Top new scientific studies from AHA Scientific sessions 2010
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PrintThe American Heart Association (AHA) 2010 Scientific Sessions took place in Chicago, Illinois, November 13-17, 2010. The following information is a summary of trials that were presented as reported by HeartWire.
Key trials presented at the sessions include:
- ADVANCE: New LVAD equivalent to HeartMate II, nonrandomized study shows
- RAFT: CRT shows survival benefit for patients with class 2 and 3 HF who have low EF and wide QRS
- EMPHASIS-HF: Eplerenone shows large benefits in milder heart failure
- ASCEND HF: Nesiritide safe but of limited dyspnea benefit in acute HF
- ROCKET AF: Rivaroxaban noninferior to warfarin, but superiority analyses at odds
- CLOSURE I: No overall benefit, no reduction in stroke or TIA with PFO closure
- GRAVITAS: No benefit of doubling dose in clopidogrel nonresponders
- P-OM3: Omega-3 PUFA caps don't suppress paroxysmal AF in randomized trial
- BASKET-PROVE: DES as safe as bare-metal stents in larger coronary arteries, with less TVR
- DEFINE: Large effects on LDL and HDL cholesterol with CETP inhibitor anacetrapib
- SYMPLICITY HTN: Catheter-based renal denervation reduces BP in patients with resistant hypertension
- ASCOT CRP: Analysis fuels debate over JUPITER-based CRP indication for statins
- ACT: No benefit of N-acetylcysteine to reduce contrast-induced nephropathy
ADVANCE: Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure
Results: A novel left ventricular assist device (LVAD) developed by a small company called HeartWare (Framingham, MA) is a viable alternative to the only other widely used LVAD, Thoratec's HeartMate II® (Pleasanton, CA), as a bridge to heart transplant, according to a new multicenter trial carried out in the United States. Data from the new device showed noninferiority when compared with data from patients in the INTERMACS national registry, most of whom had received the HeartMate II device.
"The early results show this is at least as good as the other available devices, and we hope this will translate into clinical benefit, but this is only the beginning. Adverse reactions have been a major problem that has dogged the application of LVADs," said Sir Magdi Yacoub (Harefield Hospital, Middlesex, UK), discussant of the trial at the AHA.
See: ADVANCE: New LVAD Equivalent to HeartMate II, Nonrandomized Study Shows for more information.
RAFT: Resynchronization/Defibrillation for Ambulatory Heart Failure Trial
Results: Cardiac resynchronization therapy (CRT) provided a survival benefit beyond that of implantable cardioverter defibrillator (ICD) therapy alone in patients with moderate heart failure symptoms, wide QRS complex, and left ventricular systolic dysfunction.
"This is a pretty important finding across a wide spectrum of patients. It will likely lead to revisions in the guidelines and changes in physician practice patterns, with more eligible patients being treated and benefiting from this important therapy," said Dr. Gregg Fonarow (University of California, Los Angeles).
See: CRT Is a Life RAFT for Class 2 and 3 HF Patients With Low EF and Wide QRS for more information.
EMPHASIS-HF: A Comparison of Outcomes in Patients in New York Heart Association (NYHA) Class II Heart Failure When Treated With Eplerenone or Placebo in Addition to Standard Heart Failure Medicines
Results: The aldosterone antagonist eplerenone (Inspra™) produced large reductions in both the risk for death and the risk for hospitalization compared with placebo in patients with systolic heart failure and mild symptoms.
"Before we recommend expanding the population to receive aldosterone antagonists, we need to learn how to use them without causing life-threatening hyperkalemia. This may be particularly true for patients with reduced renal function, diabetes, and advanced age," said the discussant of the study, Dr. Lynne Warner Stevenson (Brigham and Women's Hospital, Boston, MA).
See: EMPHASIS-HF: Eplerenone Shows Large Benefits in Milder Heart Failure for more information.
