Switching From Aspirin Monotherapy After Noncardioembolic Stroke: A Systematic Review and Network Meta-Analysis

BACKGROUND: Patients who experience an ischemic stroke while on aspirin therapy present a clinical dilemma about optimal long-term secondary prevention. While switching to an alternative antithrombotic agent is often considered, the effectiveness of switching remains uncertain. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials reporting outcomes among patients with ischemic stroke while on aspirin and were either continued on aspirin or switched to an alternative antithrombotic therapy. Alternative antithrombotics included 2 trials of vitamin K antagonists (n=478), 3 trials of dual antiplatelet therapy (n=2229), 3 trials of direct oral anticoagulant (n=2660) monotherapy, and 1 trial of low-dose direct oral anticoagulant added onto aspirin (n=92). We excluded trials of patients with only short-term outcomes of 90 days or fewer, or those with cardioembolic sources of stroke requiring anticoagulation. Our primary outcome was recurrent ischemic stroke; the secondary outcome was a composite of ischemic stroke, myocardial infarction, and vascular death (or all-cause mortality). Outcomes reflect recurrent events measured over a median of ≈19 months (range 11–42 months). In the network portion of this meta-analysis, surface under the cumulative ranking curve rankings and pairwise meta-analyses were used to evaluate and compare the relative efficacy of alternative antithrombotic medications. RESULTS: Data were available from 9 studies (total N=5459 patients) for the outcome of recurrent ischemic stroke. Switching to another therapy was associated with a pooled relative risk of recurrent stroke of 0.88 (95% CI, 0.76–1.03) compared with continuing aspirin, with minimal heterogeneity ( P =0.93; I ²=0). For the composite secondary outcome, 6 studies contributed data, yielding a pooled relative risk of 0.89 (95% CI, 0.72–1.10). In the network meta-analysis, dabigatran, apixaban, and aspirin+low-dose rivaroxaban ranked the highest among antithrombotic alternatives to aspirin, though none were significantly better than continuing aspirin. Rankings were similar when based on posterior estimates from the clinical trials and when using predictive distributions that incorporate between-study variance (ie, expected performance in future settings). CONCLUSIONS: Among patients experiencing ischemic stroke while taking aspirin, switching to an alternative antithrombotic therapy was not conclusively associated with a reduction in recurrent stroke and composite cardiovascular events. Trials are needed to determine whether specific antithrombotic strategies meaningfully improve outcomes in this high-risk population.