dr. Fonarow reported receiving research grants from and serving as a consultant to the National Heart, Lung, and Blood Institute and a handful of medical companies.
EXPERT ANALYSIS FROM THE ANNUAL CARDIOVASCULAR CONFERENCE AT SNOWMASS
STEMI success stagnating
SNOWMASS, COLO. – , Ajay J. Kirtane, MD, declared at the Annual Cardiovascular Conference at Snowmass.
“We have to recognize the fact that our success has somewhat plateaued. We’ve made great strides in shortening door-to-balloon times, but further reductions in [that measure] are not translating into further reductions in adverse outcomes,” observed Dr. Kirtane of Columbia University, New York.
He and others have identified a number of reasons why ST-elevation myocardial infarction (STEMI) mortality has flattened. One is the continued protracted lag time from symptom onset to arrival at the emergency department. Progress here will require effective public education programs.
“By the time patients are getting to the cath lab, we’re sort of running out of time to salvage the myocardium,” Dr. Kirtane said. “We need to get people to the lab really, really quickly and recognize that symptom onset is still an area in need of improvement.”
The greatest limitation of primary percutaneous coronary intervention (PCI) for treatment of STEMI, however, is poor recovery of left ventricular function. As STEMI mortality has fallen over the years, rates of heart failure caused by suboptimal salvage of myocardium have climbed. Only about two-thirds of patients undergoing primary PCI obtain successful reperfusion; that’s in part due to distal embolization, a problem that hasn’t yet been solved.
One hope for improved reperfusion success that has been dashed is aspiration thrombectomy. It was an attractive concept, but optical coherence imaging has shown that after aspiration, there is still a good deal of thrombus remaining in the vessel. And large randomized trials failed to show a reduction in ischemic events. Thus, the current American College of Cardiology/American Heart Association STEMI guidelines give routine aspiration thrombectomy before primary PCI a class III rating, meaning don’t do it (J Am Coll Cardiol. 2013 Jan. doi: 10.1016/j.jacc.2012.11.019).
What about nonculprit lesions?
A hot topic in STEMI management is what to do about residual disease in nonculprit vessels after primary PCI.
“Some people have drawn upon trials like COURAGE to inform their decision making, saying ‘Now the patient is stabilized, we’ve treated the STEMI, so we could now treat the patient like a COURAGE patient [with optimal medical therapy alone].’ I would caution against extrapolating the results of COURAGE and other stable ischemic heart disease paradigms to these types of patients. They’ve already presented with a very high risk feature – STEMI – and in addition, in the COURAGE trial there were only 118 patients that had acute coronary syndrome of less than 2 weeks’ duration out of more than 2,000 subjects,” Dr. Kirtane said.
“Intravascular ultrasound studies show that nonculprit plaques in stable angina are very different from those in STEMI: They’re typically fibrotic and stable, while even the nonculprit plaques in STEMI or non-STEMI ACS are much more inflamed and vulnerable,” he added.
He predicted clarity regarding best management in this area will come from the ongoing COMPLETE trial, a multinational study of nearly 4,000 patients randomized to staged nonculprit lesion PCI versus medical therapy plus culprit lesion-only revascularization. The study is due to be completed late in 2018.
Improving pharmacotherapy
Rates of hospital discharge on guideline-directed optimal medical therapy after primary PCI have risen steadily in recent years. However, studies indicate a significant minority of patients drop from dual-antiplatelet therapy to aspirin alone within a month after leaving the hospital.
Also, it’s essential to effectively inhibit both platelets and thrombus in the catheterization lab. But is that happening consistently? There is now evidence of delayed absorption of the potent oral antiplatelet agents in STEMI patients. Moreover, that delay is exacerbated by having morphine or fentanyl on board.
“It’s been shown that even with ticagrelor and prasugrel, in STEMI patients at 2 hours, you still don’t have sufficient inhibition of platelet aggregation, whereas if I gave one of those drugs to any of us here in the audience now we’d have full effect within an hour or 2 max. That’s one of the reasons why there’s a rationale for using an intravenous agent such as cangrelor [Kengreal], a nonthienopyridine direct P2Y12 inhibitor,” Dr. Kirtane said.
Transradial access for primary PCI
Dr. Kirtane argued in a recent editorial that widespread adoption of transradial PCI for STEMI will provide the next major advance in STEMI systems of care resulting in improved clinical outcomes (JAMA Cardiol. 2017 Oct 1;2[10]:1057-8).
This is a controversial issue, he acknowledged. “There are interventional cardiologists who say, ‘No way.’ ” But studies indicate that transradial PCI for STEMI reduces mortality by 16%-48% compared with transfemoral access, without a significant cost in terms of door-to-balloon time. For now, transfemoral access PCI remains the most common strategy for STEMI patients in the United States, although the use of transradial primary PCI is growing.
Dr. Kirtane reported receiving research grants from more than half a dozen medical device companies.
SNOWMASS, COLO. – , Ajay J. Kirtane, MD, declared at the Annual Cardiovascular Conference at Snowmass.
“We have to recognize the fact that our success has somewhat plateaued. We’ve made great strides in shortening door-to-balloon times, but further reductions in [that measure] are not translating into further reductions in adverse outcomes,” observed Dr. Kirtane of Columbia University, New York.
He and others have identified a number of reasons why ST-elevation myocardial infarction (STEMI) mortality has flattened. One is the continued protracted lag time from symptom onset to arrival at the emergency department. Progress here will require effective public education programs.
“By the time patients are getting to the cath lab, we’re sort of running out of time to salvage the myocardium,” Dr. Kirtane said. “We need to get people to the lab really, really quickly and recognize that symptom onset is still an area in need of improvement.”
The greatest limitation of primary percutaneous coronary intervention (PCI) for treatment of STEMI, however, is poor recovery of left ventricular function. As STEMI mortality has fallen over the years, rates of heart failure caused by suboptimal salvage of myocardium have climbed. Only about two-thirds of patients undergoing primary PCI obtain successful reperfusion; that’s in part due to distal embolization, a problem that hasn’t yet been solved.
One hope for improved reperfusion success that has been dashed is aspiration thrombectomy. It was an attractive concept, but optical coherence imaging has shown that after aspiration, there is still a good deal of thrombus remaining in the vessel. And large randomized trials failed to show a reduction in ischemic events. Thus, the current American College of Cardiology/American Heart Association STEMI guidelines give routine aspiration thrombectomy before primary PCI a class III rating, meaning don’t do it (J Am Coll Cardiol. 2013 Jan. doi: 10.1016/j.jacc.2012.11.019).
What about nonculprit lesions?
A hot topic in STEMI management is what to do about residual disease in nonculprit vessels after primary PCI.
“Some people have drawn upon trials like COURAGE to inform their decision making, saying ‘Now the patient is stabilized, we’ve treated the STEMI, so we could now treat the patient like a COURAGE patient [with optimal medical therapy alone].’ I would caution against extrapolating the results of COURAGE and other stable ischemic heart disease paradigms to these types of patients. They’ve already presented with a very high risk feature – STEMI – and in addition, in the COURAGE trial there were only 118 patients that had acute coronary syndrome of less than 2 weeks’ duration out of more than 2,000 subjects,” Dr. Kirtane said.
“Intravascular ultrasound studies show that nonculprit plaques in stable angina are very different from those in STEMI: They’re typically fibrotic and stable, while even the nonculprit plaques in STEMI or non-STEMI ACS are much more inflamed and vulnerable,” he added.
He predicted clarity regarding best management in this area will come from the ongoing COMPLETE trial, a multinational study of nearly 4,000 patients randomized to staged nonculprit lesion PCI versus medical therapy plus culprit lesion-only revascularization. The study is due to be completed late in 2018.
Improving pharmacotherapy
Rates of hospital discharge on guideline-directed optimal medical therapy after primary PCI have risen steadily in recent years. However, studies indicate a significant minority of patients drop from dual-antiplatelet therapy to aspirin alone within a month after leaving the hospital.
Also, it’s essential to effectively inhibit both platelets and thrombus in the catheterization lab. But is that happening consistently? There is now evidence of delayed absorption of the potent oral antiplatelet agents in STEMI patients. Moreover, that delay is exacerbated by having morphine or fentanyl on board.
