Meet the Press at ACC.16
Whenever experts meet the press, the results can be interesting, entertaining, and infuriating—occasionally, all at the same time.
Here are highlights of those cardiovascular experts deserving hazard pay for putting themselves on the front line with reporters at ACC.16.
The Heart Outcomes Prevention Evaluation (HOPE)-3 trial was a double-blind, randomized, placebo-controlled trial of 12,705 men (≥ 55 years of age) and women (≥ 60 years of age) without cardiovascular disease but with intermediate risk. They were randomly assigned to cholesterol-lowering therapy with rosuvastatin (10 mg/day) or placebo and randomly assigned again to blood-pressure-lowering treatment with candesartan (16 mg/day) plus hydrochlorothiazide (12.5 mg/day) or placebo for a median of 5.6 years.
Neither blood-pressure-lowering drug has been shown to reduce the risk of cardiovascular events at such low doses, so it’s no surprise that Eva Lonn, MD, McMaster University, Hamilton, Ontario, told the press: “The fixed-dose combination of candasartan and hydrochlorothiazide reduced blood pressure by 6/3 mm Hg but did not reduce cardiovascular events, although we did observe cardiovascular event reduction in those with higher baseline systolic blood pressures.” (The trial confirmed that statins work: rosuvastatin resulted in a 24% lower risk of cardiovascular events compared to placebo and an absolute difference of 1.1 percentage points).
Dr. Lonn’s colleague at McMaster, Salim Yusuf, MD, DPhil, who helmed the cholesterol-lowering arm of the study, said, “HOPE-3 is the first formal testing of the polypill concept on clinical events—it’s not a polypill but it’s a concept—and the concept is valid in those with elevated blood pressure, but not in others.” He also said statins should be used more widely and you don’t need to measure lipids to use them.”
Kim Williams, Sr., MD, Rush University Medical Center, Chicago, IL, and now immediate past president of the ACC, noted, “HOPE-3 tells us: Don’t give blood pressure therapy to people with a blood pressure of 122 mm Hg and if it’s above 143 mm Hg, take it seriously because you can make a big difference in outcomes over a short period of time.”
Added Dr. Yusuf, “We have to simplify prevention; otherwise it simply won’t be widely used.”
– Online before print in a trio of papers in the New England Journal of Medicine
AS Blockade Hits the Ceiling
In one of the largest trials ever conducted in patients with heart failure and reduced ejection fraction, the ATMOSPHERE trial came down to earth. “We found that the addition of aliskiren to an evidence-based dose of enalapril—which was, by the way, almost 19 mg/day—simply led to more adverse effects without any increase in benefit,” according to lead-author John McMurray, MD, University of Glasgow, UK.
He added, “The totality of evidence suggests that there is a ceiling to how much you can block the renin-angiotensin system (RAS), beyond which there is no more benefit, there is only harm.”
– NEJM online ahead of print
If Shock Doesn’t Work for Cardiac Arrest, What Does?
Only about 10% of people who suffer cardiac arrest outside the hospital survive. “Out-of-hospital cardiac arrest is a huge problem,” explained Peter Kudenchuk, MD, University of Washington, Seattle, WA. “It strikes more than 350,000 persons unexpectedly each year in the U.S. and more than 80,000 of these episodes are caused by shockable arrhythmias. The bad news is, in the majority of these episodes, shock doesn’t work.”
He reported on a 3-year study that randomized 3,026 patients with out-of-hospital cardiac arrest and was conducted by the Resuscitation Outcomes Consortium, which includes clinical sites in the United States and Canada. What makes a difference? Dr. Kudenchuk said that among the approximately 1,900 patients in the study whose cardiac arrest was witnessed by a bystander, survival was improved significantly from about 23% to 28% by use of either amiodarone or lidocaine compared to saline placebo, “when given by paramedics to patients with out-of-hospital cardiac arrest who had failed electrical shock treatment.” Though seemingly small, he noted, the increase in survival reported in this trial means 1,800 additional lives could potentially be saved each year from cardiac arrest.
He added, “In patients who have a bystander-witnessed cardiac arrest, both amiodarone and lidocaine significantly improve survival to hospital discharge, but in the group that was not witnessed, we saw no effect whatsoever from either of the two drugs.” Bottom line: “You can’t save everyone from cardiac arrest, but you try to save everyone—and the message I take from this trial is if you try, you will save the people who were witnessed and you will not hurt (those) who were not.”
– NEJM online ahead of print
Experimental Drug Fails to Protect Against Contrast- induced Injury
Deepak Bhatt, MD, MPH, Harvard Medical School, Boston, MA, said, “It’s common to undergo cardiac catheterization in the U.S. and elsewhere and, for patients who have baseline kidney disease, there is a real risk of that kidney disease getting worse from the contrast agent.”
Preclinical evidence suggested that CMX-2043 had antioxidant and cell membrane stabilizing effects and that these protective effects would translate into less kidney cell damage and heart muscle damage during stenting. “Unfortunately, this particular approach using this particular drug did not reduce acute kidney injury and there remains an unmet clinical need to find agents that reduce contrast nephropathy and protect kidneys during angiographic procedures,” said Dr. Bhatt.
