By Matthew E. Fink, MD
Feil Professor & Chair of Neurology, Associate Dean for Clinical Affairs, NYP/Weill Cornell Medical College
Dr. Fink reports he is a retained consultant for Procter & Gamble and Pfizer.
Johnston SC, Easton JD, Farrant M, et al; for the Clinical Research Collaboration, Neurological Treatment Trials Network, and the POINT Investigators. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med 2018; May 16. doi:10.1056/NEJMoa1800410. [Epub ahead of print].
After a minor ischemic stroke or transient ischemic attack (TIA), the risk of recurrent ischemic stroke in the next 90 days ranges from 3-15%. Use of aspirin reduces the risk of recurrent stroke by approximately 20%. Clopidogrel inhibits platelet aggregation in a mechanism that is synergistic with aspirin when tested in platelet aggregation assays. The combination of these two drugs has been used effectively to reduce the risk of ischemic events in patients with coronary artery events. These investigators undertook this study to evaluate the effect of clopidogrel plus aspirin, vs. aspirin alone, in an international population of patients who had minor ischemic stroke or TIA — Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT).
From 2010 to 2017, the investigators enrolled 4,881 patients at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand, with most patients (82.8%) enrolled in the United States. After an interim analysis, the investigators halted enrollment after 84% of the anticipated number of patients had been enrolled because the combination of clopidogrel and aspirin was associated with both a lower risk of major ischemic events (ischemic stroke, myocardial infarction, or death from an ischemic vascular event) and a higher risk of major hemorrhage from aspirin alone at 90 days. Five percent of patients receiving clopidogrel plus aspirin and 6.5% of patients receiving aspirin plus placebo (hazard ratio, 0.75; P = 0.02) experienced major ischemic events, with most occurring during the first week after the initial event. Major hemorrhages occurred in 0.9% receiving clopidogrel plus aspirin and 0.4% receiving aspirin plus placebo (hazard ratio, 2.32; P = 0.02). Hemorrhage risk was the same throughout the 90-day follow-up period.
The investigators were unable to compare the disabilities that resulted from ischemic events compared to hemorrhagic events, but mortality was not significantly different between the two groups. Based on this study and the CHANCE trial from China (N Engl J Med 2013;369:11-19), a reasonable approach for treatment would be 30 days of treatment with dual antiplatelet therapy following acute ischemic stroke or TIA, and then
conversion to a single agent. However, such recommendations are my opinion, and not based on evidence from any study.
