AHA 2011 research highlights:

A slideshow presentation

AHA 2011 Research Highlights

The American Heart Association (AHA) 2011 Scientific Sessions

took place in Orlando, FL, from November 12 through November 16,

2011.

Key trials presented at the sessions include:

AIM-HIGH: Stopped early at three years due to unexplained increase

in ischemic stroke in the niacin group vs placebo; experts now say

trial should not have stopped

SATURN: High-dose statin therapy resulted in significant regression

of coronary atherosclerosis

ATLAS: Rivaroxaban 2.5 mg has shown promising results

ELEVATE: Clopidogrel 225 mg for patients with one loss-of-function

allele

PALLAS: Dronedarone a hazard in high-risk CV patients with permanent AF

TRACER: Novel thrombin blocker vorapaxar stumbles in ACS, ups bleeding risk

POWER: Phone and internet intervention achieves and maintains weight loss

FAST: Surgical ablation bests catheter ablation in treatment of drug-refractory AF

C-PORT E: Elective PCI doesn't require surgical backup

MI FREEE: Cutting copays for post-MI drugs helps outcomes, with no added cost to insurers

ADOPT: Extended apixaban no better than standard enoxaparin for VTE in medically ill

NHBLI: NHBLI-appointed expert panel recommends universal cholesterol screening for kids

AIM-HIGH

Stopped early at three years due to unexplained increase in

ischemic stroke in the niacin group vs placebo; experts

now say trial should not have stopped

Results: Final results of the AIM-HIGH trial appear to suggest

that the signal of increased ischemic stroke with niacin, which

was one of the reasons the study was stopped early, could have

been the play of chance, with the final p value for ischemic

stroke coming in at a nonsignificant 0.11. This has provoked a

backlash from researchers in the field against the National

Institutes of Health (NIH) sponsors of the study who made the

decision to terminate the trial.

"When the NIH stopped the trial, there was an increase in ischemic stroke of borderline significance," said lead investigator

Dr William Boden (University of Buffalo School of Medicine, NY). "I think they saw neutral outcome data, and because of

a potential ethical safety issue they decided to stop the trial. But there was no signal of an increase in fatal stroke or of all-

cause or cardiac mortality. And now that we have all the data, the effect is far from significant, and when we look just at

strokes that occurred when the patients were actually on treatment, we have 21 on niacin vs 18 on placebo. The earlier

numbers were clearly an aberration—just the play of chance."

See: AIM-HIGH: Results raise controversy over early stopping

SATURN

High-dose statin therapy resulted in significant regression

of coronary atherosclerosis

Results: High-dose statin therapy with atorvastatin or

rosuvastatin resulted in a significant regression of coronary

atherosclerosis in the SATURN trial, despite differential effects

on LDL- and HDL-cholesterol levels with the two most popular

lipid-lowering medications. Treatment with rosuvastatin 40 mg

resulted in lower LDL- and higher HDL-cholesterol levels than

atorvastatin 80 mg, but the effect on percent atheroma volume

(PAV) measured by intravascular ultrasound (IVUS) did not

significantly differ. Less than 5% of patients with stable coronary

disease are treated with maximum-dose statins, and this

remains one of the challenges in secondary prevention.

"We're very good at prescribing statins, we're just not so good at increasing the doses," said Dr Stephen Nicholls

(Cleveland Clinic, OH). "Safety is one of the elements of it, but the other element is that people question what the added

benefit is. The incremental LDL lowering is about 5% or 6% every time you double the dose. I think what we're seeing here

is very reassuring for patients. Over a 24-month period, patients with largely stable disease tolerated these agents very

well at these doses. They achieved very effective levels of LDL and HDL cholesterol, and if you're looking for benefit, I see

the removal of the disease from the artery wall that ultimately causes the clinical event as a very reassuring extra benefit

for the doses of these agents."

See: SATURN: Maximum doses of rosuvastatin and atorvastatin equally regress atherosclerosis

ATLAS

Rivaroxaban 2.5 mg has shown promising results, with a

reduction in overall and cardiovascular mortality vs placebo,

despite an increased risk of bleeding and ICH

Results: The lower of the two doses of the new oral anticoagulant

rivaroxaban tested in the ATLAS ACS 2 TIMI 51 trial has shown

promising results, with a reduction in overall and cardiovascular

mortality vs placebo, despite an increased risk of bleeding and

intracranial hemorrhage (ICH). The trial compared two doses of

rivaroxaban with placebo in ACS patients. All patients were taking

low-dose (75-100 mg) aspirin and 93% were also on clopidogrel.

Study treatment was started an average of 4.6 days after the ACS

event. Patients with a previous stroke or transient ischemic attack

(TIA) were excluded, as this group has been shown to have a

particularly high risk of ICH in previous trials of other antithrombotic

agents. The population was high risk, with half having had a STEMI.

Both rivaroxaban doses reduced the primary end point of cardiovascular death/MI/stroke, at the cost of increased bleeding rates. The 2.5-

mg twice-daily dose had the better benefit/risk balance, due to a lower bleeding risk than the 5-mg twice-daily dose.

"Thus, the addition of very low-dose anticoagulation with rivaroxaban may represent a new treatment strategy in patients with a recent

acute coronary syndrome," the ATLAS investigators conclude in the New England Journal of Medicine paper, published online to coincide

with the AHA presentation. "We have shown a 32% relative reduction in all-cause mortality with the 2.5-mg dose in the whole population

and a 36% reduction in those on dual antiplatelet therapy. This translates into one death prevented for every 56 patients treated for two

years. This is big news," said ATLAS investigator Dr Michael Gibson (Beth Israel Deaconess Hospital, Boston, MA).

See: ATLAS ACS 2: Low-dose rivaroxaban looks good in ACS

ELEVATE-TIMI 56

Tripling the maintenance dose of clopidogrel in stable

heart disease patients carrying one clopidogrel loss-of-

function allele achieved levels of platelet reactivity similar

to that seen with the standard dose in noncarriers

Results: The ELEVATE-TIMI 56 trial results show that tripling

the maintenance dose of clopidogrel to 225 mg daily in stable

heart disease patients carrying one clopidogrel loss-of-function

allele (CYP2C19*2) achieved levels of platelet reactivity similar

to that seen with the standard 75-mg dose in noncarriers. In

contrast, in patients with two loss-of-function alleles, doses as

high as 300 mg daily did not result in comparable degrees of

platelet inhibition.

"If I knew someone's genotype [indicated loss of function], I would feel uncomfortable treating them with standard doses of clopidogrel,"

said Dr Jessica Mega (Brigham and Women's Hospital, Boston, MA), adding that there are also other agents available, prasugrel and

ticagrelor, that have been shown to reduce events in "all-comers." That's despite the fact that ELEVATE did not look at effects on patient

outcomes. "It is important to understand that this is a pharmacodynamic study . . . but I think it gives us a great deal of insight into the

optimal ways of treating different patients with clopidogrel."

See: ELEVATE-TIMI 56: Clopidogrel 225 mg for patients with one loss-of-function allele

PALLAS

Dronedarone a hazard in high-CV-risk patients with

permanent AF

Results: The PALLAS data indicate that the dronedarone-

related CV events over a median follow-up of 3.5 months

consisted largely of stroke, heart failure, CV death, and

arrhythmic death. Those events contributed to significant

increases, by a factor of about two, in the trial's pair of co–

primary end points: stroke, MI, systemic embolism, or CV

death; and death or unplanned CV hospitalization. The

significant effect of dronedarone on those end points held

regardless of NYHA functional class or LVEF. The PALLAS

results were published in the New England Journal of Medicine,

coinciding with their presentation at AHA 2011.

"Our data show that dronedarone is hazardous in such patients," write the publication's authors, led by Dr Stuart J

Connolly (Population Health Research Institute and McMaster University, Hamilton, ON). "It is reasonable to conclude that

dronedarone should be avoided in patients with heart failure and other advanced cardiovascular disease, particularly when

they also have permanent atrial fibrillation."

