Ticagrelor for stroke prevention in patients with vascular risk factors: A systematic review and meta-analysis

Background Even though ticagrelor was beneficial in prior cardiovascular trials, its efficacy in stroke prevention was inconclusive in recent randomized-controlled clinical trials (RCTs). We sought to consolidate the evidence for efficacy and safety of ticagrelor for stroke prevention. Methods: We conducted a systematic review and meta-analysis of RCTs in major databases reporting following efficacy and safety outcomes among patients with cerebral or cardiovascular risk factors treated with ticagrelor (vs. control): ischemic stroke (IS), combined ischemic and hemorrhagic stroke, myocardial infarction (MI), cardiovascular death (CVD), all-cause mortality, and major bleeding events. We pooled risk ratios (RR) and adjusted hazard ratios (HRadjusted) from each trial using random-effect models, and assessed the heterogeneity using Cochran Q and I-2 statistics. Results: We identified 13 RCTs, comprising 64,360 patients. In comparison to control group, ticagrelor reduced the risk of IS (RR = 0.86; 95%CI = 0.78-0.95, p = .003; I-2 = 0%), combined ischemic and hemorrhagic strokes (risk ratio: 0.90; 95%CI: 0.81-1.00, p = .05; I-2 = 0%), and composite stroke/MI/CVD (RR = 0.90; 95%CI = 0.81-0.99, p =.03; I-2 = 47%). Ticagrelor was not associated with increased risk of mortality (RR: 0.95; 95%CI: 0.84-1.07; p = .40) or major bleeding events (RR: 1.18; 95%CI: 0.92-1.50; p =.19). Additional analyses demonstrated that ticagrelor reduced the risk of incident strokes (HRadjusted = 0.87; 95%CI = 0.76-0.98; p = .03) and composite stroke/MI/CVD (HRadjusted = 0.88; 95%CI = 0.78-0.98; p = .02) among patients with prior history of IS or transient ischemic attack. Conclusions: Ticagrelor seems to be a beneficial option for primary and secondary stroke prevention in patients with cerebral or cardiovascular risk factors. Further RCTs are needed to evaluate the role of ticagrelor in secondary stroke prevention.