“It’s been shown that even with ticagrelor and prasugrel, in STEMI patients at 2 hours, you still don’t have sufficient inhibition of platelet aggregation, whereas if I gave one of those drugs to any of us here in the audience now we’d have full effect within an hour or 2 max. That’s one of the reasons why there’s a rationale for using an intravenous agent such as cangrelor [Kengreal], a nonthienopyridine direct P2Y12 inhibitor,” Dr. Kirtane said.
Transradial access for primary PCI
Dr. Kirtane argued in a recent editorial that widespread adoption of transradial PCI for STEMI will provide the next major advance in STEMI systems of care resulting in improved clinical outcomes (JAMA Cardiol. 2017 Oct 1;2[10]:1057-8).
This is a controversial issue, he acknowledged. “There are interventional cardiologists who say, ‘No way.’ ” But studies indicate that transradial PCI for STEMI reduces mortality by 16%-48% compared with transfemoral access, without a significant cost in terms of door-to-balloon time. For now, transfemoral access PCI remains the most common strategy for STEMI patients in the United States, although the use of transradial primary PCI is growing.
Dr. Kirtane reported receiving research grants from more than half a dozen medical device companies.
SNOWMASS, COLO. – , Ajay J. Kirtane, MD, declared at the Annual Cardiovascular Conference at Snowmass.
“We have to recognize the fact that our success has somewhat plateaued. We’ve made great strides in shortening door-to-balloon times, but further reductions in [that measure] are not translating into further reductions in adverse outcomes,” observed Dr. Kirtane of Columbia University, New York.
He and others have identified a number of reasons why ST-elevation myocardial infarction (STEMI) mortality has flattened. One is the continued protracted lag time from symptom onset to arrival at the emergency department. Progress here will require effective public education programs.
“By the time patients are getting to the cath lab, we’re sort of running out of time to salvage the myocardium,” Dr. Kirtane said. “We need to get people to the lab really, really quickly and recognize that symptom onset is still an area in need of improvement.”
The greatest limitation of primary percutaneous coronary intervention (PCI) for treatment of STEMI, however, is poor recovery of left ventricular function. As STEMI mortality has fallen over the years, rates of heart failure caused by suboptimal salvage of myocardium have climbed. Only about two-thirds of patients undergoing primary PCI obtain successful reperfusion; that’s in part due to distal embolization, a problem that hasn’t yet been solved.
One hope for improved reperfusion success that has been dashed is aspiration thrombectomy. It was an attractive concept, but optical coherence imaging has shown that after aspiration, there is still a good deal of thrombus remaining in the vessel. And large randomized trials failed to show a reduction in ischemic events. Thus, the current American College of Cardiology/American Heart Association STEMI guidelines give routine aspiration thrombectomy before primary PCI a class III rating, meaning don’t do it (J Am Coll Cardiol. 2013 Jan. doi: 10.1016/j.jacc.2012.11.019).
What about nonculprit lesions?
A hot topic in STEMI management is what to do about residual disease in nonculprit vessels after primary PCI.
“Some people have drawn upon trials like COURAGE to inform their decision making, saying ‘Now the patient is stabilized, we’ve treated the STEMI, so we could now treat the patient like a COURAGE patient [with optimal medical therapy alone].’ I would caution against extrapolating the results of COURAGE and other stable ischemic heart disease paradigms to these types of patients. They’ve already presented with a very high risk feature – STEMI – and in addition, in the COURAGE trial there were only 118 patients that had acute coronary syndrome of less than 2 weeks’ duration out of more than 2,000 subjects,” Dr. Kirtane said.
“Intravascular ultrasound studies show that nonculprit plaques in stable angina are very different from those in STEMI: They’re typically fibrotic and stable, while even the nonculprit plaques in STEMI or non-STEMI ACS are much more inflamed and vulnerable,” he added.
He predicted clarity regarding best management in this area will come from the ongoing COMPLETE trial, a multinational study of nearly 4,000 patients randomized to staged nonculprit lesion PCI versus medical therapy plus culprit lesion-only revascularization. The study is due to be completed late in 2018.
Improving pharmacotherapy
Rates of hospital discharge on guideline-directed optimal medical therapy after primary PCI have risen steadily in recent years. However, studies indicate a significant minority of patients drop from dual-antiplatelet therapy to aspirin alone within a month after leaving the hospital.
Also, it’s essential to effectively inhibit both platelets and thrombus in the catheterization lab. But is that happening consistently? There is now evidence of delayed absorption of the potent oral antiplatelet agents in STEMI patients. Moreover, that delay is exacerbated by having morphine or fentanyl on board.
“It’s been shown that even with ticagrelor and prasugrel, in STEMI patients at 2 hours, you still don’t have sufficient inhibition of platelet aggregation, whereas if I gave one of those drugs to any of us here in the audience now we’d have full effect within an hour or 2 max. That’s one of the reasons why there’s a rationale for using an intravenous agent such as cangrelor [Kengreal], a nonthienopyridine direct P2Y12 inhibitor,” Dr. Kirtane said.
Transradial access for primary PCI
Dr. Kirtane argued in a recent editorial that widespread adoption of transradial PCI for STEMI will provide the next major advance in STEMI systems of care resulting in improved clinical outcomes (JAMA Cardiol. 2017 Oct 1;2[10]:1057-8).
This is a controversial issue, he acknowledged. “There are interventional cardiologists who say, ‘No way.’ ” But studies indicate that transradial PCI for STEMI reduces mortality by 16%-48% compared with transfemoral access, without a significant cost in terms of door-to-balloon time. For now, transfemoral access PCI remains the most common strategy for STEMI patients in the United States, although the use of transradial primary PCI is growing.
Dr. Kirtane reported receiving research grants from more than half a dozen medical device companies.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
The shrinking role of surgical aortic valve replacement
SNOWMASS, COLO. – Michael J. Mack, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
That’s assuming, hypothetically, that two ongoing randomized trials – PARTNER 3 and EVOLUT R – comparing TAVR (transcatheter aortic valve replacement) and SAVR (surgical aortic valve replacement) in low-surgical-risk patients have positive results. If so, TAVR will be proven noninferior to SAVR, as has already been convincingly shown in randomized trials conducted in high- and intermediate-surgical-risk patients.
Several factors are working against universal adoption of TAVR. There are unresolved concerns about TAVR’s durability, its issues with valve thrombosis, and its greater need for new pacemaker implantation relative to SAVR. Those questions are among the issues being addressed in nearly two dozen ongoing or upcoming TAVR trials, said Dr. Mack, director of the cardiovascular service line at Baylor Scott & White Health System, Houston.
Here are the patients Dr. Mack predicts will likely stick with SAVR for the foreseeable future:
- Younger patients. Many younger, low-surgical-risk patients will be concerned about TAVR valves’ durability and the current higher pacemaker rate.
“We have some idea of what durability is in the surgical population. What we usually quote is 12-15 years. There has been no major signal of early valve deterioration in TAVR, but there aren’t yet a significant number of patients alive for more than 5 years. Be that as it may, no significant concerns yet, but the other shoe hasn’t dropped,” the cardiothoracic surgeon observed.
Both PARTNER 3 and the EVOLUT R low-risk trial will follow participants annually for 10 years, eventually providing a robust, combined 2,000-patient database to assess comparative device durability.
The 30-day rates of permanent pacemaker implantation in TAVR recipients without a preexisting pacemaker is in the 12%-16% range with the newer-generation Evolut R and Sapien 3 valves. The indication is often new-onset left bundle branch block or complete heart block.
“I don’t think the increased pacemaker incidence is a huge problem now, but with the younger population I think it’s going to be more of an issue,” according to Dr. Mack. “It’s one thing to need a pacemaker if you’re 80-85 years old, but it’s totally different in somebody who’s 55 or 65 that has 30-35 years to live. Pacemaker leads are not benign in that population.”
“On the other hand, there is a thought that younger patients have less intrinsic conduction system disease. It may be that they are less prone to needing a new pacemaker afterward,” he added.
