Abbreviated or Standard Dual Antiplatelet Therapy by Sex in Patients at High Bleeding Risk: A Prespecified Secondary Analysis of a Randomized Clinical Trial

Abstract

Importance: Abbreviated dual antiplatelet therapy (DAPT) reduces bleeding with no increase in ischemic events in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI).

Objectives: To evaluate the association of sex with the comparative effectiveness of abbreviated vs standard DAPT in patients with HBR.

Design, setting, and patients: This prespecified subgroup comparative effectiveness analysis followed the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated vs Standard DAPT Regimen (MASTER DAPT) trial, a multicenter, randomized, open-label clinical trial conducted at 140 sites in 30 countries and performed from February 28, 2017, to December 5, 2019. A total of 4579 patients with HBR were randomized at 1 month after PCI to abbreviated or standard DAPT. Data were analyzed from July 1 to October 31, 2022.

Interventions: Abbreviated (immediate DAPT discontinuation, followed by single APT for ≥6 months) or standard (DAPT for ≥2 additional months, followed by single APT for 11 months) treatment groups.

Main outcomes and measures: One-year net adverse clinical events (NACEs) (a composite of death due to any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (MACCEs) (a composite of death due to any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding (MCB).

Results: Of the 4579 patients included in the analysis, 1408 (30.7%) were women and 3171 (69.3%) were men (mean [SD] age, 76.0 [8.7] years). Ischemic and bleeding events were similar between sexes. Abbreviated DAPT was associated with comparable NACE rates in men (hazard ratio [HR], 0.97 [95% CI, 0.75-1.24]) and women (HR, 0.87 [95% CI, 0.60-1.26]; P = .65 for interaction). There was evidence of heterogeneity of treatment effect by sex for MACCEs, with a trend toward benefit in women (HR, 0.68 [95% CI, 0.44-1.05]) but not in men (HR, 1.17 [95% CI, 0.88-1.55]; P = .04 for interaction). There was no significant interaction for MCB across sex, although the benefit with abbreviated DAPT was relatively greater in men (HR, 0.65 [95% CI, 0.50-0.84]) than in women (HR, 0.77 [95% CI, 0.53-1.12]; P = .46 for interaction). Results remained consistent in patients with acute coronary syndrome and/or complex PCI.

Conclusions and relevance: These findings suggest that women with HBR did not experience higher rates of ischemic or bleeding events compared with men and may derive particular benefit from abbreviated compared with standard DAPT owing to these numerically lower rates of events.

Trial registration: ClinicalTrials.gov Identifier: NCT03023020.

Figure 1.. Net Adverse Clinical Events, Major Adverse Cardiac or Cerebral Events, and Major or Clinically Relevant Nonmajor Bleeding

DAPT indicates dual antiplatelet therapy; HR, hazard ratio.

Figure 2.. Main Outcomes of Abbreviated vs Standard Dual Antiplatelet Therapy (DAPT) in Male and Female Patients

Abbreviated and standard DAPT were compared by sex subgroups, with hazard ratios and 95% CIs for the 3 coprimary outcomes and their components (all-cause death, myocardial infarction, stroke, and Bleeding Academic Research Consortium [BARC] type 3 or 5). MACCE indicates major adverse cardiac and cerebral event; MCB, major or clinically relevant nonmajor bleeding; and NACE, net adverse clinical event.

Figure 3.. Interaction Between Sex and Dual Antiplatelet Therapy (DAPT) on Coprimary Efficacy Outcomes in the Overall Cohort and Stratified by Clinical Indication for Oral Anticoagulation (OAC)

The x-axis shows the categories of the patients according to sex and clinical indication for OAC; the y-axis shows event rates of the coprimary efficacy outcomes. HR indicates hazard ratio.