ASCEND HF: A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure
Results: The intravenous vasodilator nesiritide (Natrecor®), a mass-production version of a native natriuretic peptide, appears to be safe for use in acute decompensated heart failure but does not seem to have much more of an effect against acute dyspnea than conventional diuretics and vasodilators, both of which are less expensive.
"We constantly put drugs on the market without doing the right outcome trials. If this outcome trial had been done earlier, clinicians and patients would have had a much better idea of the potentially very limited role of this treatment, but they also would have known that it was not harmful," said chair of the ASCEND-HF executive committee, Dr. Robert Califf (Duke Clinical Research Institute, Durham, NC), speaking at a press conference at the AHA.
See: ASCEND-HF: Nesiritide Safe but of Limited Dyspnea Benefit in Acute HF for more information.
ROCKET AF: Randomized, Double-Blind Study Comparing Once-Daily Oral Rivaroxaban With Adjusted-Dose Oral Warfarin for the Prevention of Stroke in Subjects With Nonvalvular Atrial Fibrillation
Results: The new oral factor Xa inhibitor rivaroxaban (Xarelto®) was noninferior to dose-adjusted warfarin with regard to all-cause stroke and non-central nervous system (CNS) embolism, but the question of superiority over warfarin is less clear. In the intention-to-treat superiority analysis, investigators failed to show the drug had an advantage statistically over warfarin for the prevention of thromboembolic events in patients with nonvalvular atrial fibrillation. In an on-treatment analysis addressing the superiority question, however, rivaroxaban significantly reduced the risk for stroke or non-CNS embolization by 21% compared with warfarin.
"If you take away only the conclusion of noninferiority, that's a step up," said Dr. Douglas Zipes (Krannert Institute of Cardiology, Indianapolis, IN) speaking with heartwire. "Warfarin is a very difficult drug to use. Patients don't like the repeated INR [International Normalized Ratio] checks, and it's very difficult to maintain control. I have several patients with INRs all over the map, so to have another substitute for that is welcome. However, the on-treatment analysis shows superiority over warfarin, and while that's not the gold standard -- call it the silver standard -- I'm very impressed with the results."
See: Off Orbit? ROCKET AF: Rivaroxaban Noninferior but Not Superior, to Warfarin in ITT Analysis for more information.
CLOSURE I
Results: There were no differences in the primary endpoint of stroke or TIA at 2 years, all-cause mortality at 30 days, and neurologic mortality between 31 days and 2 years for patients randomly assigned to patent foramen ovale (PFO) closure using the STARFlex® closure device (NMT Medical, Boston, MA) and 6 months of aspirin and clopidogrel (and an additional 18 months of aspirin) compared with patients who received best medical therapy -- aspirin or warfarin or a combination.
"It is now clear that the selection of patients for PFO closure should be refined, and we cannot now consider closing PFO in all patients who have stroke of unknown cause. The term cryptogenic stroke is probably unnecessarily cryptic to many physicians and patients...too vague," said trial discussant Dr. Pierre Amarenco (Bichat Hospital, Paris, France).
See: CLOSURE I: No Overall Benefit, no Reduction in Stroke or TIA With PFO Closure for more information.
GRAVITAS: Gauging Responsiveness With a VerifyNow Assay-Impact on Thrombosis and Safety
Results: Patients receiving drug-eluting stents who showed high residual platelet activity, according to platelet-function tests with the VerifyNow® assay (Accumetrics, San Diego, CA), fared no better on a double dose of clopidogrel than patients who received the regular clopidogrel dose.
"In post-PCI patients with low-risk clinical presentations, a treatment strategy of high-dose clopidogrel for high residual reactivity on platelet-function testing is not warranted," concluded lead investigator Dr. Matthew Price (Scripps Clinic, La Jolla, CA), presenting the results to the media at the AHA 2010 Scientific Sessions.
See: GRAVITAS: No Benefit of Doubling Dose in Clopidogrel Nonresponders for more information.