TAVR valve leaflet thrombosis is a concern. While a change in transvalvular gradient on echocardiography provides a signal for this complication, the actual diagnosis of valve thrombosis requires four-dimensional CT. Much better data on the true incidence and clinical ramifications of valve thrombosis in both TAVR and SAVR are coming. For example, the PARTNER 3 and EVOLUT R LR trials will each include 400-patient substudies with four-dimensional CT aimed at answering questions about valve thrombosis. The GALILEO trial, involving 1,520 TAVR patients, is designed to determine whether low-dose rivaroxaban prevents valve thrombosis and periprocedural embolization. Results of this randomized trial are due in about a year. Similarly, the 1,509-patient randomized ATLANTIS trial is looking at the effects of apixaban versus warfarin versus dual or single antiplatelet therapy.
If long-term anticoagulation in TAVR patients is found to be beneficial, that may steer some patients toward SAVR, especially if they are physically active or at high bleeding risk.
- Aortic stenosis patients with a high Syntax score and multivessel coronary artery disease. This group is best served by concomitant SAVR and coronary artery bypass grafting surgery.
- Patients with low or intermediate surgical risk with multivalve disease. “We know that patients with moderate to severe mitral regurgitation and/or moderate to severe tricuspid regurgitation do not do well after TAVR,” the surgeon said.
- Rheumatic valve disease patients.
- Patients who present at a site that offers SAVR only. “There are about 1,150 cardiac surgery programs in the United States and about 560 TAVR programs. There is concern that patients who don’t come in to a center that offers TAVR will not be offered TAVR as an option. I think there’s probably some truth to that,” Dr. Mack said.
- Patients going to sites without a well-functioning collaborative heart team. “In institutions where surgeons and cardiologists don’t get along, turf is much more of an issue, and surgeons are going to hold on to those patients more closely,” he observed.
- Patient’s with certain preferences. “All other things being equal, the patient is always going to choose the less invasive option. However, we do see some patients – I think it’s about 1 out of 10 – who express a preference to stay with the tried and true surgery,” according to Dr. Mack.
He reported receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.
SNOWMASS, COLO. – Michael J. Mack, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
That’s assuming, hypothetically, that two ongoing randomized trials – PARTNER 3 and EVOLUT R – comparing TAVR (transcatheter aortic valve replacement) and SAVR (surgical aortic valve replacement) in low-surgical-risk patients have positive results. If so, TAVR will be proven noninferior to SAVR, as has already been convincingly shown in randomized trials conducted in high- and intermediate-surgical-risk patients.
Several factors are working against universal adoption of TAVR. There are unresolved concerns about TAVR’s durability, its issues with valve thrombosis, and its greater need for new pacemaker implantation relative to SAVR. Those questions are among the issues being addressed in nearly two dozen ongoing or upcoming TAVR trials, said Dr. Mack, director of the cardiovascular service line at Baylor Scott & White Health System, Houston.
Here are the patients Dr. Mack predicts will likely stick with SAVR for the foreseeable future:
- Younger patients. Many younger, low-surgical-risk patients will be concerned about TAVR valves’ durability and the current higher pacemaker rate.
“We have some idea of what durability is in the surgical population. What we usually quote is 12-15 years. There has been no major signal of early valve deterioration in TAVR, but there aren’t yet a significant number of patients alive for more than 5 years. Be that as it may, no significant concerns yet, but the other shoe hasn’t dropped,” the cardiothoracic surgeon observed.
Both PARTNER 3 and the EVOLUT R low-risk trial will follow participants annually for 10 years, eventually providing a robust, combined 2,000-patient database to assess comparative device durability.
The 30-day rates of permanent pacemaker implantation in TAVR recipients without a preexisting pacemaker is in the 12%-16% range with the newer-generation Evolut R and Sapien 3 valves. The indication is often new-onset left bundle branch block or complete heart block.
“I don’t think the increased pacemaker incidence is a huge problem now, but with the younger population I think it’s going to be more of an issue,” according to Dr. Mack. “It’s one thing to need a pacemaker if you’re 80-85 years old, but it’s totally different in somebody who’s 55 or 65 that has 30-35 years to live. Pacemaker leads are not benign in that population.”
“On the other hand, there is a thought that younger patients have less intrinsic conduction system disease. It may be that they are less prone to needing a new pacemaker afterward,” he added.
TAVR valve leaflet thrombosis is a concern. While a change in transvalvular gradient on echocardiography provides a signal for this complication, the actual diagnosis of valve thrombosis requires four-dimensional CT. Much better data on the true incidence and clinical ramifications of valve thrombosis in both TAVR and SAVR are coming. For example, the PARTNER 3 and EVOLUT R LR trials will each include 400-patient substudies with four-dimensional CT aimed at answering questions about valve thrombosis. The GALILEO trial, involving 1,520 TAVR patients, is designed to determine whether low-dose rivaroxaban prevents valve thrombosis and periprocedural embolization. Results of this randomized trial are due in about a year. Similarly, the 1,509-patient randomized ATLANTIS trial is looking at the effects of apixaban versus warfarin versus dual or single antiplatelet therapy.
If long-term anticoagulation in TAVR patients is found to be beneficial, that may steer some patients toward SAVR, especially if they are physically active or at high bleeding risk.
- Aortic stenosis patients with a high Syntax score and multivessel coronary artery disease. This group is best served by concomitant SAVR and coronary artery bypass grafting surgery.
- Patients with low or intermediate surgical risk with multivalve disease. “We know that patients with moderate to severe mitral regurgitation and/or moderate to severe tricuspid regurgitation do not do well after TAVR,” the surgeon said.
- Rheumatic valve disease patients.
- Patients who present at a site that offers SAVR only. “There are about 1,150 cardiac surgery programs in the United States and about 560 TAVR programs. There is concern that patients who don’t come in to a center that offers TAVR will not be offered TAVR as an option. I think there’s probably some truth to that,” Dr. Mack said.
- Patients going to sites without a well-functioning collaborative heart team. “In institutions where surgeons and cardiologists don’t get along, turf is much more of an issue, and surgeons are going to hold on to those patients more closely,” he observed.
- Patient’s with certain preferences. “All other things being equal, the patient is always going to choose the less invasive option. However, we do see some patients – I think it’s about 1 out of 10 – who express a preference to stay with the tried and true surgery,” according to Dr. Mack.
He reported receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.
SNOWMASS, COLO. – Michael J. Mack, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
That’s assuming, hypothetically, that two ongoing randomized trials – PARTNER 3 and EVOLUT R – comparing TAVR (transcatheter aortic valve replacement) and SAVR (surgical aortic valve replacement) in low-surgical-risk patients have positive results. If so, TAVR will be proven noninferior to SAVR, as has already been convincingly shown in randomized trials conducted in high- and intermediate-surgical-risk patients.
Several factors are working against universal adoption of TAVR. There are unresolved concerns about TAVR’s durability, its issues with valve thrombosis, and its greater need for new pacemaker implantation relative to SAVR. Those questions are among the issues being addressed in nearly two dozen ongoing or upcoming TAVR trials, said Dr. Mack, director of the cardiovascular service line at Baylor Scott & White Health System, Houston.
Here are the patients Dr. Mack predicts will likely stick with SAVR for the foreseeable future:
- Younger patients. Many younger, low-surgical-risk patients will be concerned about TAVR valves’ durability and the current higher pacemaker rate.
“We have some idea of what durability is in the surgical population. What we usually quote is 12-15 years. There has been no major signal of early valve deterioration in TAVR, but there aren’t yet a significant number of patients alive for more than 5 years. Be that as it may, no significant concerns yet, but the other shoe hasn’t dropped,” the cardiothoracic surgeon observed.
Both PARTNER 3 and the EVOLUT R low-risk trial will follow participants annually for 10 years, eventually providing a robust, combined 2,000-patient database to assess comparative device durability.
The 30-day rates of permanent pacemaker implantation in TAVR recipients without a preexisting pacemaker is in the 12%-16% range with the newer-generation Evolut R and Sapien 3 valves. The indication is often new-onset left bundle branch block or complete heart block.
“I don’t think the increased pacemaker incidence is a huge problem now, but with the younger population I think it’s going to be more of an issue,” according to Dr. Mack. “It’s one thing to need a pacemaker if you’re 80-85 years old, but it’s totally different in somebody who’s 55 or 65 that has 30-35 years to live. Pacemaker leads are not benign in that population.”
“On the other hand, there is a thought that younger patients have less intrinsic conduction system disease. It may be that they are less prone to needing a new pacemaker afterward,” he added.
TAVR valve leaflet thrombosis is a concern. While a change in transvalvular gradient on echocardiography provides a signal for this complication, the actual diagnosis of valve thrombosis requires four-dimensional CT. Much better data on the true incidence and clinical ramifications of valve thrombosis in both TAVR and SAVR are coming. For example, the PARTNER 3 and EVOLUT R LR trials will each include 400-patient substudies with four-dimensional CT aimed at answering questions about valve thrombosis. The GALILEO trial, involving 1,520 TAVR patients, is designed to determine whether low-dose rivaroxaban prevents valve thrombosis and periprocedural embolization. Results of this randomized trial are due in about a year. Similarly, the 1,509-patient randomized ATLANTIS trial is looking at the effects of apixaban versus warfarin versus dual or single antiplatelet therapy.
If long-term anticoagulation in TAVR patients is found to be beneficial, that may steer some patients toward SAVR, especially if they are physically active or at high bleeding risk.
- Aortic stenosis patients with a high Syntax score and multivessel coronary artery disease. This group is best served by concomitant SAVR and coronary artery bypass grafting surgery.
- Patients with low or intermediate surgical risk with multivalve disease. “We know that patients with moderate to severe mitral regurgitation and/or moderate to severe tricuspid regurgitation do not do well after TAVR,” the surgeon said.
- Rheumatic valve disease patients.
- Patients who present at a site that offers SAVR only. “There are about 1,150 cardiac surgery programs in the United States and about 560 TAVR programs. There is concern that patients who don’t come in to a center that offers TAVR will not be offered TAVR as an option. I think there’s probably some truth to that,” Dr. Mack said.
- Patients going to sites without a well-functioning collaborative heart team. “In institutions where surgeons and cardiologists don’t get along, turf is much more of an issue, and surgeons are going to hold on to those patients more closely,” he observed.
- Patient’s with certain preferences. “All other things being equal, the patient is always going to choose the less invasive option. However, we do see some patients – I think it’s about 1 out of 10 – who express a preference to stay with the tried and true surgery,” according to Dr. Mack.
He reported receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Fight statin phobia with hard facts
SNOWMASS, COLO. – One of the toughest tasks in all of preventive cardiology is to convince statin-phobic patients at increased cardiovascular risk that they should take a statin, Robert A. Vogel, MD, observed.
“The two hardest challenges I have in my practice are getting people to stop smoking and getting people who have fear of statins to take statins. That’s half my practice. ,” declared Dr. Vogel, a cardiologist at the University of Colorado, Denver.
“There is one true harm of a statin that I always worry about, and that’s hemorrhagic stroke. It’s rare, but it does occur,” the cardiologist said at the Annual Cardiovascular Conference at Snowmass.
Dr. Vogel highlighted key studies that he believes have convincingly addressed impaired cognition and other proposed statin side effects. He also provided an update on the safety profile of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.
Neurocognitive problems: The Food and Drug Administration really ratcheted up patient fretting when it mandated in 2012 that the labeling for all statins must include a warning of postmarketing reports of adverse events involving ill-defined memory impairment and confusion that were reversed upon drug discontinuation.
“I can tell you, I’ve had dozens of patients come in and say, ‘What about this warning? I’m afraid of dementia,’ ” Dr. Vogel said.
It’s tough to refute anecdotal case reports, but Dr. Vogel pointed to several published meta-analyses of prospective cohort studies, randomized controlled trials, and cross-sectional studies to illustrate his point. For example, investigators at Johns Hopkins University in Baltimore analyzed the results of 16 high-quality randomized trials and prospective cohort studies and found that the short-term studies showed no effect of statin therapy on measurable cognitive endpoints. Moreover, the pooled results of eight long-term studies, including more than 23,000 patients, showed a significant 29% reduction in new-onset dementia in statin-treated patients (Mayo Clin Proc. 2013 Nov;88[11]1213-21).
Another meta-analysis, this one including 27 studies, concluded there is “moderate-quality evidence” to suggest statin users have no increased incidence of dementia, mild cognitive impairment, or any change in neurocognitive scores related to executive function, declarative memory, processing speed, or global cognitive performance.
In this same report, the investigators delved into the FDA’s adverse event reporting database and determined that the rate of reported cognitive-related adverse events was 1.9 cases per 1 million statin prescriptions, identical to the rate for clopidogrel and essentially the same as the 1.6 cases per 1 million rate for losartan (Ann Intern Med. 2013 Nov 19;159[10]:688-97).
“It shows that if you take any drug and put it in the type of population we give these drugs to, you’re going to see about the same frequency of these anecdotal reports, with no signal that statins are any worse than any other drugs we use in cardiology. Is this proof that statins don’t cause cognitive impairment? No, but it’s suggestive that if you give drugs, people have adverse events that may or may not be related to those drugs. So this was reassuring to me that we’ll see this stuff anecdotally, but it probably isn’t due to the statin itself,” Dr. Vogel continued.
Myalgia: In the STOMP study (Effect of Statins on Skeletal Muscle Function and Performance), investigators at Hartford (Conn.) Hospital randomized 420 healthy, statin-naive subjects in a double-blind fashion to 80 mg/day of atorvastatin or placebo for 6 months. The incidence of myalgia was 9.4% in the atorvastatin group compared with 4.6% in placebo-treated controls. Of note, muscle strength on formal testing wasn’t reduced to a greater extent in myalgic patients on atorvastatin than in myalgic patients on placebo (Circulation. 2013 Jan 1;127[1]:96-103).
“There is a signal there,” Dr. Vogel commented. “So the true [placebo-subtracted] incidence of myalgias on a high-dose statin is about 5%. It’s not 20%, it’s not 30%, it’s about 1 patient in 20. It’s real, but it’s not everybody. Those are the numbers you have to think about. If half your patients on statin therapy are getting myalgias, you need to go into a different practice because you’ve got a bunch of Web-searching patients.”
Diabetes: A meta-analysis of 13 randomized controlled trials of statins with more than 91,000 participants and a mean of 4 years of follow-up concluded that for every 255 patients treated with a statin for 4 years, there would be one extra case of new-onset type 2 diabetes, a harm dwarfed by the reduction in cardiovascular events (Lancet. 2010 Feb 27;375[9716]:735-42).
The mechanism for this statin-related, slightly increased risk of developing type 2 diabetes has been clarified by a genetic analysis involving more than 223,000 participants in 43 genetic studies. A large multicenter team of investigators showed that genetic polymorphisms resulting in a less active 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene are associated with lower LDL cholesterol, slightly higher body weight and waist circumference, and increased plasma insulin and plasma glucose. The investigators showed that the more of these alleles an individual possessed, the greater the risk of type 2 diabetes (Lancet. 2015 Jan 24;385[9965]:351-61).
Hemorrhagic stroke: In the SPARCL study (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), 4,731 patients with a recent stroke or transient ischemic attack – 67% of which were ischemic strokes, 2% hemorrhagic strokes – were randomized to high-dose atorvastatin or placebo. Atorvastatin for secondary prevention markedly reduced the overall stroke risk. But this was due to a dramatic decrease in ischemic strokes. The incidence of hemorrhagic stroke was 2.3% in patients on atorvastatin at 80 mg/day for secondary prevention, compared with 1.4% in placebo-treated controls.
In multivariate analysis, the SPARCL investigators found that hemorrhagic stroke risk was increased by an adjusted 68% in patients on atorvastatin, 465% in patients whose prior stroke was hemorrhagic, and 519% in patients with a blood pressure reading of 160-179/100-109 mm Hg at their last clinic visit prior to the hemorrhagic stroke (Neurology. 2008 Jun 10;70[24 Pt 2]:2364-70).
Hepatic dysfunction: This event is extremely rare, so much so that it’s not listed as a side effect in statin labeling. Monitoring of liver function tests is no longer recommended in patients on statin therapy. If elevated tests are seen, find out about the patient’s alcohol consumption – the explanation is far more likely to lie there, according to Dr. Vogel.
What about the safety of the PCSK9 inhibitors?
Dr. Vogel is the U.S. national coordinator for the ongoing phase 3 ODYSSEY Outcomes Study, which is due to report initial results at the 2018 annual meeting of the American College of Cardiology. So far, albeit with only a couple of years worth of data in the large randomized outcome trials, the PCSK9 inhibitors haven’t been associated with muscle problems, cognitive impairment, hepatic dysfunction, or hemorrhagic stroke.
