Safety and efficacy of different P₂Y₁₂ inhibitors in patients with acute coronary syndromes stratified by the PRAISE risk score: a multicentre study

Aims To establish the safety and efficacy of different dual antiplatelet therapy (DAPT) combinations in patients with acute coronary syndrome (ACS) according to their baseline ischaemic and bleeding risk estimated with a machine learning derived model [machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE) score]. Methods and Incidences of death, re-acute myocardial infarction (re-AMI), and Bleeding Academic Research Consortium 3–5 bleed-results ing with aspirin plus different P₂Y₁₂ inhibitors (clopidogrel or potent P₂Y₁₂ inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE data set grouped in four subcohorts: low-to-moderate ischaemic and bleeding risk; low-to-moderate ischaemic risk and high bleeding risk; high ischaemic risk and low-to-moderate bleeding risk; and high ischaemic and bleeding risk. Hazard ratios (HRs) for the outcome measures were derived with inverse probability of treatment weighting adjustment. Among patients with low-to-moderate bleeding risk, clopidogrel was associated with higher rates of re-AMI in those at low-to-moderate ischaemic risk [HR 1.69, 95% confidence interval (CI) 1.16–2.51; P = 0.006] and increased risk of death (HR 3.2, 1.45–4.21; P = 0.003) and re-AMI (HR 2.23, 1.45–3.41; P < 0.001) in those at high ischaemic risk compared with prasugrel or ticagrelor, without a difference in the risk of major bleeding. Among patients with high bleeding risk, clopidogrel showed comparable risk of death, re-AMI, and major bleeding vs. potent P₂Y₁₂ inhibitors, regardless of the baseline ischaemic risk. Conclusion Among ACS patients with non-high risk of bleeding, the use of potent P₂Y₁₂ inhibitors is associated with a lower risk of death and recurrent ischaemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel.