ESC 2010 research highlights:

A slideshow presentation

ESC 2010 Research Highlights

Key trials presented at the meeting include:

AVERROES: Apixaban yields significant reductions in stroke, no

increased bleeding.

SHIFT: Adding HR-slowing agent ivabradine to HF meds cuts mortality,

hospitalization.

ALPHA OMEGA Trial: n-3 fatty acids fail to reduce cardiovascular events

in post-MI patients.

EINSTEIN DVT: Rivaroxaban almost superior to usual care in treatment of

DVT.

FUTURA OASIS-8: Standard-dose heparin recommended during PCI to

avoid catheter thrombosis with fondaparinux.

LESSON 1: Everolimus bests sirolimus in nonrandomized DES face-off.

PLATO genetic substudies: No need for gene testing in PCI patients.

CURE/ACTIVE A: No effect of loss-of-function clopidogrel gene on event

rates in ACS or AF.

INNOVATE PCI: Elinogrel, a new antiplatelet agent, passes initial hurdles.

ATOLL: Study seen as supporting enoxaparin over standard heparin in

primary PCI.

COPPS: Colchicine halves incidence of postpericardiotomy syndrome.

RESPONSE: Nurse program "reasonably successful" for ACS secondary

prevention.

STAR-HEART: Stem cells associated with improved long-term

hemodynamics and reduced mortality in chronic heart failure

AVERROES (Apixaban versus Acetylsalicylic Acid to Prevent Strokes)

Results: Patients with atrial fibrillation unable to take warfarin

who were treated with the investigational oral factor Xa inhibitor

apixaban (Pfizer/Bristol-Myers Squibb) had a significantly lower

risk of stroke and systemic embolic events compared with

patients treated with aspirin. Importantly, there were no

observed increases in the risk of major bleeding, minor

bleeding, or intracranial hemorrhage, among other end points,

in those treated with apixaban.

"As a proof of principle, it's exciting, because these new drugs

are so selective just on one factor, like factor Xa, whereas

warfarin is much less selective, inhibiting around five factors, so

it makes sense that bleeding tends to be lower in these new

drugs," said Dr Harald Arnesen (Oslo University Hospital,

Norway), the scheduled discussant during the late-breaking

clinical-trials session. "The fact that the [bleeding] risks are

quite similar to aspirin is really quite exciting."

See AVERROES: Apixaban yields significant reductions in

stroke, no increased bleeding for more information.

SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial)

Results: Patients with chronic systolic heart failure who added ivabradine (Procoralan, Servier) to the medications they were

already taking showed a significant 18% drop in the composite rate of cardiovascular death or heart-failure hospitalization,

compared with a placebo control group, over a period of about two years.

"This is a very interesting study that tests a novel concept of heart-rate slowing as adjunctive therapy for heart failure," said Dr

Clyde Yancy (Baylor University Medical Center, Dallas, TX), who was not involved with the trial. "But," he added, "sufficient

questions remain regarding who would benefit most from this approach."

See SHIFT: Adding HR-slowing agent ivabradine to HF meds cuts mortality, hospitalization for more information.

ALPHA OMEGA

Results: Low-dose supplementation with the n-3 fatty acids

eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or

plant-derived alpha-linolenic acid (ALA) failed to reduce

cardiovascular events in a large cohort of patients who had

previously had an MI.

The investigators, including trial leader Dr Daan Kromhout

(Wageningen University, the Netherlands), say the negative

findings are likely the result of the optimal medical therapy that

patients in the trial were receiving following their index MI. All

patients were treated with "state-of-the-art antihypertensive,

antithrombotic, and lipid-modifying therapy," and this might

explain the discrepancy with previous studies that suggested n-3

fatty acids, particularly EPA, might be cardioprotective following

MI.

See Alpha Omega Trial: n-3 fatty acids fail to reduce

cardiovascular events in post-MI patients for more information.

EINSTEIN DVT

Results: The oral factor Xa inhibitor rivaroxaban (Xarelto,

Bayer/Johnson & Johnson) was found to be noninferior to

standard medical therapy for the treatment of acute symptomatic

deep vein thrombosis (DVT).