“I think we will eventually see an increased risk of hemorrhagic stroke. I don’t know why we wouldn’t because the mechanism is an antiplatelet mechanism, as with statins. But I don’t know what the incidence will be,” he said.
The EBBINGHAUS substudy of the ongoing FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) of the PCSK9 inhibitor evolocumab(Repatha) provides welcome data on cognition. EBBINGHAUS included 1,974 patients with atherosclerotic cardiovascular disease and normal cognition at baseline who underwent serial testing using the Cambridge Neuropsychological Test Automated Battery over the course of 2 years of prospective follow-up. No signal was seen of any impairment in spatial working memory, learning ability, or the elements of executive function, including planning, organization, and attention. Nor did structured assessment of patient self-reported everyday cognition differ between the active treatment and control arms. Ditto for investigators’ assessment of cognitive adverse events. Moreover, when it did occur, measurable cognitive decline proved unrelated to achieved LDL cholesterol level.
“Two-year data is not 20-year data. And cognitive decline is of great concern. Those of us in this field are going to remain vigilant and look for this, but at least for the present, when you put a patient on a PCSK9 inhibitor and see an LDL drop to 15 or 10 mg/dL – and you will see that happen – the data so far say we do not see cognitive decline,” Dr. Vogel said.
He reported serving as a paid consultant to the National Football League and receiving a research grant from and serving on the speakers bureau for Sanofi.
SNOWMASS, COLO. – One of the toughest tasks in all of preventive cardiology is to convince statin-phobic patients at increased cardiovascular risk that they should take a statin, Robert A. Vogel, MD, observed.
“The two hardest challenges I have in my practice are getting people to stop smoking and getting people who have fear of statins to take statins. That’s half my practice. ,” declared Dr. Vogel, a cardiologist at the University of Colorado, Denver.
“There is one true harm of a statin that I always worry about, and that’s hemorrhagic stroke. It’s rare, but it does occur,” the cardiologist said at the Annual Cardiovascular Conference at Snowmass.
Dr. Vogel highlighted key studies that he believes have convincingly addressed impaired cognition and other proposed statin side effects. He also provided an update on the safety profile of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.
Neurocognitive problems: The Food and Drug Administration really ratcheted up patient fretting when it mandated in 2012 that the labeling for all statins must include a warning of postmarketing reports of adverse events involving ill-defined memory impairment and confusion that were reversed upon drug discontinuation.
“I can tell you, I’ve had dozens of patients come in and say, ‘What about this warning? I’m afraid of dementia,’ ” Dr. Vogel said.
It’s tough to refute anecdotal case reports, but Dr. Vogel pointed to several published meta-analyses of prospective cohort studies, randomized controlled trials, and cross-sectional studies to illustrate his point. For example, investigators at Johns Hopkins University in Baltimore analyzed the results of 16 high-quality randomized trials and prospective cohort studies and found that the short-term studies showed no effect of statin therapy on measurable cognitive endpoints. Moreover, the pooled results of eight long-term studies, including more than 23,000 patients, showed a significant 29% reduction in new-onset dementia in statin-treated patients (Mayo Clin Proc. 2013 Nov;88[11]1213-21).
Another meta-analysis, this one including 27 studies, concluded there is “moderate-quality evidence” to suggest statin users have no increased incidence of dementia, mild cognitive impairment, or any change in neurocognitive scores related to executive function, declarative memory, processing speed, or global cognitive performance.
In this same report, the investigators delved into the FDA’s adverse event reporting database and determined that the rate of reported cognitive-related adverse events was 1.9 cases per 1 million statin prescriptions, identical to the rate for clopidogrel and essentially the same as the 1.6 cases per 1 million rate for losartan (Ann Intern Med. 2013 Nov 19;159[10]:688-97).
“It shows that if you take any drug and put it in the type of population we give these drugs to, you’re going to see about the same frequency of these anecdotal reports, with no signal that statins are any worse than any other drugs we use in cardiology. Is this proof that statins don’t cause cognitive impairment? No, but it’s suggestive that if you give drugs, people have adverse events that may or may not be related to those drugs. So this was reassuring to me that we’ll see this stuff anecdotally, but it probably isn’t due to the statin itself,” Dr. Vogel continued.
Myalgia: In the STOMP study (Effect of Statins on Skeletal Muscle Function and Performance), investigators at Hartford (Conn.) Hospital randomized 420 healthy, statin-naive subjects in a double-blind fashion to 80 mg/day of atorvastatin or placebo for 6 months. The incidence of myalgia was 9.4% in the atorvastatin group compared with 4.6% in placebo-treated controls. Of note, muscle strength on formal testing wasn’t reduced to a greater extent in myalgic patients on atorvastatin than in myalgic patients on placebo (Circulation. 2013 Jan 1;127[1]:96-103).
“There is a signal there,” Dr. Vogel commented. “So the true [placebo-subtracted] incidence of myalgias on a high-dose statin is about 5%. It’s not 20%, it’s not 30%, it’s about 1 patient in 20. It’s real, but it’s not everybody. Those are the numbers you have to think about. If half your patients on statin therapy are getting myalgias, you need to go into a different practice because you’ve got a bunch of Web-searching patients.”
Diabetes: A meta-analysis of 13 randomized controlled trials of statins with more than 91,000 participants and a mean of 4 years of follow-up concluded that for every 255 patients treated with a statin for 4 years, there would be one extra case of new-onset type 2 diabetes, a harm dwarfed by the reduction in cardiovascular events (Lancet. 2010 Feb 27;375[9716]:735-42).
The mechanism for this statin-related, slightly increased risk of developing type 2 diabetes has been clarified by a genetic analysis involving more than 223,000 participants in 43 genetic studies. A large multicenter team of investigators showed that genetic polymorphisms resulting in a less active 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene are associated with lower LDL cholesterol, slightly higher body weight and waist circumference, and increased plasma insulin and plasma glucose. The investigators showed that the more of these alleles an individual possessed, the greater the risk of type 2 diabetes (Lancet. 2015 Jan 24;385[9965]:351-61).
Hemorrhagic stroke: In the SPARCL study (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), 4,731 patients with a recent stroke or transient ischemic attack – 67% of which were ischemic strokes, 2% hemorrhagic strokes – were randomized to high-dose atorvastatin or placebo. Atorvastatin for secondary prevention markedly reduced the overall stroke risk. But this was due to a dramatic decrease in ischemic strokes. The incidence of hemorrhagic stroke was 2.3% in patients on atorvastatin at 80 mg/day for secondary prevention, compared with 1.4% in placebo-treated controls.
In multivariate analysis, the SPARCL investigators found that hemorrhagic stroke risk was increased by an adjusted 68% in patients on atorvastatin, 465% in patients whose prior stroke was hemorrhagic, and 519% in patients with a blood pressure reading of 160-179/100-109 mm Hg at their last clinic visit prior to the hemorrhagic stroke (Neurology. 2008 Jun 10;70[24 Pt 2]:2364-70).
Hepatic dysfunction: This event is extremely rare, so much so that it’s not listed as a side effect in statin labeling. Monitoring of liver function tests is no longer recommended in patients on statin therapy. If elevated tests are seen, find out about the patient’s alcohol consumption – the explanation is far more likely to lie there, according to Dr. Vogel.
What about the safety of the PCSK9 inhibitors?
Dr. Vogel is the U.S. national coordinator for the ongoing phase 3 ODYSSEY Outcomes Study, which is due to report initial results at the 2018 annual meeting of the American College of Cardiology. So far, albeit with only a couple of years worth of data in the large randomized outcome trials, the PCSK9 inhibitors haven’t been associated with muscle problems, cognitive impairment, hepatic dysfunction, or hemorrhagic stroke.
“I think we will eventually see an increased risk of hemorrhagic stroke. I don’t know why we wouldn’t because the mechanism is an antiplatelet mechanism, as with statins. But I don’t know what the incidence will be,” he said.
The EBBINGHAUS substudy of the ongoing FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) of the PCSK9 inhibitor evolocumab(Repatha) provides welcome data on cognition. EBBINGHAUS included 1,974 patients with atherosclerotic cardiovascular disease and normal cognition at baseline who underwent serial testing using the Cambridge Neuropsychological Test Automated Battery over the course of 2 years of prospective follow-up. No signal was seen of any impairment in spatial working memory, learning ability, or the elements of executive function, including planning, organization, and attention. Nor did structured assessment of patient self-reported everyday cognition differ between the active treatment and control arms. Ditto for investigators’ assessment of cognitive adverse events. Moreover, when it did occur, measurable cognitive decline proved unrelated to achieved LDL cholesterol level.
