Pamela Cheng, DO

Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, et al. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med. 2018; 379:215-225.

The CHANCE trial had previously shown that dual antiplatelet therapy reduced the risk of recurrent stroke. However, the trial was conducted in a homogenous population in China; therefore, its applicability on an international population was uncertain. Enter the POINT trial.

A total of 4881 patients were enrolled at 269 international sites. Patients had to be at least 18 years of age and randomized within 12 hours after having an acute ischemic stroke with a score of 3 or less on the NIHSS or a high-risk TIA defined as ABCD2 score of 4 or more. Isolated numbness, isolated dizziness, and isolated visual changes were all excluded. Patients were randomly assigned in a 1:1 ratio to receive either clopidogrel plus aspirin or placebo plus aspirin. Patients receiving clopidogrel were given a 600 mg loading dose on day 1, followed by 75 mg daily from day 2 to day 90. Aspirin dose was determined by treating physician but was given in doses ranging from 50 mg to 325 mg daily. The primary outcome was the risk of composite ischemic stroke, myocardial infarction, or death from ischemic vascular causes. The primary safety outcome was the risk of major hemorrhage or death from hemorrhage.

The trial was stopped early due to safety concerns. At the time of trial discontinuation, 4881 patients had been enrolled. The composite primary efficacy outcome occurred in 5% of patients receiving clopidogrel plus aspirin and 6.5% in patients receiving aspirin only [hazard ratio, 0.75 (0.59 to 0.95); p = 0.02]. However, the primary safety outcome occurred in 0.9% of patients receiving clopidogrel plus aspirin and 0.4% in patients receiving aspirin only [hazard ratio, 2.32 (1.10-4.87); p = 0.02]. Thus, the lower rate of ischemic events was balanced by the higher rate of major hemorrhage. Most of the benefit was seen within the first 30 days, and most of the harm was seen between days 8 and 90. Given that the risk of a recurrent ischemic event is especially high within the first week after a TIA or stroke, dual antiplatelet therapy, at least for a limited time, may be beneficial in certain individuals.