Within and beyond 12-month efficacy and safety of antithrombotic strategies in patients with established coronary artery disease. Two companion network meta-analyses of the 2022 joint clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association for Acute CardioVascular Care (ACVC) and European Association of Preventive Cardiology (EAPC)

Abstract Aims To appraise all available antithrombotic treatments within or after 12 months following coronary revascularization and/or acute coronary syndrome in two network meta-analyses (NMA). Methods and results Forty-three (N = 189 261) trials within 12 months and 19 (N = 139 086 patients) trials beyond 12 months were included for efficacy/safety endpoints appraisal. Within 12 months, ticagrelor 90 mg bis in die (b.i.d.) (hazard ratio [HR] 0.66; 95% confidence interval [CI]: 0.49–0.88), aspirin and ticagrelor 90 mg (HR 0.85; 95%CI: 0.76–0.95), or aspirin, clopidogrel and rivaroxaban 2.5 mg b.i.d. (HR 0.66; 95%CI: 0.51–0.86) were the only treatments associated with lower cardiovascular mortality, compared with aspirin and clopidogrel, without or with greater bleeding risk for the first and the other treatment options, respectively. Beyond 12 months, no strategy lowered mortality; compared with aspirin; the greatest reductions of myocardial infarction (MI) were found with aspirin and clopidogrel (HR 0.68; 95%CI, 0.55–0.85) or P2Y12 inhibitor monotherapy (HR 0.76; 95%CI, 0.61–0.95), especially ticagrelor 90 mg (HR 0.54; 95%CI, 0.32–0.92), and of stroke with VKA (HR, 0.56; 95%CI, 0.44–0.76) or aspirin and rivaroxaban 2.5 mg (HR, 0.58; 95%CI, 0.44–0.76). All treatments increased bleeding except P2Y12 monotherapy, compared with aspirin. Conclusion Within 12 months, ticagrelor 90 mg monotherapy was the only treatment associated with lower mortality, without bleeding risk trade-off compared with aspirin and clopidogrel. Beyond 12 months, P2Y12 monotherapy, especially ticagrelor 90 mg, was associated with lower MI without bleeding trade-off; aspirin and rivaroxaban 2.5 mg most effectively reduced stroke, with a more acceptable bleeding risk than VKA, compared with aspirin. Registration URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifiers: CRD42021243985 and CRD42021252398.