How effective is dual antiplatelet therapy for secondary prevention of ischemic stroke?

Updated: May 27, 2020
  • Author: Edward C Jauch, MD, MS, FAHA, FACEP; Chief Editor: Helmi L Lutsep, MD  more...
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A systematic review and meta-analysis of 12 randomized trials involving 3766 patients concluded that, compared with aspirin alone, dual antiplatelet therapy with aspirin plus either dipyridamole or clopidogrel appears to be safe and effective in reducing stroke recurrence and other vascular events (ie, transient ischemic attack [TIA], acute coronary syndrome, MI), in patients with acute ischemic stroke or TIA. [133] Dual therapy was also associated with a nonsignificant trend toward increased major bleeding.

The European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) showed that the combination of aspirin and dipyridamole was preferable to aspirin alone as antithrombotic therapy for cerebral ischemia of arterial origin. [134] In ESPRIT, secondary prevention was started within 6 months of a TIA or minor stroke of presumed arterial origin.

The addition of extended-release dipyridamole to aspirin therapy appears to be equally safe and effective whether started early or late after stroke. A German study in 543 patients found no significant difference in disability at 90 days, regardless of whether dipyridamole was started within 24 hours of stroke or TIA onset or after 7 days of aspirin monotherapy. [135]

In contrast, the Management of AtheroThrombosis with Clopidogrel in High-risk patients with recent transient ischaemic attack or ischaemic stroke (MATCH) trial, which included 7599 patients, found that adding aspirin to clopidogrel did not significantly reduce major vascular events. However, the risk of life-threatening or major bleeding was increased by the addition of aspirin. [136]

Research shows that aspirin combined with rivaroxaban cuts the ischemic stroke rate by almost half without significantly increasing the risk for intracerebral hemorrhage (ICH) compared with aspirin alone. The COMPASS trial studied 27,395 patients with stable atherosclerotic vascular disease divided into three treatment groups: aspirin 100 mg a day, rivaroxaban 5 mg twice daily, and a combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg per day. The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction and occurred in 379 patients in the combination group compared to 496 patients taking aspirin alone. However, bleeding events occurred in more patients in the combination group (3.1% vs 1.9%; HR, 1.70; 95% CI, 1.40 - 2.05; P< .001). [51]

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