Efficacy and safety of aspirin plus clopidogrel versus aspirin alone in ischemic stroke or high-risk transient ischemic attack: A meta-analysis of randomized controlled trials

Background: Antiplatelet therapy plays an important role in reducing the risk of stroke recurrence in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA). However, data regarding the effectiveness and safety of using aspirin plus clopidogrel in dual antiplatelet therapy (DAPT) compared to aspirin alone in mild ischemic stroke is limited. Methods: PubMed/MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared DAPT to aspirin alone started within 72 hours in mild ischemic stroke or high-risk TIA. We used a random effects model to pool risk ratios (RRs) along with 95% CIs for clinical outcomes. Results: Four RCTs with 16,547 patients were included in this study. DAPT significantly reduced the risk of recurrent stroke by 26% (RR: 0.74; 95% CI: 0.67–0.83; p < 0.00001), ischemic stroke by 28% (RR: 0.72; 95% CI: 0.65–0.80; p < 0.00001), and major adverse cardiovascular events (MACE) by 24% (RR: 0.76; 95% CI: 0.68–0.84; p < 0.00001) compared to aspirin monotherapy. However, DAPT was associated with a significantly increased risk of moderate or severe bleeding (RR: 1.88; 95% CI: 1.10–3.23; p = 0.02) compared to aspirin alone. No significant differences were observed for hemorrhagic stroke (RR: 1.77; 95% CI: 0.96–3.29; p = 0.07), all-cause mortality (RR: 1.25; 95% CI: 0.87–1.80; p = 0.23), cardiovascular mortality (RR: 1.38; 95% CI: 0.81–2.33; p = 0.23), and myocardial infarction (RR: 1.63; 95% CI: 0.77–3.46; p = 0.20). Conclusion: DAPT involving aspirin plus clopidogrel reduces stroke recurrence and MACE but can lead to an increased risk of moderate or severe bleeding compared to aspirin monotherapy. (PROSPERO ID: CRD42024499310)