Safety and efficacy of different P2Y12 inhibitors in patients with acute coronary syndromes stratified by the PRAISE risk score: a multi-center 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 ischemic and bleeding risk estimated with a machine learning (ML)-derived model (PRAISE score). Methods and results: Incidences of death, re-acute myocardial infarction (re-AMI) and BARC 3-5 bleeding with aspirin plus different P2Y12 inhibitors (clopidogrel or potent P2Y12 inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE dataset grouped in four sub-cohorts: low-to-moderate ischemic and bleeding risk; low-to-moderate ischemic risk and high bleeding risk; high ischemic risk and low-to-moderate bleeding risk; high ischemic 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 ischemic risk (HR 1.69, 95% 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 ischemic risk compared to prasugrel or ticagrelor, without 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 ischemic risk. Conclusions: Among ACS patients with non-high risk of bleeding, the use of potent P2Y12 inhibitors is associated with a lower risk or death and recurrent ischemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel.