Antithrombotic Therapy in Atrial Fibrillation Patients with Prior Complex Percutaneous Coronary Intervention: A Secondary Analysis of the Randomized ADAPT AF-DES Trial

BackgroundIn patients with atrial fibrillation (AF) and stable coronary artery disease beyond 1 year after percutaneous coronary intervention (PCI), oral anticoagulant monotherapy is guideline-recommended; however, its efficacy and safety in patients with complex PCI remain uncertain. MethodsWe conducted a post-hoc analysis of the randomized ADAPT AF-DES trial comparing NOAC monotherapy versus NOAC plus clopidogrel in AF patients [≥]12 months after second- or third-generation drug-eluting stent implantation. Complex PCI was defined by one of the following characteristics: [≥]3 stents, [≥]3 lesions, bifurcation with 2 stents, total stent length [≥]60 mm, left main PCI, or chronic total occlusion PCI. Net adverse clinical events (NACE), ischemic composite outcomes, and bleeding composite outcomes were evaluated according to PCI complexity. ResultsAmong 960 patients, 247 (25.7%) underwent complex PCI and 713 (74.3%) underwent noncomplex PCI. NOAC monotherapy was associated with a lower risk of NACE compared with combination therapy in both the complex PCI group (9.5% vs 21.5%; hazard ratio 0.42, 95% confidence interval 0.21-0.83; P=0.01) and the noncomplex PCI group (9.6% vs 15.7%; hazard ratio 0.59, 95% confidence interval 0.39-0.90; P=0.02), with no significant interaction. Ischemic outcomes did not differ significantly between treatment strategies regardless of PCI complexity, whereas bleeding outcomes were consistently lower with NOAC monotherapy in both complex and noncomplex PCI groups. ConclusionsIn this post hoc analysis of the randomized ADAPT AF-DES trial, the clinical benefits of NOAC monotherapy beyond 12 months after PCI--characterized by reduced bleeding without a significant increase in ischemic events--were consistent regardless of PCI complexity. While hypothesis-generating, these findings support a long-term antithrombotic strategy prioritizing bleeding reduction in patients with AF, irrespective of prior PCI complexity. Trial registrationURL: http://www.clinicaltrials.gov; Unique identifier: NCT04250116. Clinical perspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIIn a randomized population of patients with AF and prior drug-eluting stent implantation, the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel were evaluated according to anatomic PCI complexity. C_LIO_LIAmong patients with prior complex PCI, NOAC monotherapy was not associated with an increased risk of ischemic events and was associated with a substantial reduction in bleeding. C_LI What are the clinical implications?O_LINOAC monotherapy beyond 1 year after PCI was supported in patients with AF, including those with prior complex PCI. C_LIO_LILong-term antithrombotic decisions may place greater emphasis on bleeding risk than PCI complexity. C_LIO_LIThe optimal duration of combination antithrombotic therapy after complex PCI in patients with AF remains to be determined. C_LI