P2Y12 inhibitors plus aspirin for acute treatment and secondary prevention in minor stroke and high-risk transient ischemic attack: A systematic review and meta-analysis

Background: Aspirin is a cornerstone of preventive treatment for stroke recurrence, but during the last few years the role of dual antiplatelet therapy (DAPT) is much more emerging.Objective: This systematic review aimed to compare early use of P2Y12 inhibitors (clopidogrel/ticagrelor) plus aspirin to aspirin alone for acute treatment and secondary prevention in acute non-cardioembolic minor ischemic stroke or TIA.Methods: A systematic search on MEDLINE and EMBASE was performed. Treatment effects were estimated with RRs and 95% CI. We used RevMan 5.4 for data analyses. We assessed methodological quality of selected studies according to Rob2 tools and quality of evidence with GRADE approach.Results: Four RCTs were included, enrolling 21,459 patients. Compared to aspirin alone, DAPT was superior in reducing stroke recurrence (RR 0.74, 95% CI 0.67-0.82, P<0.00001, absolute risk difference by 2%, NNT 50) and disabling stroke defined as mRS>2 (RR 0.84, 95% CI 0.75-0.95, P=0.004), with no impact on all causes of mortality (RR 1.30, 95% CI 0.90-1.89, P=0.16). An increased risk of major bleeding was emerged (RR 2.54, 95% CI 1.65-3.92, P<0.0001, absolute risk difference by 0,4%, NNH 250), in particular with ticagrelor, but there was no correlation between therapy duration and bleeding risk, as appeared from one-month (RR 3.06, 95% CI 1.64 to 5.69) and three-month (RR 2.09, 95% CI 1.18 to 3.69) follow-up analysis.Conclusions: Early administration of P2Y12 inhibitors plus aspirin in patients with acute non-cardioembolic minor ischemic stroke or TIA reduced the incidence of ischemic stroke recurrence, impacting more significantly than the increased bleeding risk and influencing patients' quality of life by reducing disabling stroke.