Time Course for Benefit and Risk of Clopidogrel and Aspirin after Acute Transient Ischemic Attack and Minor Ischemic Stroke: A Secondary Analysis from the POINT Randomized Trial. Circulation Johnston, S. C., Elm, J. J., Easton, J. D., Farrant, M., Barsan, W. G., Kim, A. S., Lindblad, A. S., Palesch, Y. Y., Zurita, K. G., Albers, G. W., Cucchiara, B. L., Kleindorfer, D. O., Lutsep, H. L., Pearson, C., Sethi, P., Vora, N., POINT and Neurological Emergencies Treatment Trials Network Investigators 2019


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