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


Search Strategy and Study Characteristics

We searched Medline, EMBASE, Web of Science, and Cochrane Central from inception through July 2020 for eligible studies with the terms "ischemia," "stroke," "cerebral infarction," "transient ischemic attack," "aspirin," "clopidogrel," "ticagrelor," "prasugrel," and "antiplatelets." We also searched the references of the included studies to identify any additional studies. We considered trials that included adult patients with acute stroke or TIA randomized to receive antiplatelet therapy within 24 hours of symptom onset and compared safety and efficacy outcomes between DAPT with aspirin and a P2Y12 inhibitor versus aspirin alone. We excluded observational studies for the purpose of this analysis. Two reviewers screened the title and abstracts of the retrieved studies to select studies that met the inclusion criteria. In case of any disagreement, a third reviewer (A.Q.) helped in establishing consensus. The authors declare that all supporting data are available within the article or Data Supplement.

Outcome Measures

Primary efficacy outcomes of interest was recurrent stroke (hemorrhagic or ischemic) with DAPT compared with aspirin monotherapy. Primary safety outcome was the occurrence of major bleeding, defined as any bleed that resulted in hemodynamic compromise, hypovolemic shock requiring an intervention, requirement of blood transfusion, or symptomatic intracranial hemorrhage. Table I in the Data Supplement addresses the different definitions of major bleeds across the included trials. Secondary outcomes of interest were risk of any ischemic stroke, hemorrhagic stroke, all-cause death, and major adverse cardiovascular events (MACE), defined as a composite of myocardial infarction, any stroke, and cardiovascular death.

Statistical Analysis

We calculated pooled risk ratios (RRs) using a random-effects model.[7] A random-effects model was used to account for interstudy heterogeneity due to variation in the included population. Heterogeneity among studies was assessed using the Higgins I2 value.[8] I2 values of 25%, 50%, and 75% were considered to represent low, moderate, and high levels of heterogeneity, respectively. We conducted a meta-regression analysis using mixed-effects modeling to explain any heterogeneity observed secondary to the duration of DAPT in the intervention arm of each trial. To address heterogeneity secondary to differences in the duration of follow-up, we pooled prespecified hazard ratios and the 95% CI for the primary efficacy and safety outcomes. Publication bias was assessed visually with funnel plots. All P values were 2-tailed with statistical significance specified at 0.05 and CI reported at 95% level. Stata version 16 and R package, metafor, version 3.6.2 (R Foundation) were used for analyses. This study was reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses amendment to the Quality of Reporting of Meta-analyses statement.