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Are 3 Antiplatelet Agents Better Than 1 or 2 for Recurrent Stroke Prevention?

Information sourced from NEJM Journal Watch:

Are Three Antiplatelet Agents Better Than One or Two for Recurrent Stroke Prevention?

Not in patients with a recent stroke or TIA, new findings demonstrate.

For the approximately 80% of patients with ischemic stroke or transient ischemic attack (TIA) without cardiac embolism antiplatelet therapy is recommended for future stroke prevention. Guidelines recommend aspirin monotherapy, clopidogrel monotherapy, or aspirin plus extended release dipyridamole (DP). To determine whether three antiplatelet agents used simultaneously provides greater protection than standard treatment, researchers randomized 3096 patients (mean age, 69; 63% men) from four countries over a 7-year period to “triple therapy” (usually 75 mg aspirin, 75 mg clopidogrel, and 400 mg DP daily) or standard therapy (clopidogrel monotherapy or aspirin plus DP). Patients qualified with an ischemic stroke (72% of the cohort) or TIA in the preceding 48 hours, and treatments were continued for 30 days. The primary endpoint was stroke or TIA during a 90-day follow-up period, assessed by central telephone calls.

The trial was stopped for futility. The two groups did not differ significantly in the primary outcome (stroke/TIA rate, 6% triple therapy, 7% standard therapy). Triple-therapy patients had a 2.5 times higher risk for bleeding, including a higher rate of fatal/major bleeds (3% with triple therapy, 1% with standard therapy).


Antithrombotic therapy use is predicated on prevention of ischemic events outweighing any increase in bleeding. These findings show that there are limits to combining multiple antithrombotic agents. In patients with a recent stroke or TIA, triple therapy had no demonstrable benefit for stroke prevention, and significant bleeding events occurred at an excess rate with triple therapy. Sometimes “less is more,” or at least better for the patient.

Seemant Chaturvedi, MD reviewing Bath PM et al. Lancet 2017 Dec 20.


Bath PM et al. Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): A randomised, open-label, phase 3 superiority trial. Lancet 2017 Dec 20; [e-pub].

NEJM Journal Watch is produced by NEJM Group, a division of the Massachusetts Medical Society. Copyright ©2018 Massachusetts Medical Society. All rights reserved.

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