AHA 2010 research highlights:

A slideshow presentation

AHA 2010 Research Highlights

The American Heart Association (AHA) 2010 Scientific Sessions took

place in Chicago, IL, November 13-17, 2010.

Key trials presented at the sessions include:

ADVANCE: New LVAD equivalent to HeartMate II, nonrandomized study

shows

RAFT: CRT shows survival benefit for class 2 and 3 HF patients with 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, as a bridge to heart transplant,

according to a new multicenter trial carried out in the US. The

new device showed noninferiority when compared with 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, a 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 lifeRAFT 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, Pfizer) produced large reductions in both the risk of death and the

risk of 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 IV vasodilator nesiritide (Natrecor, Scios/Johnson &

Johnson), 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.

AHA/ASA Distinguished scientists 2010

Every year, the AHA recognizes a select group of prominent

scientists whose contributions to research have advanced the

understanding of cardiovascular disease and stroke.

Those named as 2010 AHA/ASA Distinguished Scientists

include: Martin Chalfie, PhD, FAHA (Columbia University, New

York, NY), Harlan M Krumholz, MD, SM, FAHA (Yale

University School of Medicine, New Haven, CT), Michael H

Criqui, MD, MPH, FAHA (University of California, San Diego

School of Medicine, La Jolla, CA), and Helen H Hobbs, MD,

FAHA (Howard Hughes Medical Institute, Chevy Chase, MD).

Dr Hobbs gave the 2010 Distinguished Scientist Lecture entitled

"Genetics and Cardiovascular Disease: Are We Getting to the

Heart of the Matter?"

ROCKET AF

(Randomized, Double-Blind Study Comparing Once-Daily Oral

Rivaroxaban With Adjusted-Dose Oral Warfarin for the

Prevention of Stroke in Subjects With Non-Valvular Atrial

Fibrillation)

Results: The new oral factor Xa inhibitor rivaroxaban (Xarelto,

Bayer/Johnson & Johnson) 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 of 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 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 to warfarin, but superiority analyses at odds for more information.

CLOSURE I

Results: There were no differences in the primary end point of

stroke or TIA at two years, all-cause mortality at 30 days, and

neurological mortality between 31 days and two years for

patients randomized to patent foramen ovale (PFO) closure

using the STARFlex closure device (NMT Medical) as well as

six 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 strokes 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, 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, GlaxoSmithKline), even at

the fairly high dose of 4 g/day for six months, didn't cut the risk

of 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 hope of preventing

several cardiovascular end points. And there clearly has been equipoise in the area of atrial fibrillation, with as many

studies producing positive as those producing 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 See Omega-3 PUFA caps don't suppress paroxysmal AF in randomized trial for more information.

Poster sessions

A total of 2103 posters were presented at the AHA 2010 Scientific Sessions.

The eight poster winners were:

Nuclear Cardiology and Outcomes, Incremental Value of Noninvasive Cardiac

Imaging in Risk Prediction: Results from the SPARC Study, presented by Marcelo

DiCarli

Body Composition and Mortality in Patients With Coronary Heart Disease - The

"Obesity Paradox," presented by Carl Lavie

Hypoxia Inducible Factor-1a Dependent miR-210 is a Critical Regulator of Paracrine

Activity in Preconditioned Mesenchymal Stem Cells for Angiogenic Growth Factor

Expression, presented by Shazia Durrani

Efficacy and Potency of Class 1 Antiarrhythmic Drugs for Suppression of Ca2+ Waves in Permeabilized Calsequestrin Null Myocytes,

presented by Eleonora Savio Galimberti

The Relationship of Rotors to Scar Border Zones and Dominant Frequency Domains in Human Ventricular Fibrillation, presented by

Stephane Masse

Vegetation Size Does Not Affect Stroke Risk in Infective Endocarditis After 5 Days of Effective Antimicrobial Therapy: An Analysis From the

International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), presented by Stuart Dickerman

The Endovascular Stent Graft Raises Vascular Stiffness and Changes Cardiac Structure within a Very Short Term, presented by Yasuharu

Takeda

Health Economics in the Platelet inhibition and Patient Outcomes (PLATO) Randomized Trial: Report on Within Trial Resource Use

Patterns, presented by Magnus Janzon

BASKET-PROVE

Results: Patients needing a coronary stent 3.0 mm in diameter

or larger were randomized to either a first-generation sirolimus-

eluting stent (Cypher Select, Cordis), a bare-metal cobalt-

chromium stent (Vision, Abbott), or a second-generation

everolimus-eluting stent (Xience V, Abbott Vascular). All patients

were prescribed aspirin and clopidogrel for at least one year

postimplant. The rates of the primary end point, a composite of

death from cardiac causes or nonfatal MI at two years, were

statistically similar for all three 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 the DES patients and bare-metal-

stent patients.

"[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 (Merck, Whitehouse Station, NJ)

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 later pulled from clinical testing after a

large morbidity and mortality trial revealed an increased risk of

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 five or more

antihypertensive medications is a big unmet clinical need, with

those affected being at increased risk of 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) in an

interview with heartwire.

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 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

randomized to receive atorvastatin (Lipitor, Pfizer), a significant

reduction in LDL-C corresponded to a significant drop in CV-

event risk at six months. But 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 of 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," Dr

Otavio Berwanger (Hospital do Coração, São Paulo, Brazil)

told heartwire. "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, that 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.

Opinions from AHA

Heartfelt with Dr Melissa Walton Shirley:

The HDL ceiling: Cracked today by DEFINE and the CETP inhibitor

anacetrapib

Ready, set, go! Let's see how long it takes us to stop using N-

acetylcysteinepost-ACT

DES safety in BASKET-PROVE; ACT on contrast-induced nephropathy;

dosing for clopidogrel nonresponders in GRAVITAS; TAMARIS on gene

therapy

Latest on atrial fibrillation with analysis of ROCKET AF ( and POM 3 (fish

oil supplements); SMART-AV on cardiac resynchronization; PFO closure

in CLOSURE I

Take the thrombin-inhibitor exam: Automatically win a million dollars if you

get 100% correct!

Three decades worth of proof: Minnesota cities prove critics of smoking-

cessation efforts wrong, wrong, WRONG!

Results, analysis, and clinical implications of leading heart-failure trials at

AHA 2010: Eplerenone in EMPHASIS-HF; CRT and RAFT; LVAD in

ADVANCE; nesiritide in ASCEND-HF

Gross pics of tobacco carnage: Reverse marketing or empty drama?

Private practice with Dr Seth Bilazarian:

GRAVITAS has immediate impact on my practice

New horizons for atrial fibrillation as ROCKET AF (rivaroxaban) follows on the heels of RE-LY (dabigatran)

Eplerenone, nesiritide, CRT, LVAD: Clinical implications of heart-failure trial results from AHA 2010

Physician wages across specialties: Cardiologists earn $93 per hour (for now)

Heart failure and transplantation with Dr Ileana Piña:

Petitioning the Social Security Administration for compassionate disability for HF, transplant, and congenital heart-disease patients

AHA 2010

Over 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.

For more information

AHA site

AHA 2010 Coverage on theheart.org

Medscape coverage AHA 2010

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.

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