Dr Harry R Buller (Academic Medical Center, Amsterdam, the

Netherlands) said that rivaroxaban, an oral factor Xa inhibitor,

was close to demonstrating superiority, although the trial was

designed specifically to demonstrate noninferiority, because "the

standard medical treatment is so good." But although usual care

is effective, it is inconvenient, requiring initial subcutaneous

injections of low-molecular-weight heparin followed by

warfarin treatment, with its own attendant problems.

See Rivaroxaban almost superior to usual care in treatment of

DVT for more information.

Cardiologists of Tomorrow at ESC 2010

At this year's Congress, the ESC debuted a special educational

program for cardiologists-in-training, junior cardiologists under

the age of 35, and first-time attendees of the ESC interested in

refreshing their knowledge.

The program was a partnership between the ESC, the 52 ESC

national societies, and 28 ESC affiliate national societies. The

"Cardiologists of Tomorrow" program consisted of 42 sessions

on topics from treatment of hypertension to the genetic aspects

of arrhythmias. The sessions included clinical seminars, special

sessions, and regular symposia.

Prof Fausto Pinto, chair of the ESC Congress Program

Committee, awarded prizes to the following young investigators:

Joanna Hammond from Brussels, Belgium (basic science),

Andrew Ludman from London, UK (clinical science), Alexios

Antonopoulos from Athens, Greece (coronary pathophysiology

and microcirculation), Radoslaw Debiec from Leicester, UK

(population sciences), Sasha Koul from Lund, Sweden

(thrombosis), and Daurice Grossniklaus from Atlanta, GA, who

won the Atie Immink ward in nursing. The state-of-the-art

research awards in heart failure and CAD were awarded to

Katrin Walenta from Homburg/Saar, Germany and Pascal Lim

from Creteuil, France.

FUTURA/OASIS-8 (Fondaparinux Trial With UFH During Revascularization in Acute Coronary Syndromes)

Results: ACS patients undergoing PCI being treated with fondaparinux as the main anticoagulant should receive standard-dose

unfractionated heparin during the procedure to avoid catheter thromboses. Results of the trial showed no major advantages of low-

dose heparin over standard-dose heparin in such patients, and neither dose increased major bleeding when compared with the historical

control group of fondaparinux alone in the OASIS-5 trial.

"The trial has resolved this important issue with fondaparinux. It has shown that we can reduce the problem of catheter thrombosis

without increasing major bleeding. This means that ACS patients on fondaparinux can undergo PCI safely with adjunctive [intravenous]

IV heparin," said Dr Sanjit Jolly (McMaster University, Hamilton, ON), co-lead investigator of the trial, speaking at an ESC press

conference.

See: FUTURA/OASIS-8: Standard-dose heparin recommended during PCI to avoid catheter thrombosis with fondaparinux for more

information.

LESSON I

Results: Patients treated with everolimus-eluting stents showed

a 17% relative risk reduction in the primary end point of death,

MI, and TVR, compared with a patient cohort treated with

sirolimus-eluting stents, only narrowly missing statistical

significance (p=0.056). This nonrandomized comparison

provides some of the strongest evidence yet that so-called

"next-generation" drug-eluting stents (DES) may have an edge

in terms of safety and efficacy over the first drug-eluting stent

on the market.

Dr Stephan Windecker (Bern University Hospital, Switzerland),

who presented the results during a hot-line session at the ESC,

noted that the study just missed its primary end point but

showed statistically significant differences in rates of MI and

stent thrombosis. Windecker added that the trial was not

powered to look at the isolated clinical end points found to be

statistically significant in this study, calling the findings

"exploratory only."

See LESSON I: Everolimus bests sirolimus in nonrandomized

DES face-off. for more information.

PLATO genetic substudies

Results: Two genetic substudies of the large pivotal trials of the

new antiplatelet agents ticagrelor (Brilinta, AstraZeneca) and

prasugrel (Effient, Lilly) confirm that neither agent seems to be

affected by CYP2C19 loss-of-function alleles, which often indicate

poor outcomes in patients taking clopidogrel. Nor was either drug

affected by another genetic variation, in the ABCB1 gene, which

affects absorption of clopidogrel.

