P2Y12 inhibitors plus aspirin versus aspirin alone in patients with ischemic cerebrovascular events: An updated meta-analysis of randomized controlled trials

J Stroke Cerebrovasc Dis. 2025 Jan 2;34(2):108180. doi: 10.1016/j.jstrokecerebrovasdis.2024.108180. Online ahead of print.

Abstract

Background: The efficacy and safety of P2Y12 inhibitors (P2Y12i) with aspirin in patients with non-cardioembolic ischemic cerebrovascular events remains a topic of ongoing debate. Therefore, we conducted an updated meta-analysis to compare these drugs with aspirin alone.

Methods: We systematically searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing the two treatment regimens in patients with ischemic cerebrovascular events. Primary outcomes were all-cause mortality, severe bleeding, and stroke recurrence. We performed subgroup analyses stratified by National Institutes of Health Stroke Scale (NIHSS). Risk ratios (RRs) with 95 % confidence intervals were calculated using a random effects model. R software (version 4.3.2) was used for statistical analyses.

Results: Fifteen studies were included, comprising 38,851 patients, of whom 19,483 (50.1 %) received P2Y12i plus aspirin. Follow-up ranged from 7 days to 3.4 years. P2Y12i plus aspirin significantly reduced stroke recurrence (RR 0.78; 95 % CI = 0.71-0.87; p < 0.05), but increased the incidence of all-cause mortality (RR 1.38; 95 % CI = 1.11-1.72; p < 0.05) and severe bleeding (RR 2.07; 95 % CI 1.61 to 2.66; p > 0.05) compared with aspirin. There was no significant difference between groups in all-cause mortality in patients with NIHSS ≤3 or ≤10.

Conclusion: P2Y12i plus aspirin reduced stroke recurrence, but increased all-cause mortality and severe bleeding in patients with non-cardioembolic ischemic events. There was no difference between groups in all-cause mortality in patients with NIHSS scores ≤3 or ≤10.

Keywords: Aspirin; Ischemic stroke; Meta-analysis; P2Y12 inhibitors; TIA.