POINT trial: Clopidogrel and Aspirin for Acute Ischemic Stroke [Classics Series]

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials

1. In this randomized, controlled trial, combination therapy with aspirin and clopidogrel resulted in a lower risk of major ischemic events at 90 days versus aspirin alone for patients with acute ischemic stroke or high-risk transient ischemic attack.

2. Combination therapy with aspirin and clopidogrel resulted in a higher risk of major hemorrhage event at 90 days than aspirin alone.

Original Date of Publication: July 2018

Study Rundown: The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial evaluated the use of dual antiplatelet therapy (clopidogrel with aspirin) versus aspirin alone to reduce the risk of recurrent stroke in patients with acute ischemic stroke or high-risk transient ischemic attack (TIA). Although the trial showed improved efficacy for dual antiplatelet therapy versus aspirin alone (p = 0.02), it was ultimately halted before completion due to a clear risk of increased major hemorrhage for participants in the treatment arm. Notably, although risk of recurrent ischemic stroke was reduced for the dual antiplatelet group, there was no significant difference in efficacy for reducing myocardial infarction events (p = 0.46) or death from ischemic vascular causes (p = 0.52). Based on these results, the authors estimate that, per 1000 patients treated with dual antiplatelet therapy, 15 ischemic events would be prevented, and 5 major hemorrhages would be precipitated by 90 days. The main strength of this study was its relatively large sample size and strong trial design, taking place at numerous centers internationally. Limitations, however, include the exclusion of certain patient groups, such as those with moderate, severe

Click to read the study in NEJM

In-Depth [randomized controlled trial]:The POINT trial randomized a total of 4881 patients at 269 centers across the world between May 2010 and December 2017. Eligible patients had had either an acute ischemic stroke scored as less than 3 on the National Institutes of Health Stroke Scale (NIHSS) or a TIA with a score of greater than 4 on the ABCD2 scale within 12 hours. Those in the clopidogrel group received a 600 mg loading dose on day 1 followed by 75 mg per day. Aspirin dose ranged from 50-325 mg per day in both groups. Overall, those receiving aspirin with clopidogrel had a significantly improved primary efficacy outcome (a composite of ischemic stroke, myocardial infarction or death from ischemic vascular event) versus aspirin alone (p = 0.02). However, these significant differences did not persist in secondary efficacy outcomes for myocardial infarction or death from ischemic event in isolation. Major hemorrhage, the primary safety outcome, occurred in 0.9% of the dual antiplatelet group and 0.4% of the aspirin group (p = 0.02). This exceeded the prespecified boundary for safety signal, thus resulting in trial discontinuation in August 2017.

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. New England Journal of Medicine. 2018 Jul 19;379(3):215–25.

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