CURE/ACTIVE A Results: Loss-of-function CYP2C19 alleles did

not have any effect with regard to safety or efficacy of clopidogrel

(Plavix, Bristol-Myers Squibb/Sanofi-Aventis) in ACS and AF

patients participating in the CURE and ACTIVE A trials,

respectively, new results show. However, a gain-of-function

CYP2C19 allele was associated with a greater benefit of

clopidogrel in the CURE trial, but not the ACTIVE A trial.

See New PLATO data: No need for gene testing in PCI patients

and CURE ACTIVE: No effect of loss-of-function clopidogrel gene

on event rates in ACS or AF for more information.

INNOVATE PCI

Results: Treatment with oral and intravenous (IV) elinogrel

(Novartis), a novel antiplatelet agent, had more rapid antiplatelet

effects than clopidogrel (Plavix, Bristol Myers-Squibb/Sanofi-

Aventis) in acute and chronic phases of therapy for patients

undergoing nonurgent PCI in this phase 2 trial.

"I think, at this point, we're talking about potential advantages,

remembering this is a phase 2 trial, with this drug," said lead

investigator Dr Sunil Rao (Duke University Medical Center, Durham,

NC). "Remember that, based on recent clinical-trial data, there is a

suggestion that greater platelet inhibition is associated with better

ischemic outcomes, but that comes with a cost of increased bleeding

risk. The platelet trials suggest reversible platelet inhibition may

mitigate some of those risks and further improve outcomes. So, in

that sense, elinogrel has properties of reversible inhibition of the

CYP12 receptor, so it might reduce bleeding risk in patients."

See INNOVATE PCI: Elinogrel, a new antiplatelet agent, passes

initial hurdles for more information.

ESC 2010 Poster Sessions

3360 Abstracts were selected for poster presentations and 112 for

moderated poster presentations spread over four days at the ESC 2010

Congress.

Topics included: cardiomyopathies, lipids, atrial fibrillation, antithrombotic

agents, genetics and gene therapy, and the effects of culture and society

on heart disease.

ATOLL (STEMI Treated With Primary Angioplasty and Intravenous Lovenox or Unfractionated Heparin)

Results: About 900 patients undergoing PCI for acute STEMI were randomized to receive either IV enoxaparin or

unfractionated heparin (UFH) with the procedure. The two groups' subsequent 30-day rates of a complex composite primary

end point that included death and major bleeding were not significantly different, although the enoxaparin group showed a

favorable trend. Also, the low-molecular-weight heparin (LMWH) roundly outperformed UFH for most of the trial's

prospectively defined secondary end points, which generally were composites of serious clinical events.

Featured discussant Dr Harvey White (Green Lane Hospital, Auckland, New Zealand) lauded ATOLL as "a contemporary

trial—in fact, a supercontemporary trial&mdash in terms of the use of radial access and the high rate of use of evidence-

based therapies. They've shown that enoxaparin is safe and may have an important clinically relevant effect on ischemic

end points in patients undergoing primary PCI." Still, he cautioned, "it missed its primary end point."

See ATOLL seen as supporting enoxaparin over standard heparin in primary PCI for more information.

COPPS (Colchicine for the Prevention of the Postpericardiotomy Syndrome)

Results: The first large-scale double-blind, placebo-controlled

trial to test the efficacy of colchicine to prevent the

development of postpericardiotomy syndrome (PPS) after

heart surgery has shown that the drug is very effective, with

only eight people needing to be treated to prevent one from

developing the syndrome.

See Colchicine halves incidence of postpericardiotomy

syndrome for more information.

RESPONSE (Randomized Evaluation of Secondary Prevention by Outpatient Nurse Specialists)

Results: A program of appointments with outpatient nurse

specialists was "reasonably successful" at lowering

cardiovascular risk on top of high-level usual care in patients

with acute coronary syndrome (ACS) in a randomized trial

conducted in the Netherlands. Patients who saw the nurses

four times over the six months after their event were more

likely to achieve targets for systolic blood pressure, LDL

cholesterol, and a healthy lifestyle, with a relative risk

reduction of 16.9% (p=0.029) in the primary outcome—

calculated 10-year mortality—after one year, compared with

the usual-care group. They did not, however, fare better in

terms of smoking cessation and or lose any more weight than

those getting standard care.

