Dual Antiplatelet Therapy Versus Aspirin in Patients With Stroke or Transient Ischemic Attack

Meta-Analysis of Randomized Controlled Trials

Kirtipal Bhatia, MD; Vardhmaan Jain, MD; Devika Aggarwal, MD; Muthiah Vaduganathan, MD, MPH; Sameer Arora, MD, MPH; Zeeshan Hussain, MD; Guneesh Uberoi, MD; Alfonso Tafur, MD, MSc; Cen Zhang, MD; Mark Ricciardi, MD; Arman Qamar, MD, MPH


Stroke. 2021;52(6):e217-e223. 

In This Article

Abstract and Introduction


Background and Purpose: Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there is emerging evidence for the role of short-term dual antiplatelet therapy (DAPT) in preventing recurrent stroke.

Methods: We conducted a systematic review and study-level meta-analyses of randomized controlled trials comparing outcomes of early initiation of short-term DAPT (aspirin+P2Y12 inhibitor for up to 3 months) versus aspirin alone in patients with acute stroke or transient ischemic attack. Primary efficacy outcome was risk of recurrent stroke and primary safety outcome was incidence of major bleeding. Secondary outcomes studied were risk of any ischemic stroke, hemorrhagic stroke, major adverse cardiovascular events, and all-cause death. Pooled risk ratios (RRs) and CIs were calculated using a random-effects model.

Results: Four trials with a total of 21 459 patients were included. As compared to aspirin alone, DAPT had a lower risk of recurrent stroke (RR, 0.76 [95% CI, 0.68–0.83]; P<0.001; I2=0%) but a higher risk of major bleeding events (RR, 2.22 [95% CI, 1.14–4.34], P=0.02, I2=46.5%). Patients receiving DAPT had a lower risk of major adverse cardiovascular events (RR, 0.76 [95% CI, 0.69–0.84], P<0.001, I2=0%) and recurrent ischemic events (RR, 0.74 [95% CI, 0.67–0.82], P<0.001, I2=0%).

Conclusions: As compared to aspirin alone, short-term DAPT within 24 hours of high-risk transient ischemic attack or mild-moderate ischemic stroke reduces the risk of recurrent stroke at the expense of higher risk of major bleeding.

Graphic Abstract: An online graphic abstract is available for this article.


Patients who experience a transient ischemic attack (TIA) or minor ischemic stroke face a high risk of recurrent thrombotic events, especially within 3 months of the index event.[1–3] The efficacy and safety of aspirin in preventing the incidence and lessening the severity of recurrent stroke is well established.[2,4,5] Platelet inhibition with dipyridamole alone or with aspirin is not superior to aspirin alone,[5] and triple antiplatelet therapy with aspirin, clopidogrel, and dipyridamole increases the risk of major bleeding.[6] Although dual antiplatelet therapy (DAPT) with combination of aspirin with a P2Y12 inhibitor has become the cornerstone of antithrombotic therapy in patients with acute coronary syndromes, the role of this approach in patients presenting with ischemic stroke or TIA is not definitively established. The recently published THALES study (Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) is the largest randomized controlled trial comparing aspirin with DAPT in patients with minor stroke. This trial compared aspirin monotherapy to aspirin plus ticagrelor, rather than clopidogrel. This has renewed the interest in optimizing antithrombotic therapy after ischemic stroke or TIA. In this meta-analysis, we compare the safety and efficacy of aspirin plus a P2Y12 inhibitor with aspirin alone for the prevention of recurrent stroke in patients with minor ischemic stroke or high-risk TIA.