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Medication News & Update

Clopidogrel plus aspirin not beneficial (and possibly harmful) in a broad population with cardiovascular disease or with high risk of cardiovascular disease

 This posting was at Clot Care Web site

Tera D. Moore, Pharm.D., BCPS*
April, 2006

The CHARISMA investigators1 conducted a prospective, multicenter, randomized, double-blind, placebo controlled study to evaluate the efficacy and safety of clopidogrel (75 mg per day) plus aspirin (75 to 162 mg per day) compared with aspirin alone. The broad population included 15,603 patients with either clinically evident cardiovascular disease ("symptomatic") or multiple risk factors ("asymptomatic"). However, it should be noted that up to about 40% of "asymptomatic" may have had prior cardiovascular events; but not within the time frame to qualify them as "symptomatic" by the study criteria. With a median of 28 months follow-up, the primary efficacy end point, a composite of myocardial infarction (MI), stroke, or death from cardiovascular causes occurred in 6.8% in the clopidogrel group and 7.3% in the placebo group (RR 0.93; 95% CI 0.83-1.05; p = 0.22). The rate of severe bleeding was 1.7% in the aspirin and clopidogrel group and 1.3% in the aspirin and placebo group (p = 0.09). Corresponding moderate bleeding rates were 2.1% in the clopidogrel and aspirin group, compared with 1.3% in the aspirin and placebo group (p<0.001). Because the benefits of therapy were assessed by a composite endpoint, it seems fair to assess the safety with a combined endpoint of severe and major bleeding rates (either required transfusion). The combined severe and major bleeding rates was 3.8% in the clopidogrel plus aspirin group and 2.6% in the aspirin and placebo group; for an absolute difference of 1.2%. The primary efficacy end point in the subgroup of "asymptomatic" or primary prevention cohort was 6.6% with clopidogrel and 5.5% in placebo group (p=0.20), more specifically the rate of death from cardiovascular causes was 3.9% for those receiving clopidorel and 2.2% in the placebo group (p=0.01). The American Heart Association issued a statement on the uses of clopidogrel, they include: some patients who have had an MI, patients who have had angioplasty for unstable angina or heart attack, patients who have received either a bare-metal or drug-eluting stent, patients with peripheral artery disease, patients who have had a transient ischemic attack or other stroke.2

Lastly, the issue of sub-group analysis with this study was addressed in an accompanying editorial by Drs. Pfeiffer and Jarcho.3

References:

1. Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006; DOI:10.1056/NEJMoa060989. Available at: http://www.nejm.org.
   
   
2. American Heart Association. Updated American Heart Association Statement: Patient guidance based on results of the CHARISMA trial. March 16, 2006. http://www.americanheart.org/presenter.jhtml?identifier=3038359.
   
   
3. Pfeffer MA and Jarcho JA. The charisma of subgroups an dthe subgroups of CHARISMA. N Engl J Med. 2006; DOI:10:1056/NEJMe068057. Available at: http://www.nejm.org.

*Dr. Moore is a guest editor for ClotCare. Dr. Moore is a primary care clinical specialist with the South Texas Veterans Health Care System in San Antonio, TX.

http://www.clotcare.com/clotcare/clopidogrelplusaspirincardiovascular.aspx