“Two-year data is not 20-year data. And cognitive decline is of great concern. Those of us in this field are going to remain vigilant and look for this, but at least for the present, when you put a patient on a PCSK9 inhibitor and see an LDL drop to 15 or 10 mg/dL – and you will see that happen – the data so far say we do not see cognitive decline,” Dr. Vogel said.
He reported serving as a paid consultant to the National Football League and receiving a research grant from and serving on the speakers bureau for Sanofi.
SNOWMASS, COLO. – One of the toughest tasks in all of preventive cardiology is to convince statin-phobic patients at increased cardiovascular risk that they should take a statin, Robert A. Vogel, MD, observed.
“The two hardest challenges I have in my practice are getting people to stop smoking and getting people who have fear of statins to take statins. That’s half my practice. ,” declared Dr. Vogel, a cardiologist at the University of Colorado, Denver.
“There is one true harm of a statin that I always worry about, and that’s hemorrhagic stroke. It’s rare, but it does occur,” the cardiologist said at the Annual Cardiovascular Conference at Snowmass.
Dr. Vogel highlighted key studies that he believes have convincingly addressed impaired cognition and other proposed statin side effects. He also provided an update on the safety profile of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.
Neurocognitive problems: The Food and Drug Administration really ratcheted up patient fretting when it mandated in 2012 that the labeling for all statins must include a warning of postmarketing reports of adverse events involving ill-defined memory impairment and confusion that were reversed upon drug discontinuation.
“I can tell you, I’ve had dozens of patients come in and say, ‘What about this warning? I’m afraid of dementia,’ ” Dr. Vogel said.
It’s tough to refute anecdotal case reports, but Dr. Vogel pointed to several published meta-analyses of prospective cohort studies, randomized controlled trials, and cross-sectional studies to illustrate his point. For example, investigators at Johns Hopkins University in Baltimore analyzed the results of 16 high-quality randomized trials and prospective cohort studies and found that the short-term studies showed no effect of statin therapy on measurable cognitive endpoints. Moreover, the pooled results of eight long-term studies, including more than 23,000 patients, showed a significant 29% reduction in new-onset dementia in statin-treated patients (Mayo Clin Proc. 2013 Nov;88[11]1213-21).
Another meta-analysis, this one including 27 studies, concluded there is “moderate-quality evidence” to suggest statin users have no increased incidence of dementia, mild cognitive impairment, or any change in neurocognitive scores related to executive function, declarative memory, processing speed, or global cognitive performance.
In this same report, the investigators delved into the FDA’s adverse event reporting database and determined that the rate of reported cognitive-related adverse events was 1.9 cases per 1 million statin prescriptions, identical to the rate for clopidogrel and essentially the same as the 1.6 cases per 1 million rate for losartan (Ann Intern Med. 2013 Nov 19;159[10]:688-97).
“It shows that if you take any drug and put it in the type of population we give these drugs to, you’re going to see about the same frequency of these anecdotal reports, with no signal that statins are any worse than any other drugs we use in cardiology. Is this proof that statins don’t cause cognitive impairment? No, but it’s suggestive that if you give drugs, people have adverse events that may or may not be related to those drugs. So this was reassuring to me that we’ll see this stuff anecdotally, but it probably isn’t due to the statin itself,” Dr. Vogel continued.
Myalgia: In the STOMP study (Effect of Statins on Skeletal Muscle Function and Performance), investigators at Hartford (Conn.) Hospital randomized 420 healthy, statin-naive subjects in a double-blind fashion to 80 mg/day of atorvastatin or placebo for 6 months. The incidence of myalgia was 9.4% in the atorvastatin group compared with 4.6% in placebo-treated controls. Of note, muscle strength on formal testing wasn’t reduced to a greater extent in myalgic patients on atorvastatin than in myalgic patients on placebo (Circulation. 2013 Jan 1;127[1]:96-103).
“There is a signal there,” Dr. Vogel commented. “So the true [placebo-subtracted] incidence of myalgias on a high-dose statin is about 5%. It’s not 20%, it’s not 30%, it’s about 1 patient in 20. It’s real, but it’s not everybody. Those are the numbers you have to think about. If half your patients on statin therapy are getting myalgias, you need to go into a different practice because you’ve got a bunch of Web-searching patients.”
Diabetes: A meta-analysis of 13 randomized controlled trials of statins with more than 91,000 participants and a mean of 4 years of follow-up concluded that for every 255 patients treated with a statin for 4 years, there would be one extra case of new-onset type 2 diabetes, a harm dwarfed by the reduction in cardiovascular events (Lancet. 2010 Feb 27;375[9716]:735-42).
The mechanism for this statin-related, slightly increased risk of developing type 2 diabetes has been clarified by a genetic analysis involving more than 223,000 participants in 43 genetic studies. A large multicenter team of investigators showed that genetic polymorphisms resulting in a less active 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene are associated with lower LDL cholesterol, slightly higher body weight and waist circumference, and increased plasma insulin and plasma glucose. The investigators showed that the more of these alleles an individual possessed, the greater the risk of type 2 diabetes (Lancet. 2015 Jan 24;385[9965]:351-61).
Hemorrhagic stroke: In the SPARCL study (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), 4,731 patients with a recent stroke or transient ischemic attack – 67% of which were ischemic strokes, 2% hemorrhagic strokes – were randomized to high-dose atorvastatin or placebo. Atorvastatin for secondary prevention markedly reduced the overall stroke risk. But this was due to a dramatic decrease in ischemic strokes. The incidence of hemorrhagic stroke was 2.3% in patients on atorvastatin at 80 mg/day for secondary prevention, compared with 1.4% in placebo-treated controls.
In multivariate analysis, the SPARCL investigators found that hemorrhagic stroke risk was increased by an adjusted 68% in patients on atorvastatin, 465% in patients whose prior stroke was hemorrhagic, and 519% in patients with a blood pressure reading of 160-179/100-109 mm Hg at their last clinic visit prior to the hemorrhagic stroke (Neurology. 2008 Jun 10;70[24 Pt 2]:2364-70).
Hepatic dysfunction: This event is extremely rare, so much so that it’s not listed as a side effect in statin labeling. Monitoring of liver function tests is no longer recommended in patients on statin therapy. If elevated tests are seen, find out about the patient’s alcohol consumption – the explanation is far more likely to lie there, according to Dr. Vogel.
What about the safety of the PCSK9 inhibitors?
Dr. Vogel is the U.S. national coordinator for the ongoing phase 3 ODYSSEY Outcomes Study, which is due to report initial results at the 2018 annual meeting of the American College of Cardiology. So far, albeit with only a couple of years worth of data in the large randomized outcome trials, the PCSK9 inhibitors haven’t been associated with muscle problems, cognitive impairment, hepatic dysfunction, or hemorrhagic stroke.
“I think we will eventually see an increased risk of hemorrhagic stroke. I don’t know why we wouldn’t because the mechanism is an antiplatelet mechanism, as with statins. But I don’t know what the incidence will be,” he said.
The EBBINGHAUS substudy of the ongoing FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) of the PCSK9 inhibitor evolocumab(Repatha) provides welcome data on cognition. EBBINGHAUS included 1,974 patients with atherosclerotic cardiovascular disease and normal cognition at baseline who underwent serial testing using the Cambridge Neuropsychological Test Automated Battery over the course of 2 years of prospective follow-up. No signal was seen of any impairment in spatial working memory, learning ability, or the elements of executive function, including planning, organization, and attention. Nor did structured assessment of patient self-reported everyday cognition differ between the active treatment and control arms. Ditto for investigators’ assessment of cognitive adverse events. Moreover, when it did occur, measurable cognitive decline proved unrelated to achieved LDL cholesterol level.
“Two-year data is not 20-year data. And cognitive decline is of great concern. Those of us in this field are going to remain vigilant and look for this, but at least for the present, when you put a patient on a PCSK9 inhibitor and see an LDL drop to 15 or 10 mg/dL – and you will see that happen – the data so far say we do not see cognitive decline,” Dr. Vogel said.
