American Heart Association Scientific Sessions 2011: Post-Game Show

by admin on November 21, 2011 has the pleasure of hosting the following post by contributing blogger, Dr. Richard Andraws MD, who is a Board Certified Cardiologist

Every year thousands of scientists and clinicians from around the globe converge on the American Heart Association’s annual Sessions to share their work, be it basic or patient-centered research. Some studies are intriguing fodder for further investigation while others significantly impact day-to-day practice. This year’s crop was no different. The following is a sampling of the more interesting and important. For more details and coverage, a link is provided at the bottom.


The fine folks of the Thrombolysis in Myocardial Infarction (TIMI) group at Harvard have been teaching us how to treat heart attacks for over 20 years. The TIMI series of trials has revolutionized our approaches and improved patient outcomes. A central strategy in current heart attack management is the use of blood thinners during initial hospitalization along with aspirin and a second antiplatelet agent (such as clopidogrel, known by the trade name Plavix). Antiplatelet drugs are continued after hospitalization, but despite a significant reduction in recurrent heart attacks, we haven’t been able to eliminate them completely.  ATLAS ACS 2-TIMI 51 was designed to answer the question, “What if we add a blood thinner after discharge from the hospital?”

Over 15,000 patients with recent heart attacks were randomized to antiplatelets plus placebo or antiplatelets plus rivaroxaban (2.5 mg or 5 mg twice daily).  Rivaroxaban is a Factor Xa inhibitor, a blood thinner that was recently shown to prevent strokes in patients with atrial fibrillation. Compared to placebo, rivaroxaban reduced death, heart attack and stroke by 16%. Major bleeding was significantly higher, however. There were no fatal bleeds, but there is increasing evidence that even nonfatal bleeds are bad in the long term. Exactly how rivaroxaban will fit into the picture is yet to be determined.


Angioplasty and stenting–also known as percutaneous coronary intervention (PCI)–has become the mainstay of fixing blockages in the coronary arteries in patients not needing bypass surgery. The procedure involves inserting a tiny balloon into the heart via an artery in the leg, inflating it to push the fatty plaque blocking blood flow against the vessel’s wall and leaving behind a fine metal mesh (the stent) as a scaffolding to keep things open. In the early days, particularly before stents were used, blowing up a balloon in a coronary sometimes caused more harm than good: those unfortunate patients required emergent bypass surgery. Thus, PCI was restricted to hospital that had surgeons on site—just in case.

But as technology and techniques have improved, PCI has become much safer with rare need for emergent surgery. So should it be less restricted? Should it be more available to patients at smaller, local hospitals? That’s what C-PORT E asked. The trial randomized nearly 19,000 patients to stenting at hospitals with on-site surgery and those without. Death and major complications were not significantly different (and were almost identical) between hospitals. This report was limited to the first 6 weeks after the procedure. Longer term data will soon be reported. It also examined elective and not emergent procedures. Based on the findings so far, things look promising for more widespread access to elective PCI.


We mentioned the PALLAS trial last August. Preliminary results released in July showed that the antiarrhythmic drug dronedarone (trade name Multaq) worsened outcomes in patients with “permanent” atrial fibrillation. This is the full report of the study. Dronedarone was approved by the FDA in 2009 to prevent hospitalization in patients with atrial fibrillation who were in normal rhythm while on the drug. This approval was based on the success of the ATHENA study. PALLAS asked the question: What about patients in atrial fibrillation while on the drug? Would they derive any benefit?

PALLAS planned to randomize over 10,000 patients, but only enrolled 3,326. It was stopped prematurely because of a increase in cardiovascular events (death, strokes and hospitalizations for heart failure) in those patients given dronedarone. Patients given the drug were about twice as likely to experience one of these outcomes. Based on this study, dronedarone should not be used in patients with chronic or permanent atrial fibrillation.


The benefits of lowering “bad” cholesterol (also known as LDL cholesterol has been proven repeatedly in the last 20 years. For every 1% decrease in LDL, there’s a 1% decrease in heart attack risk. But is LDL the whole story? There’s also evidence that higher levels of “good” cholesterol (HDL) may also confer protection from cardiovascular disease. The supplement niacin is the best medication we have currently to raise HDL levels.

AIM-HIGH asked whether adding niacin to treatment with simvastatin in patients with cardiovascular disease and low LDL (but also low HDL and high triglyceride levels) would further reduce risk of death, heart attack, stroke and hospitalization. It enrolled 3,414 patients and followed them an average of 36 months. The trial was stopped prematurely because of a trend toward increased combined events in patients treated with niacin. There was also a trend toward increased strokes. The precise reason for these findings is unclear as niacin has previously been shown to be a safe and effective medication. For now, there appears to be no incremental benefit (and possibly harm) in trying to increase HDL in patients with optimal levels of LDL.


In a related trial (previously covered on the blog), researchers attempted to show that lowering LDL cholesterol with a more potent medication (rosuvastatin, also known as Crestor) when compared to a “standard” (atorvastatin, known as Lipitor) would result in measurable structural changes in diseased blood vessels. LDL cholesterol is the central player in arterial plaque buildup.

