Abstract
PURPOSE: Small subcortical infarction (SSI) accounts for approximately 25% of ischemic strokes and shares a comparable recurrence rate of cardiovascular events with other stroke subtypes. This study aimed to evaluate the efficacy and safety of various antiplatelet for secondary prevention of SSI by network meta-analysis (NMA). METHODS: We systematically searched Medline, Embase, Cochrane Library, and Web of Science from inception to October 2024 for randomized controlled trials (RCTs). Efficacy outcomes included: incidence of major adverse cardiovascular events (MACEs), rates of any stroke and ischemic stroke recurrence. Safety outcomes included: incidence of intracranial hemorrhage, severe bleeding, any bleeding events, and mortality. FINDINGS: A total of 24 RCTs involving 47,507 SSI patients were included in systematic review. The NMA included 19 RCTs (39,137 patients). The NMA demonstrated that Cilostazol showed the best efficacy in preventing MACEs (surface under the cumulative ranking curve (SUCRA): 90.0%). cilostazol significantly reduced the incidence of MACEs compared to aspirin (OR, 0.66; 95% CI, 0.49-0.89), ticlopidine (OR, 0.65; 95% CI, 0.43-1.00), dipyridamole (OR, 0.61; 95% CI, 0.42-0.90), vorapaxar (OR, 0.51; 95% CI, 0.35-0.74), Sarpogrelate (OR, 0.62; 95% CI, 0.40-0.97), and placebo (OR, 0.51; 95% CI, 0.37-0.71). Regarding safety, aspirin plus clopidogrel and vorapaxar was associated with a significantly increased risk of severe bleeding events compared to the control. DISCUSSION AND CONCLUSIONS: Cilostazol may be the most effective agent for preventing cardiovascular event recurrence. Aspirin plus clopidogrel and vorapaxar may be not recommended due to heightened bleeding risks. REGISTRATION: International prospective register of systematic reviews (PROSPERO) - CRD42024607819.