He reported serving as a paid consultant to the National Football League and receiving a research grant from and serving on the speakers bureau for Sanofi.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Isolated severe tricuspid regurgitation: An emerging disease
SNOWMASS, COLO. – that’s treatable, provided affected patients are referred for surgery before the clinical course progresses to intractable right heart disease with cirrhosis and liver failure, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.
“This is an emerging disease that you’re all going to see in your practices this year. You’ve got to know what to do with these patients. Get to them early,” urged Dr. Nishimura, professor of cardiovascular sciences and hypertension at the Mayo Clinic in Rochester, Minn.
The medical textbooks don’t discuss isolated severe tricuspid regurgitation (ISTR) or its etiology. ISTR is a disorder of progressive right ventricular dilation and dysfunction whose etiology involves either longstanding atrial fibrillation or valvular disruption due to interference from a crossing lead of a permanent pacemaker or implantable cardioverter defibrillator.
“This is something different. These patients have a normal left heart and left heart valves and normal pressures, with no pulmonary hypertension. So it doesn’t fit into any of the textbook categories of tricuspid regurgitation,” the cardiologist said. 
Moreover, the current American College of Cardiology/American Heart Association guidelines on valvular heart disease don’t address ISTR, either. Physicians who attempt to apply the guidelines in deciding when to refer a patient with ISTR for surgery will oftentimes find they’ve waited too long and the patient has started to develop end-stage disease, according to Dr. Nishimura.
And he should know: He was lead author of the current ACC/AHA guidelines (J Am Coll Cardiol. 2014 Jun 10;63[22]:2438-88).
Decades ago, Eugene Braunwald, MD, of Harvard Medical School, Boston, famously called the tricuspid valve “the forgotten valve.” The history of the Snowmass winter cardiology conference bears that out. During 2007-2017, the conference featured an average of 5.4 sessions per year on aortic valve disease, 4.5 sessions per year on mitral valve disease, and not a single session on tricuspid valve disease. But the tricuspid valve is forgotten no longer, Dr. Nishimura emphasized.
How ISTR presents
The affected patient has a history of either longstanding atrial fibrillation or a permanent pacemaker or ICD.
“This is something that 4 or 5 years ago people said didn’t exist. Our pacemaker people told me, ‘Nah, you can never get tricuspid regurgitation from our leads.’ Now it’s one of the leading causes of tricuspid regurgitation going to operation,” said Dr. Nishimura.
The presenting symptoms of ISTR are typically ascites, edema, and shortness of breath.
“Why should patients with a right heart problem get dyspnea? It turns out that when the right ventricle dilates it pushes the septum in, so the effective operative compliance of the left ventricle decreases and you actually see the pulmonary artery wedge pressure go up,” he explained.
On physical examination, the patient will have elevated jugular venous pressure with large V waves.
“This is a clue that something is going on. The patient will have neck veins jumping up to her ear lobes. The ear lobes are going to wiggle with every heart beat – boom, boom, boom. If you see that, you start to figure out what’s going on. You need nothing else,” Dr. Nishimura said.
The patient will likely also have a pulsatile enlarged liver and, even though this is valve disease, a murmur that’s either soft or inaudible.
Echocardiographic diagnosis
Echocardiography will show a dilated right ventricle and right atrium, a dilated inferior vena cava, and a normal left ventricle with no pulmonary hypertension. The classic sign of ISTR on continuous wave Doppler echocardiography is a dagger-shaped tricuspid regurgitation peak velocity signal of less than 2.5 meters/sec, which indicates the absence of pulmonary hypertension. This dagger shape occurs because the right atrial pressure equalizes the right ventricular pressure.
It’s also important to point the echo probe at the hepatic veins to spot another echocardiographic hallmark of ISTR: systolic reversal.
A thorough echo exam makes hemodynamic catheterization unnecessary in these patients, Dr. Nishimura added.
When to refer for tricuspid valve repair or replacement
The clinical course of ISTR is progressive, often rapidly so. It starts with elevated jugular venous pressure, then comes fatigue and shortness of breath, moving on to ascites and edema, then finally cirrhosis and renal failure. It’s a vicious cycle in which tricuspid regurgitation begets annular dilation, which causes chordal stretching and worsening tricuspid regurgitation, leading to further annular dilation.
Patients typically aren’t referred for surgery – and may not even present to a physician – until they’ve already developed end-stage disease. That’s probably why the outcomes of surgery for ISTR are so poor. Dr. Nishimura was senior investigator of a recent retrospective study of national trends and outcomes for ISTR surgery based on the National Inpatient Sample. The number of operations increased by 250% during a recent 10-year period, but the surgery is still rare: 290 operations in 2004, climbing to 780 nationwide in 2013.
In-hospital mortality remained steady over time at 8.8%, far higher than rates of in-hospital mortality for surgery for aortic and mitral valve disease, which today stand at 1%-2% or less. The adjusted risk of in-hospital mortality for tricuspid valve replacement in patients with ISTR was 1.9-fold greater than for valve repair (J Am Coll Cardiol. 2017 Dec 19;70[24]:2953-60).
“I think the reason the operative risk of valve surgery for ISTR is so high is that we’re waiting until patients have end-stage disease,” Dr. Nishimura said.
Indeed, he recommends referral for surgery as soon as the echocardiographic diagnosis of ISTR is made in a patient with huge neck veins.
“This will probably take the operative risk down by going to a time when the right ventricle can still recover,” he added.
In a patient with ISTR and pacemaker or defibrillator leads crossing the valve, tricuspid valve repair or replacement should be accompanied by exteriorization of the leads.
Dr. Nishimura reported having no financial conflicts of interest regarding his presentation.
SNOWMASS, COLO. – that’s treatable, provided affected patients are referred for surgery before the clinical course progresses to intractable right heart disease with cirrhosis and liver failure, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.
“This is an emerging disease that you’re all going to see in your practices this year. You’ve got to know what to do with these patients. Get to them early,” urged Dr. Nishimura, professor of cardiovascular sciences and hypertension at the Mayo Clinic in Rochester, Minn.
The medical textbooks don’t discuss isolated severe tricuspid regurgitation (ISTR) or its etiology. ISTR is a disorder of progressive right ventricular dilation and dysfunction whose etiology involves either longstanding atrial fibrillation or valvular disruption due to interference from a crossing lead of a permanent pacemaker or implantable cardioverter defibrillator.
“This is something different. These patients have a normal left heart and left heart valves and normal pressures, with no pulmonary hypertension. So it doesn’t fit into any of the textbook categories of tricuspid regurgitation,” the cardiologist said.
Moreover, the current American College of Cardiology/American Heart Association guidelines on valvular heart disease don’t address ISTR, either. Physicians who attempt to apply the guidelines in deciding when to refer a patient with ISTR for surgery will oftentimes find they’ve waited too long and the patient has started to develop end-stage disease, according to Dr. Nishimura.
And he should know: He was lead author of the current ACC/AHA guidelines (J Am Coll Cardiol. 2014 Jun 10;63[22]:2438-88).
Decades ago, Eugene Braunwald, MD, of Harvard Medical School, Boston, famously called the tricuspid valve “the forgotten valve.” The history of the Snowmass winter cardiology conference bears that out. During 2007-2017, the conference featured an average of 5.4 sessions per year on aortic valve disease, 4.5 sessions per year on mitral valve disease, and not a single session on tricuspid valve disease. But the tricuspid valve is forgotten no longer, Dr. Nishimura emphasized.
How ISTR presents
The affected patient has a history of either longstanding atrial fibrillation or a permanent pacemaker or ICD.
“This is something that 4 or 5 years ago people said didn’t exist. Our pacemaker people told me, ‘Nah, you can never get tricuspid regurgitation from our leads.’ Now it’s one of the leading causes of tricuspid regurgitation going to operation,” said Dr. Nishimura.
The presenting symptoms of ISTR are typically ascites, edema, and shortness of breath.
“Why should patients with a right heart problem get dyspnea? It turns out that when the right ventricle dilates it pushes the septum in, so the effective operative compliance of the left ventricle decreases and you actually see the pulmonary artery wedge pressure go up,” he explained.
On physical examination, the patient will have elevated jugular venous pressure with large V waves.
