De-escalation from ticagrelor to clopidogrel in patients with acute myocardial infarction: the TALOS-AMI HBR substudy

Background: The benefits of de-escalation of P2Y12 inhibition after percutaneous coronary intervention (PCI) may differ by high bleeding risk (HBR) status. Aims: We investigated the efficacy and safety of de-escalation from ticagrelor to clopidogrel after PCI by HBR status. Methods: This is a non-prespecified post hoc analysis of the TicAgrelor Versus CLOpidogrel in Stabilized Patients with Acute Myocardial Infarction (TALOS-AMI) trial. Net adverse clinical events (a composite of cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium [BARC] bleeding type 2, 3, or 5) at 1 year post-PCI were compared between the de-escalation (clopidogrel plus aspi-rin) and the active control (ticagrelor plus aspirin) groups by HBR status, as defined by the modification of the Academic Research Consortium (ARC) criteria. Results: A total of 2,625 patients in the TALOS-AMI trial were analysed. Of these, 589 (22.4%) met the modified ARC-HBR criteria. The de-escalation group had lower primary endpoint rates than the control group in both HBR (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.26-0.84) and non-HBR (HR 0.59, 95% CI: 0.41-0.84) patients. There were no differences in treatment effect for the primary endpoint regardless of HBR status (p for interaction=0.904). BARC bleeding type 3 or 5 was less common in the de-escalation than the control group among HBR patients only (HR 0.24, 95% CI: 0.07-0.84). Conclusions: In stabilised acute myocardial infarction patients, unguided de-escalation from ticagrelor to clopidogrel was associated with a lower rate of net adverse clinical outcomes irrespective of HBR status. The effect of de-escalation of P2Y12 inhibition on reducing haemorrhagic events was greater in patients with HBR.