Clinical question: Does loading clopidogrel with aspirin reduce recurrent stroke after moderate to high-risk transient ischemic attack (TIA) or minor stroke if started within 24 hours of primary event?
Background: Recurrent stroke risk is highest during the first few weeks after TIA or minor stroke.
Study design: Randomized, double-blinded, placebo-controlled trial.
Setting: Multi-center health system in China.
Synopsis: More than 5100 patients were randomized within 24 hours after minor ischemic stroke (NIHSS<=3) or high-risk TIA (ABCD2>= 4) to loading dose clopidogrel 300 mg, then 75 mg po daily x 90 days in addition to aspirin 75 mg daily for the first 21 days or aspirin 75 mg po daily x 90 days + placebo. Within 90 days, recurrent stroke was higher in aspirin + placebo group compared to aspirin + clopidogrel (11.7% event rate compared with 8.2%). Moderate to severe bleeding risk was the same (0.3%) in both groups.
Strict eligibility criteria in this study might limit generalizability to the general public. This study occurred in China, where the recurrent stroke rate was higher (near 10%) than the rate seen in primary stroke centers in more developed countries (3% to 5%), perhaps because of less emphasis on secondary risk prevention (including hypertension and hyperlipidemia) in China.
Also, the distribution of stroke subtype in China (more intracranial atherosclerosis than in other populations) might have affected the study outcomes. Because of these limitations, more research needs to be done to confirm these findings for other populations.
Bottom line: Adding clopidogrel to aspirin reduced recurrent cerebrovascular event after high-risk TIA or minor ischemic stroke in China, but generalizability to other patient populations is not clear.
Citation: Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. New Engl J Med. 2013;369:11-19.