De-Escalation Dual Antiplatelet Strategy in Stabilized Myocardial Infarction Patients With Diabetes Mellitus

JACC Cardiovasc Interv. 2025 Nov 24;18(22):2713-2724. doi: 10.1016/j.jcin.2025.09.026.

Abstract

Background: Diabetes mellitus (DM) is associated with suboptimal clopidogrel response and elevated thrombotic risk. The benefit of early de-escalation of dual antiplatelet therapy (DAPT) in DM patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) remains uncertain.

Objectives: The authors sought to assess whether a 1-month, unguided de-escalation from ticagrelor to clopidogrel is associated with clinical benefit compared with continued ticagrelor-based DAPT in MI patients with DM.

Methods: This post hoc analysis included 859 patients with DM (31.9%) from the TALOS-AMI (Ticagrelor Versus Clopidogrel in Stabilized Patients With Acute Myocardial Infarction) trial who tolerated 1 month of ticagrelor-based DAPT post-PCI. Participants were randomized to continue ticagrelor or switch to clopidogrel for 11 months. The primary endpoint was a composite of ischemic (cardiovascular death, MI, and stroke), and bleeding (Bleeding Academic Research Consortium [BARC] type 2, 3, or 5 bleeding) endpoints.

Results: De-escalation was consistently associated with a lower incidence of primary endpoint compared with continued ticagrelor (mainly driven by fewer BARC type 2 bleeding events), irrespective of diabetes status (Pinteraction = 0.467). In the DM cohort, differences in bleeding (HR: 0.48; 95% CI: 0.22-1.05; P = 0.066) and ischemic (HR: 0.57; 95% CI: 0.25-1.29; P = 0.176) endpoints were not significant. Results were consistent across subgroups stratified by glycemic control and PCI complexity. Significant treatment-by-DM interactions were observed for BARC type 3 or 5 bleeding (Pinteraction = 0.042) and target vessel revascularization (Pinteraction = 0.014).

Conclusions: In MI patients with DM, 1-month unguided de-escalation to clopidogrel after ticagrelor-based DAPT was associated with clinical benefit without increasing ischemic risk. These results warrant further prospective validation.

Keywords: acute myocardial infarction; antiplatelet; clopidogrel; diabetes; ticagrelor.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Clopidogrel* / administration & dosage
  • Clopidogrel* / adverse effects
  • Diabetes Mellitus* / diagnosis
  • Diabetes Mellitus* / mortality
  • Drug Administration Schedule
  • Drug Substitution* / adverse effects
  • Dual Anti-Platelet Therapy* / adverse effects
  • Dual Anti-Platelet Therapy* / mortality
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction* / diagnostic imaging
  • Myocardial Infarction* / mortality
  • Myocardial Infarction* / therapy
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / mortality
  • Platelet Aggregation Inhibitors* / administration & dosage
  • Platelet Aggregation Inhibitors* / adverse effects
  • Risk Assessment
  • Risk Factors
  • Ticagrelor* / administration & dosage
  • Ticagrelor* / adverse effects
  • Time Factors
  • Treatment Outcome

Substances

  • Ticagrelor
  • Platelet Aggregation Inhibitors
  • Clopidogrel