Certain Subgroups May Benefit From Dual Therapy, Others Should Avoid It
March 14 , 2006
A Cleveland Clinic-led international study has found that long-term therapy with low-dose aspirin plus another antiplatelet agent, clopidogrel (Plavix®), is not more effective than aspirin alone in preventing heart attack, stroke, and cardiovascular death in a broad patient population.
Results from the study will be presented at the 55th Annual Scientific Session of the American College of Cardiology (ACC) in Atlanta on March 12 and simultaneously published online in the New England Journal of Medicine.
The majority of patients in the study, those who had already experienced a heart attack or stroke or who had symptomatic blockages in their legs (Peripheral Arterial Disease or PAD), did benefit from the dual therapy, demonstrating a significant 12.5% reduction in their risk of heart attack and stroke. Unexpectedly, researchers also found that the subgroup of patients with multiple risk factors for heart attack or stroke but who did not have established cardiovascular disease may have experienced some harm, including higher rates of severe bleeding.
“There are several important findings from this study,” says Deepak L. Bhatt, M.D., lead author and director of the Cardiovascular Trials Unit and associate director of the Cleveland Clinic Cardiovascular Coordinating Center. “Although the study found that clopidogrel plus aspirin was not effective in patients with multiple risk factors only, it may be effective in secondary prevention, or preventing a second heart attack or stroke in people who have already experienced one of these events or who have PAD. This is a large population that is in need of improved therapies.”
CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) was a prospective, multicenter, randomized, double-blind, placebo controlled study of the safety and efficacy of clopidogrel plus aspirin compared to aspirin alone in stable patients at high risk for a cardiovascular event. Prior studies had established the efficacy of clopidogrel plus aspirin in patients with acute coronary syndromes, but long term dual therapy had not been evaluated in a broad population of stable patients.
The CHARISMA study included 15,603 patients with either diagnosed cardiovascular disease (~80% of the study population) or multiple risk factors for cardiovascular disease (~20% of study population). Patients were randomly assigned to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin for a median of 28 months. The primary endpoint was measured as a combination of heart attack, stroke, or death from cardiovascular causes.
Dr. Bhatt says further investigation is needed to better understand how dual antiplatelet therapy may be optimally utilized in appropriate populations. “Our findings from the CHARISMA trial suggest a significant benefit of dual antiplatelet therapy in patients with established cardiovascular disease, while demonstrating a lack of benefit and increased bleeding in patients only having multiple risk factors. Future research will help determine exactly which patients need more aggressive antiplatelet therapy than just an aspirin a day to prevent heart attacks and strokes.”
Funding for the CHARISMA trial was provided by Sanofi-Aventis and Bristol-Myers Squibb. Dr. Bhatt has been paid honoraria from both companies in the past, though he currently donates such honoraria to a not-for-profit organization.
Miller Family Heart & Vascular Institute is the recognized world leader in diagnosis and treatment of cardiovascular disease. Cleveland Clinic has been ranked No. 1 in the nation for cardiac care by U.S. News & World Report every year since 1995. Cleveland Clinic has been ranked among America’s Ten Best Hospitals every year since 1990 by U.S. News & World Report.
The Cleveland Clinic Foundation, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. The Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names The Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Approximately 1,500 full-time salaried physicians at The Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2004, patients came for treatment from every state and 100 countries. The Cleveland Clinic website address is www.clevelandclinic.org.
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