AHA 2012 research highlights:

A slideshow presentation

AHA 2012 Research Highlights

The American Heart Association (AHA) 2012 Scientific Sessions

took place in Los Angeles, CA on November 3-7, 2012.

Key trials presented at the sessions include:

FREEDOM: CABG superior to PCI in diabetic patients with coronary

disease

TACT: Surprising, puzzling benefit from chelation therapy after MI

UMPIRE: Fixed-dose combo improves adherence, lowers cholesterol

and BP

PHS II: No benefits of vitamins for preventing CVD

OPERA and FORWARD: Death knell for fish oil in atrial fibrillation

ASPIRE: Aspirin good option for extended treatment of VTE

TRILOGY ACS/ARCTIC: Back to the drawing board for platelet monitoring

MADIT-RIT: Simple programming change averts most inappropriate ICD therapy

RELAX-AHF: Serelaxin reduces dyspnea, but questions surround mortality benefit

POSEIDON / SCIPIO: Two trials stand out among the mixed results of stem-cell trials presented at the Scientific Sessions

PCSK9 studies: Two new PCSK9 MAbs for LDL-lowering look good in phase 2

dal-OUTCOMES: Wrestling with why the CETP inhibitor failed to reduce outcomes

LoDoCo: Cheap, widely available colchicine reduces events in secondary prevention

FREEDOM

CABG superior to PCI in diabetic patients with coronary

disease

Results: Patients with diabetes and multivessel coronary artery

disease treated with CABG surgery had significantly lower rates

of death from any cause, nonfatal MI, or nonfatal stroke when

compared with diabetic patients treated with PCI, according to

the long-awaited main results of the FREEDOM trial. The

researchers believe the results have the potential to

immediately alter clinical practice and potentially have an

impact on the clinical guidelines for the management of patients

with diabetes.

"I think the study is very convincing, and I think the guidelines will likely recognize that," said Dr David Williams (Brigham

and Women's Hospital, Boston, MA), an interventional cardiologist not affiliated with the trial. "There have been trends

showing this before, such as the BARI-2D study with similar information showing that surgery was definitely better than

medicine. I think that if you look at the anatomy—and all coronary disease is not the same—the anatomy [of diabetics] is

imposing, and I think most of these patients go to surgery anyway. But I think this provides meaningful information to help

us with these decisions."

See:

FREEDOM: CABG superior to PCI in diabetic patients with coronary disease

TACT

Surprising, puzzling benefit from chelation therapy after MI

Results: A randomized, double-blind trial of chelation therapy

has suggested that the alternative-medicine mainstay may

modestly improve clinical outcomes in patients after an acute

MI. Over a four-year follow-up, those who followed an arduous

regimen involving up to 40 separate three-hour infusions of a

standard chelation-therapy solution of multiple ingredients,

compared with a placebo, showed an 18% drop in the trial's

primary end point. Adverse effects were mostly minimal. The

difference in the end point—a composite of all-cause mortality,

MI, stroke, coronary revascularization, and hospitalization for

angina—barely reached the trial's prespecified threshold for

statistical significance.

Dr E Magnus Ohman (Duke University, Durham, NC), who wasn't connected with the trial, agreed that the efficacy

difference was only marginal but pointed to the trial's subgroup analysis, which suggested that diabetics seemed to show a

significantly more pronounced benefit from chelation therapy than the population as a whole. "So there's a subgroup that

appears to have a very strong signal."

See:

TACT: Surprising, puzzling benefit from chelation therapy after MI

UMPIRE

Fixed-dose combo improves adherence, lowers cholesterol

and BP

Results: A fixed-dose combination tablet that includes aspirin, a

statin, and two antihypertensive medications improves

adherence to therapy and results in a significant reduction in

LDL-cholesterol levels and blood pressure when compared with

patients randomized to usual care. Overall, investigators

observed a 33% increase in adherence over a 15-month period,

suggesting that fixed-dose combination therapy might go a long

way toward reducing cardiovascular events in this population of

high-risk patients and those with established cardiovascular

disease.

