American Heart Association Scientific Sessions 2011

American Heart Association Scientific Sessions 2011Orlando, Florida

More than 22,000 people attended the 2011 American Heart Association (AHA) Scientific Sessions in Orlando, Florida, November 12 to 16, 2011. The sessions provided 5 days of comprehensive education through more than 4000 presentations given by some of the world’s top experts in cardiovascular disease.

This Meeting Report covers 5 studies presented at the AHA meeting: ATLAS ACS 2-TIMI 51, MI FREEE, ELEVATE-TIMI-56, AIM-HIGH, and TRA-CER.

Rivaroxaban Reduces Risk of Death, Heart Attack, Stroke in ACS Treatment

Adding rivaroxaban (Xarelto) to standard treatment of acute coronary syndrome (ACS) lowered risk of death, heart attack, and stroke in ACS patients, according to results of the Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 Trial (ATLAS ACS 2-TIMI 51). However, patients taking rivaroxaban were more likely to experience major bleeding than patients taking placebo.

C. Michael Gibson, MD, of Harvard Medical School, senior investigator of the TIMI Study Group and principal investigator in the ATLAS ACS studies of rivaroxaban, noted that patients face a 10% or higher risk of repeat heart attack, stroke, or death 1 year after an ACS event. ATLAS ACS 2-TIMI 51 examined whether reducing thrombin production with rivaroxaban reduced the risk of death, stroke, or heart attack in 15,526 patients hospitalized with a recent heart attack or unstable angina.

All patients were treated with low-dose aspirin, and at the physician’s discretion were further stratified by the concomitant administration of a thienopyridine (clopidogrel or ticlopidine—stratum 2) or not (stratum 1). Patients were randomly assigned in a 1:1:1 ratio within each stratum to either rivaroxaban 2.5 mg twice daily, rivaroxaban 5.0 mg twice daily, or placebo twice daily. After 1 year:

• Patients who took rivaroxaban had a 16% reduced risk of cardiovascular death, stroke, or heart attack compared with those who did not.

• The risk of death (including all causes) was reduced by over 30% in patients taking rivaroxaban.

• Stent thrombosis was reduced by 31% in patients who took rivaroxaban compared with those who did not.

• Although there were more bleeding incidents in the rivaroxaban group and the rate of intracranial bleeding was higher than among the placebo group, there was no increase in fatal bleeding.

Dr Gibson concluded, “If the data from ATLAS ACS 2-TIMI 51 were extrapolated into clinical practice, we could potentially see 1 life saved for every 56 patients, treated with this combination of therapies over a 2-year period.”

This trial was funded by Johnson & Johnson. This study was published in The New England Journal of Medicine.

Free Heart Meds Reduce Heart Attacks, Heart Failure But Not Revascularization Rates

Heart attack patients whose health insurance company paid the entire amount for their heart medications had lower rates of rehospitalization for heart attacks and heart failure than patients who had prescription co-pays, according to the Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MI FREEE) trial. However, there was no reduction in the rate of revascularization.

The study was funded by Aetna Inc. The company’s costs did not increase even though it spent more on prescriptions, because there was less spent to treat subsequent health problems.

MI-FREEE also found that patients who got the free heart medications were more likely to take them as prescribed. Lead author Niteesh K. Choudhry, MD, PhD, of Harvard University and Brigham & Women’s Hospital in Boston, said that only half of patients adhere to long-term therapy. Cost appears to be one reason for nonadherence, he noted, even among patients with health insurance.

In the study of 5855 heart attack patients, 2845 did not pay anything for their statins, β-blockers, angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers prescribed post—heart attack.

These patients were 4% to 6% more likely to take the medications than the 3010 patients who had co-pays.

MI-FREEE found that 17.6% of those with free medications had a major cardiac event or underwent revascularization, compared with 18.8% of those with co-pays—a difference that was not statistically significant, but when assessed separately from revascularization, there was a significant reduction in the rate of major cardiac events. After approximately 1 year, the rate of heart attacks, angina, and heart failure dropped 14% among patients getting free heart medications.

Patients saved 26% on their overall out-of-pocket health care costs and paid fewer co-pays because their health had improved.

Aetna Inc found “compelling” improvements in the results, and said that the company will begin offering a benefits plan in 2013 that will enable heart attack survivors to get certain medications at no or reduced out-of-pocket costs (Wall Street Journal, November 15, 2011). Based on the study’s findings, Dr Choudhry recommended that insurance companies consider paying for the total cost of heart medications after a heart attack. This study was funded by Aetna Inc, which also provided the medications for the study, and the Commonwealth Fund.

This study was published in The New England Journal of Medicine.

Adding Niacin Won’t Lower Risk of Heart Attack, Stroke if LDL Is Controlled

Adding high doses of niacin doesn’t lower the risk of heart attack or stroke in patients with stable coronary heart disease whose low-density lipoprotein (LDL) cholesterol is controlled with medication, according to the AIM-HIGH study (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health). Although taking niacin raised levels of high-density lipoprotein (HDL) cholesterol and lowered triglycerides, those changes did not translate into reduced numbers of heart attacks and strokes.

AIM-HIGH randomized 3414 patients 45 years or older with stable, non-acute CVD and low HDL cholesterol to extendedrelease niacin (ERN) or placebo. A total of 1718 patients got high-dose (1500 to 2000 mg/d) ERN in addition to LDL cholesterol reduction, while 1696 patients received placebo.

After 2 years, HDL and triglyceride levels continued to be improved in the niacin group, with a 25% increase in HDL and a 29% drop in triglycerides. In the placebo group there was a modest change of a 10% increase in HDL and an 8% drop in triglyceride levels.

