Prevalence and risk of inappropriate dosing of direct oral anticoagulants in two Swiss atrial fibrillation registries

Background: Direct oral anticoagulants (DOACs) have a favourable risk-benefit profile compared to vitamin K-antagonists (VKAs) in atrial fibrillation (AF). Dosing is based on age, weight and renal function, without need of routine monitoring.Methods and results: In two prospective, multicentre AF cohorts (Swiss-AF, BEAT-AF) patients were stratified as receiving VKAs or adequately-, under-or overdosed DOACs, according to label. Primary outcome was a com-posite of major adverse clinical events (MACE), defined as cardiovascular death, myocardial infarction (MI), ischaemic stroke and systemic embolism. Secondary outcomes included major bleeding. Adjustment for con-founding was performed. Median follow-up was 4 years.Of 3236 patients, 1875 (58%) were on VKAs and 1361 (42%) were on DOACs, of which 1137 (83%) were adequately-, 134 (10%) over-and 90 (7%) under-dosed. Compared to adequately dosed individuals, overdosed patients were more likely to be older and female. Underdosing correlated with concomitant aspirin therapy and coronary artery disease. Both groups had higher CHA2DS2-VASc scores. Patients on overdosed DOACs had higher incidence of MACE (HR 1.75; CI 1.10-2.79; adjusted-HR: 1.22) and major bleeding (HR 1.99; CI 1.14-3.48; adjusted-HR: 1.51). Underdosing was not associated with a higher incidence of MACE (HR 0.94; CI 0.46-1.92; adjusted-HR 0.61) or major bleeding (HR 1.07; CI 0.46-2.46; adjusted-HR 0.82). After adjustment, all CIs crossed 1.0.Conclusion: Inappropriate DOAC-dosing was more prevalent in multimorbid patients, but did not correlate with higher risks of adverse events after adjusting for confounders. DOAC prescription should follow label.