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Multiple guidelines and consensus papers have addressed the role of antithrombotic strategies in patients with established coronary artery disease (CAD). Since evidence and terminology continue to evolve, the European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association for Acute Cardiovascular Care (ACVC) and European Association of Preventive Cardiology (EAPC) undertook a consensus initiative to guide clinicians to select the optimal antithrombotic regimen for each patient. The aim of this document is to provide an update for clinicians on best antithrombotic strategies in patients with established CAD, classifying each treatment option in relation to the number of antithrombotic drugs irrespective of whether the traditional mechanism of action is expected to mainly inhibit platelets or coagulation cascade. With the aim to reach comprehensiveness of available evidence, we systematically reviewed and performed meta-analyses by means of both direct and indirect comparisons to inform the present consensus document.

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. Methods and results Forty-three (N = 189 261 patients) 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.

Background Bleeding is the principal safety concern of antithrombotic therapy and occurs frequently among patients with coronary artery disease (CAD). Aims We aim to evaluate the prognostic impact of bleeding on mortality compared with that of myocardial infarction (MI) in patients with CAD. Methods We searched Medline and Embase for studies that included patients with CAD and that reported both, the association between the occurrence of bleeding and mortality, and between the occurrence of MI and mortality within the same population. Adjusted hazard ratios (HRs) for mortality associated with bleeding and MI were extracted and ratio of hazard ratios (rHRs) were pooled by using inverse variance weighted random effects meta-analyses. Early events included periprocedural or within 30-day events after revascularization or acute coronary syndrome (ACS). Late events included spontaneous or beyond 30-day events after revascularization or ACS. Results 141,059 patients were included across 16 studies and 128,660 (91%) underwent percutaneous coronary intervention. Major bleeding increased the risk of mortality to the same extent of MI (ratioHR bleedingvsMI 1.10, 95% CI, 0.71–1.71, P=0.668). Early bleeding was associated with a higher risk of mortality than early MI (ratioHR bleedingvsMI 1.46, 95% CI, 1.13–1.89, P=0.004), although this finding was not present when only randomized trials were included. Late bleeding was prognostically comparable to late MI (ratioHR bleedingvsMI 1.14, 95% CI, 0.87–1.49, P=0.358). Conclusions Compared with MI, major and late bleeding is associated with a similar increase in mortality, whereas early bleeding might have a stronger association with mortality. Impact on daily practice. Major and late bleeding should be considered prognostically equivalent to MI, given the similar association with mortality. Early bleeding has even a stronger association with mortality than early MI, emphasizing the importance of bleeding avoidance strategies among patients undergoing PCI. Funding Acknowledgement Type of funding sources: None. Visual AbstractBleeding vs MI risk of mortality