BACKGROUND: In patients with acute minor ischemic stroke or high-risk transient ischemic attack enrolled in the POINT trial, the combination of clopidogrel and aspirin for 90 days reduced major ischemic events but increased major hemorrhage compared to aspirin alone.METHODS: In a secondary analysis of POINT (N=4,881), we assessed the time course for benefit and risk from the combination of clopidogrel and aspirin. The primary efficacy outcome was a composite of ischemic stroke, myocardial infarction, or ischemic vascular death. The primary safety outcome was major hemorrhage. Risks and benefits were estimated for delayed times of treatment initiation using left-truncated models.RESULTS: Through 90 days, the rate of major ischemic events was initially high then decreased markedly, while the rate of major hemorrhage remained low but relatively constant throughout. Using a model-based approach, the optimal change-point for major ischemic events was 21 days (0-21 days HR 0.65 for clopidogrel-aspirin vs. aspirin, 95% CI 0.50-0.85, p=0.0015, compared to 22-90 days HR 1.38, 95% CI 0.81-2.35, p=0.24). Models showed benefits of clopidogrel-aspirin for treatment delayed as long as 3 days after symptom onset.CONCLUSIONS: The benefit of clopidogrel-aspirin occurs predominantly within the first 21 days, and outweighs the low, but ongoing risk of major hemorrhage. When considered with the results of CHANCE, a similar trial treating with clopidogrel-aspirin for 21 days and showing no increase in major hemorrhage, these results suggest limiting clopidogrel-aspirin use to 21 days may maximize benefit and reduce risk after high-risk TIA or minor ischemic stroke.CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique Identifier: NCT00991029.
View details for DOI 10.1161/CIRCULATIONAHA.119.040713
View details for PubMedID 31238700