Comparative effectiveness of warfarin, dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation: A nationwide pharmacoepidemiological study

• Published in: PloS one Vol. 14; no. 8; p. e0221500
• Main Authors: Kjerpeseth, Lars J., Selmer, Randi, Ariansen, Inger, Karlstad, Øystein, Ellekjær, Hanne, Skovlund, Eva
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.08.2019; Public Library of Science (PLoS)
• Subjects: Aged; Aging; Analysis; Anticoagulants; Apixaban; Atrial fibrillation; Atrial Fibrillation - drug therapy; Atrial Fibrillation - epidemiology; Bleeding; Cardiac arrhythmia; Censorship; Chronic illnesses; Dabigatran - adverse effects; Dabigatran - therapeutic use; Disease prevention; Dosage and administration; Drug therapy; Embolism; Female; Fibrillation; Follow-Up Studies; Hazards; Health hazards; Health risks; Health sciences; Humans; Identification methods; Ischemia; Male; Medicine; Medicine and Health Sciences; Patients; People and Places; Practice guidelines (Medicine); Public health; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyridones - adverse effects; Pyridones - therapeutic use; Research and Analysis Methods; Rivaroxaban; Rivaroxaban - adverse effects; Rivaroxaban - therapeutic use; Safety; Statistical analysis; Statistical models; Stroke; Studies; Transient ischemic attack; Treatment Outcome; Warfarin; Warfarin - adverse effects; Warfarin - therapeutic use; Europe; Norway
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0221500

To compare effectiveness and safety of warfarin and the direct oral anticoagulants (DOAC) dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation in routine care. From nationwide registries, we identified treatment-naïve patients initiating warfarin, dabigatran, rivaroxaban or apixaban for non-valvular atrial fibrillation from July 2013 to December 2015 in Norway. We assessed prescription duration using reverse waiting time distribution. Adjusting for confounding in a Cox proportional hazards model, we estimated one-year risks for ischemic stroke, transient ischemic attack (TIA) or systemic embolism, major or clinically relevant non-major bleeding; intracranial; gastrointestinal; and other bleeding. We censored at switch of treatment or 365 days of follow-up. We included 30,820 treatment-naïve patients. Compared to warfarin, the adjusted hazard ratios (HR) for ischemic stroke, TIA or systemic embolism were 0.96 (95% CI 0.71-1.28) for dabigatran, 1.12 (95% CI 0.87-1.45) for rivaroxaban and 0.97 (95% CI 0.75-1.26) for apixaban. Corresponding hazard ratios for major or clinically relevant non-major bleeding were 0.73 (95% CI 0.62-0.86) for dabigatran, 0.97 (95% CI 0.84-1.12) for rivaroxaban and 0.71 (95% CI 0.62-0.82) for apixaban. Statistically significant differences of other safety outcomes compared to warfarin were fewer intracranial bleedings with dabigatran (HR 0.28, 95% CI 0.14-0.56), rivaroxaban (HR 0.40, 95% CI 0.23-0.69) and apixaban (HR 0.56, 95% CI 0.34-0.92); fewer gastrointestinal bleedings with apixaban (HR 0.70, 95% CI 0.52-0.93); and fewer other bleedings with dabigatran (HR 0.67, 95% CI 0.55-0.81) and apixaban (HR 0.70, 95% CI 0.59-0.83). After 1 year follow-up in treatment-naïve patients initiating oral anticoagulation for non-valvular atrial fibrillation, all DOACs were similarly effective as warfarin in prevention of ischemic stroke, TIA or systemic embolism. Safety from bleedings was similar or better, including fewer intracranial bleedings with all direct oral anticoagulants, fewer gastrointestinal bleedings with apixaban and fewer other bleedings with dabigatran and apixaban.