Monotherapy with a P2Y₁₂ inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis

Background: Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y₁₂ inhibitor versus aspirin for secondary prevention.

Methods: In this systematic review and meta-analysis, all randomised trials comparing P2Y₁₂ inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y₁₂ inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I² index. This study is registered with PROSPERO (CRD42018115037).

Findings: A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y₁₂ inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y₁₂ inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I²=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I²=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I²=0%), and vascular death (OR 0·97 [0·86-1·09]; I²=0%) did not differ between patients who received a P2Y₁₂ inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I²=3·9%) did not differ between patients who received a P2Y₁₂ inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y₁₂ inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y₁₂ inhibitor used.

Interpretation: Compared with aspirin monotherapy, P2Y₁₂ inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y₁₂ inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality.

Funding: Italian Ministry of Education.