"I consider this trial extremely important," said American

College of Cardiology president Dr Ralph Brindis (Kaiser

Permanente, Oakland, CA), who attended the press

conference on the hot-line sessions. "We have to figure out a

better way of translating our science to the bedside. Here we

have a trial that shows an effective way of better delivering

care with things that we know work."

See Nurse program provides good RESPONSE for ACS

secondary prevention for more information.

STAR-heart

Results: The largest clinical trial so far of intracoronary

autologous stem-cell transplantation in patients with chronic

heart failure has shown that such treatment was associated

with multiple hemodynamic and functional benefits as well as a

reduction in mortality, benefits that were maintained out to five

years of follow-up. Results at three months, 12 months, and

five years after bone-marrow-cell therapy showed significant

improvement in left ventricular ejection fraction, cardiac index,

exercise capacity, oxygen uptake, and left ventricular

contractility. Controls, however, showed a deterioration in LV

performance.

"Our study suggests that, when administered as an alternative

or in addition to conventional therapy, bone-marrow-cell

therapy can improve quality of life, increase ventricular

performance, and increase survival. Intracoronary therapy has

been shown to be effective in acute myocardial infarction, and

the STAR-heart study now indicates its efficacy in chronic

heart failure," concluded presenter Dr Bodo-Eckehard

Strauer (Heinrich-Heine University, Düsseldorf, Germany).

See STAR-heart study: Stem cells associated with improved

long-term hemodynamics and reduced mortality in chronic

heart failure for more information.

Opinions from ESC

Heartfelt with Dr Melissa Walton-Shirley

STAR-heart study associates stem cells with improved hemodynamics

and reduced mortality; PEARL-HF on reducing hyperkalemia in heart

failure; SHIFT; Alpha Omega; HEBE III; and analysis of top news from

ESC 2010

Novel antiplatelets; optimal heparin dosing in ISAR-REACT 3A;

elinogrel, a new antiplatelet, passes test in INNOVATE PCI; ATOLL;

LESSON-1; ART trial; and analysis of top news from ESC 2010

ANTIPAF: Olmesartan doesn't suppress paroxysmal atrial fib;

AVERROES: Apixaban gives significant reductions in stroke; DANPACE;

FUTURA/OASIS-8; and analysis of top news from ESC 2010

Trials and PIs with Dr Michael Gibson

Heart failure and transplantation with Dr Ileana Piña

Focus on exercise in older men and in women at ESC 2010

Private practice with Dr Seth Bilazarian

Apixaban in AVERROES points the way to excellent alternatives to

warfarin

The Bob Harrington Show

Episode #27: Elinogrel and INNOVATE PCI with Dr Sunil Rao

Click here to view more opinions from ESC 2010

ESC Congress 2010: An Overview

Spotlight on Coronary Artery Disease: From Genes to

Outcomes

In an ESC press release, Prof Fausto Pinto, outgoing chair of

the Congress Program Committee, declared the meeting a

great success.

Attendance included: • 22 032 active participants

• 4947 exhibitors

• 571 accompanying persons

• 556 members of the press

The ESC Congress 2011 will be held in Paris on August 27-31,

2011. The spotlight will be: "Controversies in Cardiology."

For more information

ESC Coverage on theheart.org

http://www.theheart.org/coverage/esc-2010.do

Medscape ESC 2010

http://www.medscape.com/viewcollection/31520

ESC Congress 2010

http://www.escardio.org/congresses/esc-

2010/Pages/welcome.aspx

Credits and disclosures

Contributor Information

Shelley Wood

Managing Editor, heartwire

theheart.org

Kelowna, BC

Disclosure: Shelley Wood has disclosed no relevant

financial relationships.

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.

theheart.org is the leading online source of independent cardiology news.

We are the top provider of news and opinions for over 100 000 physicians.

Become a member of http://www.theheart.org

Become a fan on Facebook: http://www.facebook.com/theheartorg

Follow us on Twitter: http://www.twitter.com/theheartorg