SATURN randomized approximately 1400 patient to maximum doses of rosuvastatin or atorvastatin for 2 years. Over this period, plaque buildup in one of their coronary arteries was serially assessed through catheterization and assessment with intravascular ultrasound (IVUS). While rosuvastatin significantly decreased LDL versus atorvastatin and significantly raised HDL, it was no more effective at decreasing plaque build-up. It’s likely that the marginal incremental benefit of rosuvastatin on the numbers versus a very effective comparator was not enough to translate into significant physical changes. Nonetheless, both medications will remain very important weapons in our armamentarium against bad cholesterol and cardiovascular disease.

The Return of the CETP Inhbitors

The cardiovascular medicine world was anxiously awaiting this new class of drugs several years ago with the development of the first member, torcetrapib. The CETP inhibitors are the first agents to directly target HDL and dramatically raise good cholesterol levels. However, the prototype raised blood pressure and increased cardiovascular events, including death, in the 2007 ILLUMINATE trial and never came to market.

But hopes for a safe and effective sibling never dimmed. Nicholls and colleagues edified the believers with preliminary data on evacetrapib. The trial randomized 393 patients to evacetrapib or placebo, either alone or in combination with a statin (e.g. rosuvastatin). Three doses of evacetrapib were analyzed (30 mg, 100 mg, and 500 mg). The investigators found highly significant and impressive increases in HDL, particularly when paired with statins, and incremental LDL lowering. There was no significant effect on blood pressure.

The trial wasn’t designed to assess clinical outcomes, but evacetrapib’s effects on surrogate markers bode well for its further development.


Patients with severely weakened hearts are at risk for sudden death due to ventricular arrhythmias (dangerous fast rhythms that come from the ventricles or pumping chambers of the heart). The only intervention proven to prevent sudden death is a special pacemaker called an implantable cardioverter-defibrillator (ICD), which senses these dangerous rhythms and can shock the heart back into normal rhythm. However, major trials have shown that ICDs should not be implanted immediately in patients. And based on these trials, guidelines mandate that they not be implanted for at least 40 days after a heart attack and 3 months after PCI or bypass surgery. The risk of sudden death is relatively high during these waiting periods.

To address this dilemma, the wearable defibrillator–known as LifeVest (–was developed for use while patients await ICD implant. The LifeVest is effective in terminating ventricular arrhythmias via an electric shock delivered through adhesive pads applied to the chest. Intuitively and anecdotally, this saved lives, but evidence of a mortality benefit was lacking.

Until now. In an intriguing abstract, Zishiri and colleagues from Cleveland Clinic examined the outcomes of 800 patients with weak hearts given LifeVests before hospital discharge after PCI or bypass versus a cohort discharged without. They found a 57% lower death rate among the PCI patients and a 38% lower death rate among bypass patients given a wearable defibrillator. This was a retrospective study and not a randomized trial (which is in the works), but it provides initial evidence that our gut feeling about the LifeVest was probably right.


An unfortunate characteristic of heart muscle is that once it dies, it cannot regenerate. Thus, heart attack survivors are left with scarring and weakened hearts. Despite improvements in medications and revascaularization (PCI and bypass) heart failure is still the most common discharge diagnosis among those 65 and over. But what if we could help the heart structurally heal itself?

The SCIPIO investigators infused stem cells harvested from patients’ right atria into their hearts after bypass surgery. Over a 4 month period, they saw a significant improvement in pumping function, which at 1 year had reached 12%. They also found that the amount of scar in the patients’ hearts had significantly decreased. We know that risk of death is proportional to how weak the heart is. This tiny trial of 14 patients provides a tantalizing glimpse of a new age in heart failure treatment.


Yeah, the TIMI crew is back—this dovetailed nicely, didn’t it? As mentioned earlier, antiplatelet drugs are the backbone of heart attack management both initially and long term. Clopidogrel in particular has become one of the most prescribed medications, with sales in excess of $6 billion in 2010. There is a bit of a molecular monkey wrench, though: a certain proportion of patients are “insensitive” to clopidogrel because of a genetic variation (known as CYP2C19*2) in a protein that affects its metabolism. Because clopidogrel does not work as well in these patients, they have an increased risk of recurrent heart attacks.

The ELEVATE investigators examined subjects with stable coronary disease and CYP2C19*2. They increased the dose of clopidogrel while analyzing how their platelets responded. Doses ranging from the standard 75 mg to 300 mg daily were administered, and platelet function testing was performed after 2 weeks. Higher doses resulted in reduced platelet function in patients with one copy of the gene but not with two. There was no excess bleeding. So we can sort of beat the gene with more clopidogrel. But the GRAVITAS trial showed that higher doses of clopidogel did not affect clinical outcomes in patients with resistant platelets. And newer, more potent members of the clopidogrel drug class are quickly making the whole argument moot.



Zishiri ET, Cronin E, Williams S, et al. Abstract 9816: Use of the Wearable Cardioverter Defibrillator and Survival After Coronary Artery Revascularization in Patients with Left Ventricular Dysfunction. Circulation 2011; Suppl

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