Efficacy and Safety of Direct‐Acting Oral Anticoagulants in Atrial Fibrillation With Hypertrophic Cardiomyopathy

Background Patients with hypertrophic cardiomyopathy (HCM) were excluded from pivotal trials comparing the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists. Methods Our retrospective cohort study using the TriNetX database compared adults with HCM‐atrial fibrillation who initiated DOACs or vitamin K antagonists. The primary outcomes were all‐cause mortality and ischemic stroke/systemic thromboembolism. Secondary outcomes included major bleeding, intracranial hemorrhage, gastrointestinal bleeding, and all‐cause hospitalization. Subgroup analysis was conducted for obstructive HCM. Results Among 13 143 patients with HCM‐atrial fibrillation (2963 matched pairs). DOAC use was associated with lower all‐cause mortality (hazard ratio HR, 0.82 95% CI, 0.73–0.93; P <0.001), major bleeding (HR, 0.85 95% CI, 0.73–0.99; P =0.03), and intracranial hemorrhage (HR, 0.54 95% CI, 0.36–0.79; P =0.001) compared with vitamin K antagonists. No differences were observed in the rates of ischemic stroke (HR, 0.94 95% CI, 0.73–1.2; P =0.6) or the composite of stroke or systemic thromboembolism (HR, 0.87 95% CI, 0.69–1.10; P =0.25), gastrointestinal bleeding (HR, 0.97 95% CI, 0.77–1.22; P =0.82), or all‐cause hospitalizations (HR, 1.07 95% CI, 0.93–1.07; P =0.051). In the subgroup with obstructive HCM, DOAC use was associated with a reduced risk of all‐cause mortality (HR, 0.80 95% CI, 0.66–0.99; P =0.035) and major bleeding (HR, 0.76 95% CI, 0.61–0.96; P =0.02) without stroke or thromboembolic risk reduction (HR, 0.69 95% CI, 0.47–1.01; P =0.05). Conclusions Among patients with HCM‐atrial fibrillation, DOACs were associated with lower mortality and bleeding risk compared with vitamin K antagonists, with no increased risk of stroke or systemic thromboembolism.