"I think the real potential benefit in UMPIRE is compliance, giving everybody a single pill that is easier to take, rather than a

handful of pills," said Dr Dariush Mozaffarian (Brigham and Women's Hospital, Boston, MA). "I think, on average, that's

actually a good idea. If people have indications for these medicines, why not combine them into a single pill and make it

easier for them to take? I think the polypill is a good idea for people who already have the indications."

See:

UMPIRE's ruling: Fixed-dose combo improves adherence, lowers cholesterol and BP

PHS II

No benefits of vitamins for preventing CVD

Results: The largest, randomized, double-blind trial to date has

confirmed what smaller studies have suggested and what many

physicians have long believed: a daily multivitamin does not

reduce the risk of CVD.

In an accompanying editorial, Dr Eva Lonn (McMaster

University, Hamilton, ON) notes that over one-third of the US

population takes some kind of daily multivitamin, swelling sales

of dietary supplements to almost $24 billion in 2008.

Regulations governing their approval and marketing, however,

are less strict than for drugs. "This has allowed for claims of

benefit in preventing or curing an amazingly diverse and ever-

increasing variety of illnesses ranging from CVD to cancer,

arthritis, infections, macular degeneration, Alzheimer's disease, wrinkles, hair loss, decreased libido, and low sexual

prowess. As a result," she argues, "many people with heart disease or risk factors continue to lead unhealthy lives yet

take daily vitamins and supplements in the hope of mitigating future problems."

See:

Big bucks, no bang: PHS II shows no benefits of vitamins for preventing CVD

OPERA and FORWARD

Death knell for fish oil in atrial fibrillation

Results: Short-term administration of fish oil to patients

undergoing heart surgery did not reduce the incidence of

postoperative atrial fibrillation (AF) according to the results of

the OPERA trial. There was no difference between the active-

treatment and placebo groups in terms of preventing

postoperative AF, despite the fact that patients in this study

were given fairly high doses of fish oil in the form of a

prescription product. This assertion was borne out in a second

trial, Fish Oil Research with Omega-3 for Atrial Fibrillation

Recurrence Delay (FORWARD), performed in people with

previous AF, to see whether 1 g per day of fish oil would prevent

recurrences. It did not.

"Every time we've had a major trial using omega-3s that was

conducted as a primary purpose of the trial, we've come up

short. It's very discouraging for the omega-3 story," said invited

panel member Dr Peter Wilson (Emory University, Atlanta).

See:

OPERA does not sing praises for fish oil in AF

ASPIRE

Aspirin good option for extended treatment of VTE

Results: People who have suffered a first episode of

unprovoked venous thromboembolism (VTE) need to have

initial therapy with heparin followed by warfarin or one of the

newer anticoagulants for a few months, but thereafter there is

debate as to what they should do. Results of a new study—

together with findings from an almost identical trial reported last

year, WARFASA—now suggest that 100 mg per day of aspirin

is a good option for ongoing treatment in these patients.

"We are not advocating that patients should decide to stop anticoagulant therapy early as a result of these findings,"

stresses senior author Dr John Simes (University of Sydney, Australia). "But in patients who are going to stop anyway,

aspirin provides a moderately effective treatment compared with not having anything. We believe this is a cheap and

relatively safe therapy that should be considered to prevent further venous thromboembolic events, and not only is it of

benefit in clinical terms, but it is cost saving."

See:

ASPIRE: Aspirin good option for extended treatment of VTE

TRILOGY ACS and ARCTIC

Back to the drawing board for platelet monitoring

Results: The role of platelet-function monitoring has suffered

another serious setback, with two new studies adding to several

others that suggest no benefit of such an approach.

The TRILOGY ACS substudy found no independent association

of platelet function and ischemic outcomes in medically

managed ACS patients. Meanwhile, the ARCTIC trial found no

benefit of platelet-function testing and modification of treatment

in patients receiving drug-eluting stents.

"The TRILOGY substudy tells us that this single marker measuring ADP-mediated platelet activation is not giving us the

whole picture," said senior TRILOGY investigator Dr E Magnus Ohman (Duke Clinical Research Institute, Durham, NC).