See: PALLAS: Dronedarone a hazard in high-CV-risk patients with permanent AF

TRACER

Novel thrombin blocker vorapaxar stumbles in ACS, ups

bleeding risk

Results: In the international TRACER trial with >12 000 patients

with non-ST-elevation ACS who were mostly already on dual-

agent antiplatelet therapy, adding the investigational

antithrombotic agent vorapaxar to standard therapy

significantly raised the risk of major bleeding complications,

including intracranial hemorrhage (ICH), over two years. That

wasn't a complete surprise, as TRACER had been halted earlier

this year when an interim safety analysis saw a jump in ICH

among vorapaxar patients with a history of stroke.

"The magnitude of the increase [in bleeding] was not expected on the basis of preclinical and phase 2 data" for [protease-

activated receptor 1] PAR-1 blockade, which suggested no risk increase when added to aspirin and clopidogrel, TRACER

investigators write in the New England Journal of Medicine, where their report was published online to coincide with its

scheduled presentation here at the AHA sessions.

However, they continue, "The results from our study are consistent with previous evidence indicating that more potent

antithrombotic therapy incrementally increases the risk of bleeding."

See: TRACER: Novel thrombin blocker vorapaxar stumbles in ACS, ups bleeding risk

POWER

Phone and internet intervention achieves and maintains

weight loss

Results: The randomized, two-year POWER trial showed that a

weight-loss program conducted solely by telephone and via

internet was just as effective as a program attended in person,

with face-to-face coaching, at promoting meaningful weight loss

and helping to keep it off.

About half of the patients participating in either weight-loss

intervention lost at least 5% of their initial body weight (the

primary end point) within six months. The lost weight stayed off

after two years in about 40% of both groups. The degree of

weight loss achieved was similar to that of other weight-loss

studies.

"In contrast with the findings in most weight-loss trials, however, participants sustained weight loss to the end of the trial,"

according to lead author Dr Lawrence J Appel (Johns Hopkins University, Baltimore, MD).

See: POWER program: Phone, internet intervention achieves, maintains weight loss

FAST

Surgical ablation bests catheter ablation in treatment of

drug-refractory AF

Results: The FAST trial was a randomized comparison between

surgical ablation and radiofrequency catheter ablation for the

treatment of antiarrhythmic-drug–refractory atrial fibrillation. It

showed that the surgical approach is superior in achieving

freedom from arrhythmias at one year. The minimally invasive

surgical approach is not without its drawbacks, however, with

investigators reporting a significantly higher procedural adverse-

event rate in the surgical ablation arm compared with catheter

ablation. Of note, 67% of the patients included in the trial had

failed a previous catheter-ablation procedure, "which could

signify a predisposition to catheter-ablation failure."

"In this population of patients with atrial fibrillation with dilated left atrium and hypertension who had failed a prior catheter

ablation, we found that minimally invasive surgical ablation was superior to catheter ablation to achieve freedom from atrial

arrhythmias without antiarrhythmic drugs in follow-up to 12 months," said lead investigator Dr Lucas Boersma (St

Antonius Ziekenhuis, Nieuwegein, the Netherlands) during a press conference announcing the results. "Surgical ablation

was accompanied by a higher adverse-event rate than catheter ablation, and we think this is important for physicians and

patients when deciding which type of invasive therapy they need."

See: FAST: Surgical ablation bests catheter ablation in treatment of drug-refractory AF

C-PORT E

Elective PCI doesn't require surgical backup

Results: During a late-breaking clinical-trial session, findings

from the C-PORT E trial showed that patients who had elective

PCI at experienced US hospitals without on-site cardiac surgery

fared no worse than those who had the same procedure at

institutions with surgical backup. The mortality rate after six

weeks was almost the same for each group, at just under 1%.

"The key finding is that the patient-related medical outcomes, at least the short-term safety outcomes, of elective

angioplasty are the same, regardless of the hospital type," said Dr Thomas Aversano (Johns Hopkins Medical Institute,

Baltimore, MD). He added that his team will have data on how patients fared nine months after the procedure early next

year. And he stressed: "The purpose of the trial was not to expand the number of centers doing angioplasty but to give

healthcare policy makers—who can make rational decisions about access, quality, and cost of angioplasty care in their

state—some information on which to base their decision."

See: C-PORT E: Elective PCI doesn't require surgical backup

MI FREEE

Cutting copays for post-MI drugs helps outcomes, with no

added cost to insurers

Results: The 5855-patient MI FREEE study shows that patients

who had suffered an MI were significantly less likely to have

another major cardiac event if the costs of statins, beta

blockers, ACE inhibitors, and angiotensin-receptor blockers

were totally covered by insurance rather than if their insurance

company charged them a copay for their drugs. For the primary

outcome of revascularization plus major cardiac events

combined, the difference was not statistically significant. The

patients with no copay paid 26% less overall for their drugs than

the patients with copays. Over the three years of follow-up, the

people with no copay actually cost the insurance company

slightly less to care for than the people with one ($66 008 vs

$71 778; p=0.68).

"For essential medications—the meds we're talking about are highly evidence-based—we don't want people to stop using

those meds when the copays are a relatively small part of cost relative to costs of hospitalizations, or even death, that

result from not using the drugs," said study lead author Dr Niteesh Choudhry (Harvard University, Boston, MA). Not only

does eliminating copays not cost the insurance company more in the long run, it's also an easy change to implement,

Choudhry said. "Insurers that want to do this could do this tomorrow. It literally just means changing pharmacy

authorization codes. It doesn't mean deploying armies of nurse health coaches or anything like that."

See: Cutting copays for post-MI drugs helps outcomes, with no added cost to insurers

ADOPT

Extended apixaban no better than standard enoxaparin for

VTE in medically ill

Results: Results of the ADOPT trial demonstrate that

prolonging prophylaxis for venous thromboembolism in

medically ill patients with a 30-day course of the new oral

anticoagulant apixaban was not superior to a shorter six- to 14-

day course of subcutaneous enoxaparin—designed to

represent standard in-hospital VTE prevention.

"The ADOPT trial does not provide evidence to justify a policy of extended prophylaxis in a broad population of medically ill

patients after hospital discharge," said Dr Samuel Z Goldhaber (Brigham and Women's Hospital, Boston, MA) in a press

conference at the AHA meeting. However, the ADOPT findings, together with those from similar studies—such as the

MAGELLAN trial with rivaroxaban and EXCLAIM with enoxaparin—show that "it is clear that the risk of VTE increases

beyond the time of hospital discharge" in this patient population.

See: ADOPT: Extended apixaban no better than standard enoxaparin for VTE in medically il

NHBLI-appointed expert panel recommends universal cholesterol screening for kids

Results: The Expert Panel on Integrated Guidelines for

Cardiovascular Health and Risk Reduction in Children and

Adolescents presented new guidelines at the AHA meeting.

They recommended that all children, regardless of family

history, undergo universal screening for elevated cholesterol

levels. The panel recommended that adolescents undergo lipid

screening for nonfasting non-HDL-cholesterol levels or a fasting

lipid panel between the ages of 9 and 11 years followed by

another full lipid screening test between 18 and 21 years of age.

They also recommend measuring fasting glucose levels to test

for diabetes in children 10 years of age (or at the onset of

puberty) who are overweight with other risk factors, including a

family history, for type 2 diabetes mellitus.

The Expert Panel was appointed by the National Health, Lung,

and Blood Institute (NHLBI) and endorsed by the American

Academy of Pediatrics (AAP).

"The goal of the expert panel was to develop comprehensive evidence-based guidelines that address the known risk factors

for cardiovascular disease to assist all primary pediatric care providers in both the promotion of cardiovascular health and the

identification and management of specific risk factors from infancy into young adult life," write panel chair Dr Stephen Daniels

(University of Colorado School of Medicine, Denver) and colleagues in Pediatrics.

See: NHBLI-appointed expert panel recommends universal cholesterol screening for kids

For more information

Complete AHA 2011 coverage on

theheart.org

AHA 2011 Scientific Sessions

American Heart Association

Credits and disclosures

Editor:

Shelley Wood

Managing Editor, heartwire

theheart.org

Kelowna, BC

Disclosure: Shelley Wood has disclosed no relevant financial relationships.

Contributors:

Steven Rourke

Manager, Editorial programming theheart.org

Montreal, QC

Disclosure: Steven Rourke has disclosed no relevant financial relationships.

Katherin Vasilopoulos

Montreal, QC

Disclosure: Katherin Vasilopoulos has disclosed no relevant financial

relationships.

Journalists:

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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