P-OM3: Efficacy and Safety of Prescription Omega-3-Acid Ethyl Esters for the Prevention of Recurrent Symptomatic Atrial Fibrillation
Results: Taking prescription-only omega-3 polyunsaturated fatty-acid (PUFA) capsules (Lovaza®), even at the fairly high dose of 4 g/day for 6 months, didn't cut the risk for recurrence of symptomatic paroxysmal atrial fibrillation (AF). There was, however, "a reduction in average ventricular rate during the first AF recurrence, a reduction in triglyceride levels at week 24 that did not occur with placebo, and increased blood levels of the omega-3 fish oils eicosapentaenoic acid and docosahexaenoic acid compared with placebo patients," according to the study's authors.
"Many of our patients in fact do use fish oil products, in various doses and in various preparations, in the hope of preventing several cardiovascular endpoints. And there clearly has been equipoise in the area of atrial fibrillation, with as many studies producing positive as produce negative results," said lead investigator Dr. Peter R. Kowey (Lankenau Institute for Medical Research, Wynnewood, PA). The current study, he said, "is actually the first large randomized trial of this medication in a nonsurgical population."
See: Omega-3 PUFA Caps Don't Suppress Paroxysmal AF in Randomized Trial for more information.
BASKET-PROVE
Results: Patients needing a coronary stent 3.0 mm in diameter or larger were randomly assigned to either a first-generation sirolimus-eluting stent (Cypher® Select, Cordis Corporation, Bridgewater, NJ), a bare-metal cobalt-chromium stent (Vision, Abbott Laboratories, Abbott Park, IL), or a second-generation everolimus-eluting stent (Xience™ V, Abbott Vascular, Abbott Park, IL). All patients were prescribed aspirin and clopidogrel for at least 1 year postimplant. The rates of the primary endpoint, a composite of death from cardiac causes or nonfatal MI at 2 years, were statistically similar for all 3 groups. There were no significant differences in the rates of late events or the rates of death, MI, or stent thrombosis, but there was a significant difference in non-MI TVR rates between patients with DES and those with bare-metal-stents.
"[I]n contemporaneous stenting of large coronary arteries, late safety problems with drug-eluting stents could not be confirmed, and there was even a trend in the opposite direction," explained study investigator Dr. Christoph Kaiser (University Hospital, Basel, Switzerland).
See: BASKET-PROVE: DES as Safe as Bare-Metal Stents in Larger Coronary Arteries, With Less TVR for more information.
DEFINE: Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib
Results: The new cholesteryl ester transfer protein (CETP) inhibitor anacetrapib significantly decreased LDL-cholesterol levels by 36% and increased HDL-cholesterol levels by 138% when compared with placebo. Importantly, there was no increase in systolic blood pressure, an off-target effect that troubled torcetrapib, an earlier CETP inhibitor that was pulled from clinical testing after a large morbidity and mortality trial revealed an increased risk for mortality and cardiovascular events.
"It's game changer, but because we don't have hard clinical events, we can't say that it's a home run," Dr. Roger Blumenthal (Johns Hopkins Medical Institute, Baltimore, MD) told heartwire. "Still, in this short time [76 weeks], we see a decrease in total events and total revascularizations, and we weren't expecting that at all. We just wanted to see the safety of the drug. So, it's really exciting."
See: DEFINE: Large Effects on LDL and HDL Cholesterol With CETP Inhibitor Anacetrapib for more information.
SYMPLICITY HTN-2: Renal Denervation in Patients With Uncontrolled Hypertension
Results: A new technique, catheter-based renal denervation, used in patients with resistant hypertension resulted in significant reductions in blood pressure without any major complications. Severe, resistant hypertension that is uncontrolled despite patients taking 5 or more antihypertensive medications is a big unmet clinical need, with those affected being at increased risk for stroke and renal failure.
"There is nowhere to go for these patients. We think with this novel approach we can bring many of them under control. I've never seen BP falls as big as this from any other treatment process, which makes the possibility of cure realistic; it might be within reach. It has always been a dream of mine to come up with a cure for hypertension," said Dr. Murray D. Esler (Baker IDI Heart and Diabetes Institute, Melbourne, Australia).