"It is more complicated than that. There are six or seven different receptors on platelets, and we have just measured

one." Commenting on the ARCTIC study, he added: "I don't think this means that monitoring is not a viable strategy in

selected patients, but we may need to do much more work to understand what affects platelet reactivity that is driven by

common clinical characteristics."

See:

TRILOGY/ARCTIC: Back to the drawing board for platelet monitoring

MADIT-RIT

Simple programming change averts most inappropriate

ICD therapy

Results: A large randomized trial has identified specific

programming criteria for implantable cardioverter defibrillator

(ICD) devices that, compared with conventional programming,

cut the risk of inappropriately delivered therapy by almost 80%.

The alternate programming also led to a significant drop in

mortality in the patients with primary-prevention ICDs by more

than one-half over a follow-up averaging 1.4 years.

"It would have been very surprising to me if this had not been a positive study, but what we didn't have before was a

large, randomized clinical trial," said Dr Bruce L Wilkoff (Cleveland Clinic, OH). "This is a large randomized trial that

supports absolutely all the studies that have come before it, with a large and clearly significant outcome. So I think this is

huge."

See:

MADIT-RIT: Simple programming change averts most inappropriate ICD therapy

RELAX-AHF

Serelaxin reduces dyspnea, but questions surround

mortality benefit

Results: A novel recombinant form of human relaxin 2 used in

the treatment of acute heart failure (AHF) reduced shortness of

breath as assessed using one of two dyspnea end points,

according to the results of a new study. Investigators were also

excited by the reduction in all-cause and cardiovascular

mortality with serelaxin (Novartis Pharmaceuticals), as well as

reductions in the signs and symptoms of congestion and

worsening heart failure.

"In terms of its primary end point, breathlessness, I think there is little doubt that this agent was beneficial," said Dr John

McMurray (University of Glasgow, Scotland). "The totality of the evidence, the breathlessness measurement, the signs,

the symptoms, and the use of other therapies, to me at least, quite clearly indicate that this drug is doing something good

in terms of relief of symptoms and congestion."

See:

RELAX-AHF: Serelaxin reduces dyspnea, but questions surround mortality benefit

POSEIDON and SCIPIO

POSEIDON: Allogeneic stem cells are safe in chronic ischemics;

SCIPIO: Cardiac stem cells reverse heart failure

Results: Results of the POSEIDON study indicate that myocardial

injections of allogeneic mesenchymal stem cells (MSC) are safe and may

eventually be an "off-the-shelf" therapy for chronic ischemic MI. As well,

encouraging two-year follow-up results from SCIPIO, a small study of

cardiac stem-cell (CSC) injections in patients with ischemic

cardiomyopathy, showed that the CSC-treated patients had statistically

significant improvements in mass of nonviable myocardial tissue and the

percentages of viable tissue within the infarcted region. Minnesota Heart

Failure Scores improved significantly in the CSC-treated patients while

remaining almost flat in the control group.

"We come away from this [trial] with optimism and feel that we've helped to define the parameters around which cell therapy can and

should be used for ischemic cardiomyopathy," said lead POSEIDON investigator Dr Joshua Hare (University of Miami, FL).

"We are just at the beginning of a dramatic revolution in cardiovascular medicine," said Dr Roberto Bolli (University of Louisville,

KY). "It's amazing. We picked an arbitrary dose. We don't understand when the best time to give [the cells] is or if you can give them

multiple times to the same patient—which we probably can, but it hasn't been done so far—so we're still learning how to use them,

but the very first time with this totally new therapy we found such a dramatic improvement. This is very encouraging."

See:

POSEIDON: Allogeneic stem cells are safe in chronic ischemics

SCIPIO: Cardiac stem cells reverse heart failure

PCSK9 studies

New PCSK9 MAbs for LDL-lowering look good in phase 2

Results: New phase 2 studies with two anti-PCSK9 monoclonal

antibodies all show large reductions in LDL cholesterol. The

antibodies work by inhibiting the PCSK9 protein. This PCSK9

protein binds to LDL receptors, resulting in their degradation, so

that fewer are available on liver cells to remove excess LDL-C

from the blood. Moreover, traditional LDL-lowering therapies

such as statins actually stimulate the production of PCSK9,

which limits their own ability to lower LDL-C. By blocking the

PCSK9 pathway, these antibodies upregulate the recycling of

LDL receptors and therefore represent a potentially novel

mechanism for lowering LDL.

