Diabetes Mellitus (DM) is a common comorbidity in patients hospitalized for acute coronary syndrome (ACS) of increasing prevalence over the last decade, associated with higher mortality. In addition to higher platelet reactivity, the altered metabolic activation from clopidogrel in DM patients contributes to a suboptimal antiplatelet response. This is why potent P2Y12 receptor inhibitors are recommended after percutaneous coronary intervention (PCI) in patients with ACS and DM, given its consistent and favorable risk-benefit profile.
The current guidelines recommend 12 month of dual antiplatelet therapy (DAPT) and do not support short or de-escalation strategies for DM patients. However, recent clinical trials have assessed P2Y12 inhibitor monotherapy after short DAPT, and have shown reduced major bleeding events with no increased cardiovascular events rate, regardless DM status. These studies have mainly focused on ticagrelor monotherapy.
Recent data from Japanese cohorts of ACS or chronic coronary syndrome (CCS) patients suggest clopidogrel monotherapy after one-month DAPT, vs. A 12 month DAPT scheme, reduces bleeding risk with no increase in ischemic events, in DM patients undergoing PCI. Likewise, the TALOS-AMI trial (Ticagrelor versus Clopidogrel in Stabilized Acute Myocardial Infarction Patients) has shown significant reduction of bleeding risk using early unguided DAPT de-escalation in AMI patients with consistent results across diverse subpopulations.
The aim of this study was to conduct a subgroup analysis focusing on DM patients with ACS to assess the safety and efficacy of clopidogrel-based DAPT with early de-escalation, with concomitant aspirin as alternative strategy.
The primary outcome was clinical adverse events, as a composite of cardiovascular death, AMI, stroke, and type 2,3, or 5 BARC bleeding. Secondary outcomes included the separate ischemic and bleeding components.
Of a total 2,697 patients, 31.9 % presented DM. 420 of these patients were de-escalated and 439 make part of the control group. Patients were mostly men, mean age 61. Complex PCI was performed in 408 DM patients (47.5 %), including multivessel interventions in 301 cases (35.0 %). De-escalation strategy was consistently associated with lower primary outcome incidence vs. continuation with ticagrelor, mainly at the expense of reduced BARC 2 bleeding events, regardless DM status.
In DM patients, the differences in bleeding (HR: 0.48; 95% CI: 0.22–1.05; p = 0.066) and ischemic outcomes (HR: 0.57; 95% CI: 0.25–1.29; p = 0.176) did not reach statistical significance. Results were consistent across subgroups stratified by glycemic control and PCI complexity. Significant interactions were observed between treatment and DM presence for BARC 3 or 5 bleeding (p = 0.042) and target-vessel revascularization (p = 0.014).
Conclusion
Unguided de-escalation to clopidogrel after one-month ticagrelor-based DAPT significantly reduced clinical adverse events in AMI-DM patients undergoing PCI, manly by reducing minor bleeding events, with no concomitant increase in global bleeding events. However, these findings should be considered as hypothesis generators and support the need for larger prospective studies, especially to assess fatal bleeding risk or repeat revascularization.
Original Title: De-Escalation Dual Antiplatelet Strategy in Stabilized Myocardial Infarction Patients With Diabetes Mellitus.
Reference: Sang Hyun Kim, MD, PHD et al JACC Cardiovasc Interv. 2025;18:2713–2724.
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