ACC Vice President C. Michael Valentine, MD, Stroobants Cardiovascular Center, Lynchburg, VA, added, “There have been so many trials over the last 15 years trying to find an agent that helps us in the cath lab to prevent kidney damage and we continue to find that saline and limitation of contrast are the only things that really help us.”
Rate vs. Rhythm Control: Postop, Either Works
“About 30 to 50% of people who have heart surgery will develop postoperative atrial fibrillation,” according to Marc Gillinov, MD, Cleveland Clinic, OH, “and while it’s a complication that tends to go away no matter what we do, it is associated with increased risk of stroke, death, bleeding, and it costs the US health care system over $1 billion a year.”
Postoperative atrial fibrillation (AF) occurred in 695 of the 2,109 patients (33.0%) who were enrolled preoperatively by the Cardiothoracic Surgical Trials Network. Dr. Gillinov and colleagues randomly assigned 523 of these patients with new-onset AF to one approach or the other. “There is no clear advantage of rate control over rhythm control in terms of hospital days or complications, and most of the time the atrial fibrillation is going to be gone by 60 days no matter what we do,” he said.
Dr. Gillinov added, “An initial strategy of rate control in a hemodynamically stable patient is probably reasonable because you avoid the toxicity of amiodarone and, if you need to switch to rhythm control, you can usually do it fairly easily while the patient is still in hospital.”
– NEJM online ahead of print
Tiring but True: CETP Inhibitor Fails Again
It is the third failure in a class of drugs known as cholesteryl ester transfer protein (CETP) inhibitors, which are designed to disrupt the natural process by which high-density lipoprotein cholesterol is converted into low-density lipoprotein (LDL) cholesterol. “The bottom line from this study is that evacetrapib had really good lipid effects but it had absolutely no effect on major adverse cardiovascular events, despite the fact that it doubled the levels of good cholesterol and significantly lowered LDL cholesterol at the same time,” said Stephen Nicholls, MBBS, PhD, of the University of Adelaide, Australia.
It may be time to hit the brakes on ACCELERATE. Dr. Nicholls, the study’s first author, said, “I think we are becoming increasingly skeptical of whether these CETP inhibitors, at least in high-risk patients, will be of any use.”
Commenting on the trial, Frederick Masoudi, MD, of the University of Colorado, Denver, CO, said, “It is disappointing that evacetrapib was not beneficial but it was an important trial to do because we can’t make assumptions based on surrogates; we need hard outcome trials and this is exactly one of those.”
Statin Intolerance is Real and Alternative Therapy Works
“Somebody sitting across from you who has multiple risk factors for coronary disease and has an LDL cholesterol or 210 or 220 is an accident waiting to happen,” according to Steven Nissen, MD, at the Cleveland Clinic, OH.
Among patients with demonstrated statin intolerance based on muscle-related adverse effects, the use of evolocumab resulted in significantly lower LDL cholesterol levels after 24 weeks than ezetimibe. “These were people (who) everybody would agree needed to be treated and yet they would not take a statin because of muscle symptoms,” said Dr. Nissen.
He added, “What we learned from this trial is that you can document statin intolerance with a rechallenge procedure. It is a real disorder, and that alternative agents such as the PCSK9 inhibitors can produce profound LDL reductions with almost no patient experiencing intolerable muscle symptoms with the alternative therapy.”
– JAMA online ahead of print
PARTNER 2: Next Gen TAVR Device Scores in Intermediate-risk Patients
Susheel Kodali, MD, New York-Presbyterian/Columbia University Medical Center in New York City, NY, told the media last year (ACC.15), “We now have intermediate-risk data where we’re getting to a 30-day 1% mortality risk and a 1% stroke risk with TAVR; how much better data do we need?” He added that for several years now, the concept has been to consider TAVR when surgery is not a good option, but given the data, “maybe the conversation shouldn’t be ‘TAVR when surgery’s not a good option’ but rather TAVR is the preferred option—at least in 80-year olds.” (Average age at baseline in this trial was 82.6 years.)
One year later and the argument still holds. The lower-profile, next-generation valve was evaluated in PARTNER trial patients. “Improvements with the SAPIEN 3 valve have made this an easier procedure to perform,” said Vinoid Thourani, MD, Emory University School of Medicine, Atlanta. “And this study shows that we can do it with an extremely low risk of complications and mortality.”
He added, “We believe these results indicate that intermediate-risk patients with severe aortic stenosis should now also head towards transcatheter aortic valve replacement.”
In a large data set of more than 40,000 cases of TAVR performed in the first 4 years after the technology was approved by the U.S. Food and Drug Administration, John Carroll, MD, of the University of Colorado Hospital, Denver, CO, said, “TAVR outcomes are improving but the one (question) that needed to be studied was volume. This analysis shows that the effect of TAVR volume on risk adjusted in-hospital mortality is statistically significant and clinically meaningful.”
|Read the full Exclusive ACC.16 Coverage issue of CardioSource WorldNews.|
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