Dr Peter Wilson (Emory University School of Medicine, Atlanta) said the information presented today added data on anti-

PCSK9 antibodies in another 450 to 500 patients. "We now have biologics now to treat hypercholesterolemia. The lipid

effects with these antibodies are really quite good. They are very effective and extremely promising." But he added: "All

eyes will now be on safety and long-term outcomes."

See:

Two new PCSK9 MAbs for LDL-lowering look good in phase 2

dal-OUTCOMES

Wrestling with why the CETP inhibitor failed to reduce

outcomes

Results: Final results of the dal-OUTCOMES study, a phase 3

clinical trial testing the efficacy of the investigational cholesteryl

ester transfer protein (CETP) inhibitor dalcetrapib (Hoffman-La

Roche), have left investigators to wrestle with reasons that the

drug failed to have an impact on clinical outcomes. Some

experts believe the modest but clinically significant increase in

blood pressure might have doomed the drug.

"It may be that when other risk factors are controlled as well as we currently can using many, if not all, of our evidence-

based treatments, including statins, dual antiplatelet therapies, beta blockers, etc, that the risk that's modifiable by altering

HDL-cholesterol levels may not be significant," said Dr Gregory Schwartz (University of Colorado School of Medicine,

Denver). He pointed out that even among patients in dal-OUTCOMES who achieved the highest HDL-cholesterol levels,

approximately 70 mg/dL in about 10% of patients, there was no apparent decrease in risk compared with other patients in

the trial.

See:

dal-OUTCOMES: Wrestling with why the CETP inhibitor failed to reduce outcomes

LoDoCo

Cheap, widely available colchicine reduces events in

secondary prevention

Results: In this prospective, randomized, open, blinded end-

point study testing the effectiveness of colchicine in secondary

prevention, investigators showed that the drug reduced the risk

of the primary end point—defined as ACS, out-of-hospital

cardiac arrest, or noncardioembolic ischemic stroke—by 67%,

driven largely by a reduction in non–stent-related ACS.

Colchicine is an old drug commonly used to treat gout and

familial Mediterranean fever.

Dr Seth Bilazarian (Pentucket Medical Associates, Haverhill,

MA) said he was very excited to see such positive results for an

old standby. "Our familiarity and longtime use of this drug in

gout makes this a very attractive treatment option."

See:

LoDoCo: Cheap, widely available colchicine reduces events in

secondary prevention

For more information

Complete AHA 2012 coverage on

theheart.org

AHA 2012 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.

Journalists:

Sue Hughes, heartwire

theheart.org

London, UK

Disclosure: Sue Hughes has disclosed

no relevant financial relationships.

Reed Miller, heartwire

theheart.org

State College, PA

Disclosure: Reed Miller has disclosed

no relevant financial relationships.

Lisa Nainggolan, heartwire

theheart.org

London, UK

Disclosure: Lisa Nainggolan has

disclosed no relevant financial

relationships.

Michael O'Riordan, heartwire

theheart.org

Toronto, ON

Disclosure: Michael O'Riordan has

disclosed no relevant financial

relationships.

Steve Stiles, heartwire

theheart.org

Fremont, CA

Disclosure: Steve Stiles has disclosed no

relevant financial relationships.

Contributors:

Steven Rourke

Editorial Director

theheart.org

Montreal, QC

Disclosure: Steven Rourke has disclosed

no relevant financial relationships.

Maria Turner

Montreal, QC

Disclosure: Maria Turner has disclosed no

relevant financial relationships.

More slideshows

TCT 2012 research highlights

ESC 2012 research highlights

EuroPCR 2012 research highlights

HRS 2012 research highlights

ACC 2012 research highlights

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