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, TACT, UMPIRE, PHS II, OPERA and FORWARD, ASPIRE, TRILOGY ACS/ARCTIC, MADIT-RIT, RELAX-AHF, POSEIDON / SCIPIO, PCSK9 studies, PCSK9, dal-OUTCOMES andLoDoCo.

1. AHA 2012 research highlights:
A slideshow presentation

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. For more information
Complete AHA 2012 coverage on
theheart.org
AHA 2012 Scientific Sessions
American Heart Association

17. Credits and disclosures
Editor: Michael O'Riordan, heartwire
Shelley Wood theheart.org
Managing Editor, heartwire Toronto, ON
theheart.org Disclosure: Michael O'Riordan has
Kelowna, BC disclosed no relevant financial
Disclosure: Shelley Wood has disclosed relationships.
no relevant financial relationships.
Steve Stiles, heartwire
Journalists:
theheart.org
Sue Hughes, heartwire
Fremont, CA
theheart.org
Disclosure: Steve Stiles has disclosed no
London, UK
Disclosure: Sue Hughes has disclosed
relevant financial relationships.
no relevant financial relationships.
Contributors:
Reed Miller, heartwire Steven Rourke
theheart.org Editorial Director
State College, PA theheart.org
Disclosure: Reed Miller has disclosed Montreal, QC
no relevant financial relationships. Disclosure: Steven Rourke has disclosed
no relevant financial relationships.
Lisa Nainggolan, heartwire
theheart.org Maria Turner
London, UK Montreal, QC
Disclosure: Lisa Nainggolan has Disclosure: Maria Turner has disclosed no
disclosed no relevant financial relevant financial relationships.
relationships.

18. 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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