“This is a clue that something is going on. The patient will have neck veins jumping up to her ear lobes. The ear lobes are going to wiggle with every heart beat – boom, boom, boom. If you see that, you start to figure out what’s going on. You need nothing else,” Dr. Nishimura said.
The patient will likely also have a pulsatile enlarged liver and, even though this is valve disease, a murmur that’s either soft or inaudible.
Echocardiographic diagnosis
Echocardiography will show a dilated right ventricle and right atrium, a dilated inferior vena cava, and a normal left ventricle with no pulmonary hypertension. The classic sign of ISTR on continuous wave Doppler echocardiography is a dagger-shaped tricuspid regurgitation peak velocity signal of less than 2.5 meters/sec, which indicates the absence of pulmonary hypertension. This dagger shape occurs because the right atrial pressure equalizes the right ventricular pressure.
It’s also important to point the echo probe at the hepatic veins to spot another echocardiographic hallmark of ISTR: systolic reversal.
A thorough echo exam makes hemodynamic catheterization unnecessary in these patients, Dr. Nishimura added.
When to refer for tricuspid valve repair or replacement
The clinical course of ISTR is progressive, often rapidly so. It starts with elevated jugular venous pressure, then comes fatigue and shortness of breath, moving on to ascites and edema, then finally cirrhosis and renal failure. It’s a vicious cycle in which tricuspid regurgitation begets annular dilation, which causes chordal stretching and worsening tricuspid regurgitation, leading to further annular dilation.
Patients typically aren’t referred for surgery – and may not even present to a physician – until they’ve already developed end-stage disease. That’s probably why the outcomes of surgery for ISTR are so poor. Dr. Nishimura was senior investigator of a recent retrospective study of national trends and outcomes for ISTR surgery based on the National Inpatient Sample. The number of operations increased by 250% during a recent 10-year period, but the surgery is still rare: 290 operations in 2004, climbing to 780 nationwide in 2013.
In-hospital mortality remained steady over time at 8.8%, far higher than rates of in-hospital mortality for surgery for aortic and mitral valve disease, which today stand at 1%-2% or less. The adjusted risk of in-hospital mortality for tricuspid valve replacement in patients with ISTR was 1.9-fold greater than for valve repair (J Am Coll Cardiol. 2017 Dec 19;70[24]:2953-60).
“I think the reason the operative risk of valve surgery for ISTR is so high is that we’re waiting until patients have end-stage disease,” Dr. Nishimura said.
Indeed, he recommends referral for surgery as soon as the echocardiographic diagnosis of ISTR is made in a patient with huge neck veins.
“This will probably take the operative risk down by going to a time when the right ventricle can still recover,” he added.
In a patient with ISTR and pacemaker or defibrillator leads crossing the valve, tricuspid valve repair or replacement should be accompanied by exteriorization of the leads.
Dr. Nishimura reported having no financial conflicts of interest regarding his presentation.
SNOWMASS, COLO. – that’s treatable, provided affected patients are referred for surgery before the clinical course progresses to intractable right heart disease with cirrhosis and liver failure, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.
“This is an emerging disease that you’re all going to see in your practices this year. You’ve got to know what to do with these patients. Get to them early,” urged Dr. Nishimura, professor of cardiovascular sciences and hypertension at the Mayo Clinic in Rochester, Minn.
The medical textbooks don’t discuss isolated severe tricuspid regurgitation (ISTR) or its etiology. ISTR is a disorder of progressive right ventricular dilation and dysfunction whose etiology involves either longstanding atrial fibrillation or valvular disruption due to interference from a crossing lead of a permanent pacemaker or implantable cardioverter defibrillator.
“This is something different. These patients have a normal left heart and left heart valves and normal pressures, with no pulmonary hypertension. So it doesn’t fit into any of the textbook categories of tricuspid regurgitation,” the cardiologist said.
Moreover, the current American College of Cardiology/American Heart Association guidelines on valvular heart disease don’t address ISTR, either. Physicians who attempt to apply the guidelines in deciding when to refer a patient with ISTR for surgery will oftentimes find they’ve waited too long and the patient has started to develop end-stage disease, according to Dr. Nishimura.
And he should know: He was lead author of the current ACC/AHA guidelines (J Am Coll Cardiol. 2014 Jun 10;63[22]:2438-88).
Decades ago, Eugene Braunwald, MD, of Harvard Medical School, Boston, famously called the tricuspid valve “the forgotten valve.” The history of the Snowmass winter cardiology conference bears that out. During 2007-2017, the conference featured an average of 5.4 sessions per year on aortic valve disease, 4.5 sessions per year on mitral valve disease, and not a single session on tricuspid valve disease. But the tricuspid valve is forgotten no longer, Dr. Nishimura emphasized.
How ISTR presents
The affected patient has a history of either longstanding atrial fibrillation or a permanent pacemaker or ICD.
“This is something that 4 or 5 years ago people said didn’t exist. Our pacemaker people told me, ‘Nah, you can never get tricuspid regurgitation from our leads.’ Now it’s one of the leading causes of tricuspid regurgitation going to operation,” said Dr. Nishimura.
The presenting symptoms of ISTR are typically ascites, edema, and shortness of breath.
“Why should patients with a right heart problem get dyspnea? It turns out that when the right ventricle dilates it pushes the septum in, so the effective operative compliance of the left ventricle decreases and you actually see the pulmonary artery wedge pressure go up,” he explained.
On physical examination, the patient will have elevated jugular venous pressure with large V waves.
“This is a clue that something is going on. The patient will have neck veins jumping up to her ear lobes. The ear lobes are going to wiggle with every heart beat – boom, boom, boom. If you see that, you start to figure out what’s going on. You need nothing else,” Dr. Nishimura said.
The patient will likely also have a pulsatile enlarged liver and, even though this is valve disease, a murmur that’s either soft or inaudible.
Echocardiographic diagnosis
Echocardiography will show a dilated right ventricle and right atrium, a dilated inferior vena cava, and a normal left ventricle with no pulmonary hypertension. The classic sign of ISTR on continuous wave Doppler echocardiography is a dagger-shaped tricuspid regurgitation peak velocity signal of less than 2.5 meters/sec, which indicates the absence of pulmonary hypertension. This dagger shape occurs because the right atrial pressure equalizes the right ventricular pressure.
It’s also important to point the echo probe at the hepatic veins to spot another echocardiographic hallmark of ISTR: systolic reversal.
A thorough echo exam makes hemodynamic catheterization unnecessary in these patients, Dr. Nishimura added.
When to refer for tricuspid valve repair or replacement
The clinical course of ISTR is progressive, often rapidly so. It starts with elevated jugular venous pressure, then comes fatigue and shortness of breath, moving on to ascites and edema, then finally cirrhosis and renal failure. It’s a vicious cycle in which tricuspid regurgitation begets annular dilation, which causes chordal stretching and worsening tricuspid regurgitation, leading to further annular dilation.
Patients typically aren’t referred for surgery – and may not even present to a physician – until they’ve already developed end-stage disease. That’s probably why the outcomes of surgery for ISTR are so poor. Dr. Nishimura was senior investigator of a recent retrospective study of national trends and outcomes for ISTR surgery based on the National Inpatient Sample. The number of operations increased by 250% during a recent 10-year period, but the surgery is still rare: 290 operations in 2004, climbing to 780 nationwide in 2013.
In-hospital mortality remained steady over time at 8.8%, far higher than rates of in-hospital mortality for surgery for aortic and mitral valve disease, which today stand at 1%-2% or less. The adjusted risk of in-hospital mortality for tricuspid valve replacement in patients with ISTR was 1.9-fold greater than for valve repair (J Am Coll Cardiol. 2017 Dec 19;70[24]:2953-60).
“I think the reason the operative risk of valve surgery for ISTR is so high is that we’re waiting until patients have end-stage disease,” Dr. Nishimura said.
Indeed, he recommends referral for surgery as soon as the echocardiographic diagnosis of ISTR is made in a patient with huge neck veins.
“This will probably take the operative risk down by going to a time when the right ventricle can still recover,” he added.
In a patient with ISTR and pacemaker or defibrillator leads crossing the valve, tricuspid valve repair or replacement should be accompanied by exteriorization of the leads.
Dr. Nishimura reported having no financial conflicts of interest regarding his presentation.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS