Restrict clopidogrel and aspirin to 21 days in high risk TIA patients, recommends new study

Benefits restricting clopidogrel and aspirin to 21 days outweighed the risk of hemorrhage associated with it in mild stroke or high-risk TIA patients, according to a study published in the journal Circulation. The study was a secondary-analysis of Platelet-Oriented Inhibition in New TIA and minor stroke (POINT) trial which suggested that clopidogrel-aspirin reduced major ischemic events but was associated with a small increase in major hemorrhage compared to aspirin alone.

In secondary analysis of patients with minor ischemic stroke or high-risk transient ischemic attack in the POINT randomized trial, reduction in major ischemic events with clopidogrel combined with aspirin compared to aspirin alone was greatest with 21 days of treatment rather than the full 90-day treatment in the trial, and risk of major hemorrhage was less during this period. Models suggested that treatment initiated as late as 3 days after symptom onset may still be beneficial.

In this secondary analysis of POINT, a team of scientists from the University 0f California 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.

Key findings

• 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.


• Models showed benefits of clopidogrel-aspirin for treatment delayed as long as 3 days after symptom onset.

"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." the authors wrote.