DOAC monotherapy versus DOAC/clopidogrel combination therapy after DES implantation in AF
AHA 2025 – In ADAPT AF-DES among AF patients with drug-eluting stent (DES) implantation ≥1 year prior, DOAC monotherapy was noninferior to DOAC plus clopidogrel combination therapy in reducing a composite outcome of ischemic and bleeding events at 12 months.
This summary is based on the presentation of Jung-Sun Kim, MD, PhD (Seoul, South Korea) at the AHA Scientific Sessions 2025 - Appropriate Duration of Antiplatelet and Thrombotic Strategy after 12 Months in Patients with Atrial Fibrillation Treated with Drug-Eluting Stents (ADAPT AF-DES).
Introduction and methods
In AF patients stabilized after implantation of a drug-eluting stent (DES), current guidelines recommend DOAC monotherapy >1 year after the PCI. However, randomized data supporting this approach are limited. The ADAPT AF-DES (Appropriate Duration of Antiplatelet and Thrombotic Strategy After 12 Months in Patients With Atrial Fibrillation Treated With Drug-Eluting Stents) trial was designed to assess whether DOAC monotherapy is noninferior to combination therapy with DOAC and clopidogrel in AF patients with stable coronary artery disease >1 year after DES implantation. In this multicenter, open-label, noninferiority, phase 4 RCT conducted in in South Korea, 960 AF patients (aged 19–85 years) with CHA₂DS₂-VASc score ≥2 who had undergone DES implantation ≥1 year prior were randomized to DOAC monotherapy or DOAC plus clopidogrel combination therapy. The primary endpoint was the incidence of net adverse clinical events, a composite outcome of all-cause mortality, MI, stent thrombosis, stroke, systemic embolism, or major bleeding or clinically relevant nonmajor bleeding events (as defined by the International Society on Thrombosis and Haemostasis criteria), at 12 months. The noninferiority margin was 3.0 percentage points. Secondary endpoints included the individual components of the primary endpoint at 12 months and net adverse clinical events at 24 months.
Main results
- At 12 months, the cumulative incidence of the primary endpoint was 9.6% in patients treated with DOAC monotherapy (n=482) and 17.2% in those assigned to combination therapy (n=478) (absolute difference: –7.6 percentage points; 95.2%CI: −11.9 to −3.3; P<0.001 for noninferiority; HR: 0.54; 95.2%CI: 0.37–0.77; P<0.001 for superiority).
- The key secondary endpoint of major bleeding or clinically relevant nonmajor bleeding events at 12 months occurred in 25 patients (5.2%) in the DOAC monotherapy group and 63 patients (13.2%) in the combination-therapy group (HR: 0.38; 95%CI: 0.24–0.60).
- The rate of CV death, MI, stent thrombosis, ischemic stroke, or systemic embolism at 12 months was 3.3% in the DOAC monotherapy group and 4.0% in the combination-therapy group (HR: 0.84; 95%CI: 0.43–1.63).
- Subgroup analysis showed consistent results across subgroups stratified by, among others, age, sex, DES generation, or type of DOAC.
Conclusion
In AF patients who had undergone DES implantation ≥1 year prior, DOAC monotherapy was noninferior to DOAC plus clopidogrel combination therapy in the reduction of net adverse clinical events, including ischemic and bleeding events, at 12 months. Prespecified analysis showed DOAC monotherapy was also superior to combination therapy for this composite outcome. Additionally, DOAC monotherapy reduced the risk of major bleeding or clinically relevant nonmajor bleeding events compared with combination therapy. Dr. Kim noted that the follow-up period of 1 year was relatively short, but that “prespecified secondary analyses with extended follow-up >2 years are currently ongoing.”
- Our reporting is based on the information provided at the AHA Scientific Sessions 2025 -