Although the niacin group had a decrease in LDL of approximately 12%, it didn’t translate into fewer heart attacks, strokes, or heart-related deaths or hospitalizations, which occurred in 16.4% of patients taking niacin and 16.2% of those on placebo— a difference that is not statistically significant (P = 0.80).

Because of the findings, the trial was halted 18 months before its planned completion. Lead researcher William E. Boden, MD, of the University of Buffalo in New York, said, “If you are a patient with stable cardiovascular disease who has achieved and maintained very low levels of LDL cholesterol on a statin, these findings indicate that the addition of high-dose niacin does not improve your risk for future events and is therefore not needed.” He noted that the AIM-HIGH results apply only to the 20% of heart disease patients who achieve very low LDL, and said it isn’t known whether raising HDL would be beneficial to the 80% of patients who are unable to lower their LDL as much. AIM-HIGH also did not address the possible benefit of niacin therapy in patients who have had a recent heart attack or heart-attack related chest pain, researchers noted.

Controversy arose at the AIM-HIGH press conference when discussant Philip Barter, MD, of the University of Sydney, called the trial “appalling” and underpowered to test the potential benefits of niacin (Forbes, November 15, 2011). “Whatever conclusions are drawn from this trial, it cannot be emphasized too much that it has not tested the HDL hypothesis,” he said. “I do not believe we should change practice.” Dr Barter said any change should await results of the much larger HPS2- THRIVE study in a few years, which is sufficiently powered to answer the question.

American Heart Association spokesperson Roger Blumenthal said that while there is currently no evidence to support the use of niacin, it is reasonable to give it to patients whose high LDL levels persist after maximal statin therapy. However, for people with LDL levels in the 70s, it is hard to justify.

AIM-HIGH was primarily funded by the NHLBI. Abbott Laboratories gave a supplemental unrestricted grant to the NHLBI and provided ERN. Merck provided the simvastatin used in the trial.

This study was published in The New England Journal of Medicine.

Triple-Dose Clopidogrel Can Work in Patients With Genetic Resistance

Higher doses of clopidogrel (Plavix) were more effective than standard dosing in patients with a gene mutation found in up to one-third of patients that blocks some of clopidogrel’s effect. The ELEVATE-TIMI-56 trial is the first to systematically examine high-maintenance doses of clopidogrel up to 300 mg/d (4 times the usual dose) in patients with a genetic variation that blocks the CYP2C19 gene and has been linked to unresponsiveness to clopidogrel. Patients with the mutation may not get the expected effect of clopidogrel on inhibiting platelets and are still at high risk for heart attack despite taking the medication.

In the ELEVATE-TIMI-56 trial, patients were genotyped as carriers or non-carriers of the allele. Non-carriers were randomized to receive either 75 mg or 150 mg. Carriers were randomized to receive either a 75-mg, 150- mg, 225-mg, or 300-mg dose. The study included 335 patients from 32 US sites; patients were observed over 8 weeks of treatment.

Researchers found that increasing drug levels improved the antiplatelet effect in patients with 1 copy of the gene variation. When doses were tripled and quadrupled, only 10% of patients did not have the optimal response when platelet function was assessed. However, the usual dose of clopidogrel failed to have the desired anti-platelet effect in about half the patients who had a mutation in the gene.

• 52% of patients with 1 copy of the CYP2C19 gene variation didn’t respond optimally at the standard 75 mg/d dose of clopidogrel.

• 26% didn’t respond at 150 mg/d.

• 10% didn’t respond at 225 mg/d and 300 mg/d.

Researchers did not find significant increases in side effects as dosage increased during the duration of the study.

Senior author Marc S. Sabatine, MD, MPH, of Brigham & Women’s Hospital in Boston, said the data provide a rational framework for how to begin approaching alternative dosing of clopidogrel in the one-third of patients who harbor a genetic roadblock to metabolizing clopidogrel appropriately.

This study was funded by an investigator-initiated grant from Bristol-Myers Squibb and sanofi-aventis. This study was published in The Journal of the American Medical Association.

Investigational Antiplatelet Drug Fails To Meet Primary End Point

Researchers with the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA-CER) study reported that vorapaxar, an investigational antiplatelet drug, failed to reduce patients’ risk of experiencing adverse outcomes after treatment for unstable angina or a heart attack due to a partial artery blockage. Vorapaxar is the first in a new class of antiplatelet drugs known as PAR-1 antagonists. Patients taking vorapaxar also had an increased risk of bleeding.

TRA-CER compared vorapaxar with placebo in patients with non-ST-segment elevation acute coronary syndrome. Of 12,944 patients at 818 sites in 37 countries, all received the usual medical care, typically aspirin and clopidogrel as well as catheterization, coronary stenting, or surgery. Half the study participants were given a 40-mg initial dose of vorapaxar, followed by a 2.5-mg daily dose of the drug. The remaining patients received a placebo.

Patients taking vorapaxar were as likely as those given placebo to experience at least 1 of 5 outcomes: cardiovascular-related death, heart attack, stroke, new hospitalization for unstable angina, or urgent revascularization. After 2 years, almost 1 in 5 patients in each group had such an outcome (18.5% for vorapaxar versus 19.9% for placebo).

Patients using vorapaxar had more bleeding and a 3-fold increase in the risk of hemorrhagic stroke. Patients on vorapaxar also had a 14.7% risk of cardiovascular death, heart attack, or stroke, compared with 16% for patients given placebo—not significantly different.

Lead author Kenneth W. Mahaffey, MD, of Duke Clinical Research Institute in Durham, NC, said the findings were surprising in that earlier studies of vorapaxar had not identified an excess bleeding risk. More work is needed to understand this risk and whether it is related to the use of aspirin and clopidogrel in these patients or if there are other factors involved.

The study was funded by Merck Sharp & Dohme Corp.This study was published in The New England Journal of Medicine.