Clopidogrel Adds No Benefit to Aspirin in High-Risk Patients
Combo antiplatelet therapy may harm those with diabetes and other CVDrisks
The addition of clopidogrel (Plavix, Sanofi-Aventis/Bristol-Myers Squibb)to a daily low-dose aspirin regimen does not significantly reduce theincidence of death, heart attack, or stroke among people with diabetes orother cardiovascular risk factors, according to research presented at theAmerican College of Cardiology (ACC) Scientific Session, held March11–14 in Atlanta.
While the combination benefits people with a history of cardiovasculardisease (CVD), clopidogrel appears to be linked to more harmful side effectsin people who have only CVD risk factors, say investigators in the Clopidogrelfor High Athero-thrombotic Risk and Ischemia Stabilization, Management, andAvoidance (CHARISMA) study.
“Combination therapy may be useful in a large, new group ofpatients—those with established cardiovascular disease—but offersno benefit whatsoever in patients only having risk factors for developingvascular disease,” says lead investigator Deepak L. Bhatt, MD, directorof cardiovascular clinical trials at the Cleveland Clinic in Ohio.
CHARISMA began with 15,603 patients aged ≥45 years with either multipleCVD risk factors, such as diabetes, hypertension, and dyslipidemia, orestablished CVD, defined as a history of heart attack, stroke, or peripheralvascular disease.
Participants were randomized to receive a daily dose of either low-doseaspirin (75–162 mg) plus clopidogrel (75 mg) or aspirin plus placebo.After an average 28 months of follow-up, the overall rate of death, heartattack, or stroke was 6.8% in the aspirin plus clopidogrel group and 7.3% inthe aspirin plus placebo group—a difference that is not statisticallysignificant. However, the addition of clopidogrel was associated with reducingthe rate of hospitalization for ischemic events (a secondary end point) from17.9% to 16.7%.
When researchers looked at the subgroup of 12,153 people with establishedCVD, 6.9% of those who took aspirin plus clopidogrel had died or suffered aheart attack or stroke during the follow-up period, compared with 7.9% in theaspirin plus placebo group—a risk reduction of about 12%.
Yet the addition of clopidogrel appears to increase the risk ofcardiovascular events for people with risk factors but not establisheddisease. Of the 3,284 patients with multiple cardiovascular risk factors, 6.6%of those who took aspirin plus clopidogrel died or had a heart attack orstroke, compared with 5.5% of those who received aspirin plus placebo.Cardiac-related mortality nearly doubled among those taking clopidogrelcompared with those on aspirin alone—2.2% of those on placebo died,compared with 3.9% of those on clopidogrel.
Results from CHARISMA were published March 12 in the online edition of theNew England Journal ofMedicine1 asthey were being presented at ACC. The paper was scheduled to be published inthe April 20 print edition.
In an accompanying editorial, Marc A. Pfeffer, MD, PhD, of Harvard MedicalSchool, and John A. Jarcho, MD, of Brigham and Women's Hospital, both inBoston, say the CHARISMA trial “argues against the use of dualantiplatelet therapy” in patients with multiple riskfactors.2
Clopidogrel remains indicated to reduce the risk of repeat heart attacks orstrokes in people with a history of those conditions.
The American Heart Association on March 15 issued a statement saying thatthe CHARISMA trial failed to support the use of clopidogrel in patients withstable cardiovascular disease or as a preventive measure in those at high riskfor CVD. However, the association points out that previous trials have shownbenefits of combined therapy for those with unstable coronary syndromes andthose who have had coronary angioplasty with stent placement. Patients alreadytaking clopidogrel should not stop the medication, the statement says.▪
