Combination Therapy More Effective than Aspirin Alone For Stroke Prevention According to INSPIRES Clinical Trial

Combination therapy, consisting of clopidogrel with aspirin, initiated within 72 hours of stroke onset in people with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause, was associated with a lower risk of new stroke at 90 days compared to the use of aspirin alone, according to results from the INSPIRES clinical trial (NCT03635749). Previous studies have shown dual antiplatelet therapy to be effective at stroke prevention when administered within up to 24 hours following stroke. Combination therapy also was associated with a slightly higher risk of bleeding than aspirin monotherapy as reported in The New England Journal of Medicine.

The randomized, placebo-controlled, 2-by-2 factorial trial was conducted across 222 hospitals in China, enrolling a total of 6100 participants with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not received thrombolysis or thrombectomy. Within 72 hours of symptom onset, participants were randomized 1:1 to receive either clopidogrel in combination with aspirin or a placebo in combination with aspirin. New stroke and moderate-to-severe bleeding were assessed as primary efficacy and safety outcomes, respectively.

Assignment to a treatment group occurred no longer than 24 hours after stroke onset in 12.8% of participants and between 24 and 72 hours in 87.2% of participants. New stroke occurred in 7.3% (n=222) of participants who received clopidogrel in combination with aspirin, and in 9.2% (n=279) of participants who received placebo and aspirin (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.94; P=0.008). Moderate-to-severe bleeding occurred in 0.9% (n=27) of participants who received clopidogrel and aspirin and 0.4% (n=13) of participants who received placebo and aspirin.