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Is Aspirin Plus Clopidogrel Safe and Effective After Stroke?

Combination therapy was not superior to clopidogrel alone in a secondary prevention trial.

Aspirin and clopidogrel (Plavix) are used -- sometimes individually, sometimes together -- as secondary preventive measures after strokes. Combined therapy (75-mg clopidogrel plus 75-mg aspirin daily) was compared with clopidogrel alone in this randomized, double-blind, international trial, funded by the maker of clopidogrel. The trial included 7599 patients who had suffered ischemic strokes or transient ischemic attacks (TIAs) during the previous 3 months. All patients had at least one of five other risk factors: previous stroke, previous myocardial infarction, angina, diabetes, or symptomatic peripheral arterial disease.

The primary composite endpoint was ischemic stroke, MI, vascular death, and hospitalization for TIA, angina, or peripheral arterial disease. During 18 months of follow-up, this endpoint occurred in 15.7% of combined-therapy recipients and in 16.7% of clopidogrel-alone recipients -- a nonsignificant difference. Life-threatening bleeding complications were significantly more common with combined therapy (2.6% vs. 1.3%). All-cause mortality rate was identical in the two groups.

Comment: In this study of secondary prevention in high-risk stroke patients, the combination of clopidogrel plus aspirin was not superior to clopidogrel alone but was associated with increased risk for serious bleeding. An editorialist notes that patients who already are taking combined therapy after stroke should be advised of this risk. In my view, it would have been more appropriate to compare aspirin alone and combined therapy, because clopidogrel was not convincingly better than aspirin among stroke patients in the frequently cited CAPRIE study (Lancet 1996; 348:1329).

— Allan S. Brett, MD

Published in Journal Watch General Medicine August 10, 2004

Citation(s):

Diener H-C et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): Randomised, double-blind, placebo-controlled trial. Lancet 2004 Jul 24; 364:331-7.

• Medline abstract (Free)

Rothwell PM. Lessons from MATCH for future randomised trials in secondary prevention of stroke. Lancet 2004 Jul 24; 364:305-7.

• Medline abstract (Free)