See: A Revolutionary Road for Resistant Hypertension? Renal Denervation in Symplicity HTN-2 for more information.
ASCOT-CRP
Results: The addition of high-sensitivity C-reactive protein (hs-CRP) measurements didn't much improve conventional risk assessments in patients with hypertension and other CV risk factors but with normal or only modestly elevated LDL-cholesterol levels in a post hoc analysis of the ASCOT lipid-lowering arm. Moreover, among patients in the analysis who had been randomly assigned to receive atorvastatin (Lipitor®), a significant reduction in LDL-C corresponded to a significant drop in CV-event risk at 6 months. However, a significant fall in hs-CRP levels did not predict a decrease in CV events.
"These results do not support current proposals to measure CRP in the clinical setting, either to assign statins to individuals on the basis of an elevated CRP alone or to monitor CRP levels as an indicator of the efficacy of statin treatment," said ASCOT co-chair Dr. Peter S. Sever (Imperial College, London, UK).
See: ASCOT Analysis Fuels Debate Over JUPITER-Based CRP Indication for Statins for more information.
ACT: Acetylcysteine for Contrast-Induced Nephropathy Trial
Results: The addition of N-acetylcysteine failed to reduce the risk for contrast-induced nephropathy in patients undergoing coronary and vascular angiography.
"I would be comfortable saying that this is a definitive trial, and I'd be comfortable saying that because if you look at the other high-quality trials, we reached exactly the same result," said Dr. Otavio Berwanger (Hospital do Coração, São Paulo, Brazil). "It would be extremely unlikely that another trial would be conducted, say a larger 20,000-patient trial, and would find a different result. One thing that is interesting with negative trials is that there is often a subgroup, maybe sicker patients, the elderly, who might have a different result. But here, it was very consistent."
See: ACT: No Benefit of N-acetylcysteine to Reduce Contrast-Induced Nephropathy for more information.
AHA 2010
More than 23,500 people attended the AHA 2010 Scientific Sessions, which included: 1592 oral presentations, 2103 posters, and 16 late-breaking clinical trials.
Sessions were grouped into 7 core themes:
• Cardiovascular Imaging
• Epidemiology and Prevention of Cardiovascular Disease: Physiology, Pharmacology, and Lifestyle
• Genetics, Genomics, and Congenital Cardiovascular Disorders
• Heart Rhythm Disorders and Resuscitation Science
• Myocardium: Function and Failure
• Catheter-Based and Surgical Interventions
• Vascular Disease: Biology and Clinical Science
The 2011 AHA Scientific Sessions will be held November 12-16, 2011, at the Orange County Convention Center in Orlando, Florida.
This top news from AHA 2010 was adapted from Medscape Nurses from WebMD. Original article form Heartwire with credits as below:
Credits and Disclosures
Editor
Shelley Wood
Managing Editor, heartwire
theheart.org
Kelowna, BC
Disclosure: Shelley Wood has disclosed no relevant financial relationships.
Contributor
Steven Rourke
Manager, Editorial Programming
theheart.org
Montreal, QC
Disclosure: Steven Rourke has disclosed no relevant financial relationships.
Journalists
Lisa Nainggolan, theheart.org
London, UK
Disclosure: Lisa Nainggolan has disclosed no relevant financial relationships
Sue Hughes, theheart.org
London, UK
Disclosure: Sue Hughes has disclosed no relevant financial relationships.
Reed Miller, theheart.org
Bethesda, MD
Disclosure: Reed Miller has disclosed no relevant financial relationships.
Michael O'Riordan, theheart.org
Toronto, ON
Disclosure: Michael O'Riordan has disclosed no relevant financial relationships.
Steve Stiles, theheart.org
Fremont, CA
Disclosure: Steve Stiles has disclosed no relevant financial relationships.
