Dabigatran and Warfarin in Vitamin K Antagonist-Naive and -Experienced Cohorts With Atrial Fibrillation

• Published in: Circulation (New York, N.Y.) Vol. 122; no. 22; pp. 2246 - 2253
• Main Authors: EZEKOWITZ, Michael D, WALLENTIN, Lars, YUSUF, Salim, CONNOLLY, Stuart J, PAREKH, Amit, CHERNICK, Michael R, POGUE, Janice, AIKENS, Timothy H, YANG, Sean, REILLY, Paul A, LIP, Gregory Y. H
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 30-11-2010
• Subjects: Aged; anticoagulants; Anticoagulants - adverse effects; Anticoagulants - therapeutic use; arrhythmia; atrial fibrillation; Atrial Fibrillation - complications; Atrial Fibrillation - drug therapy; Benzimidazoles - adverse effects; Benzimidazoles - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Dabigatran; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dose-Response Relationship, Drug; Embolism - prevention & control; Female; Follow-Up Studies; Gastrointestinal Hemorrhage - epidemiology; Humans; Intracranial Hemorrhages - epidemiology; Male; Medical sciences; MEDICIN; MEDICINE; prevention; Pyridines - adverse effects; Pyridines - therapeutic use; Risk Factors; stroke; Stroke - prevention & control; Treatment Outcome; Vitamin K - antagonists & inhibitors; Warfarin - adverse effects; Warfarin - therapeutic use; Arrhythmia; Coumarine derivatives; Thrombin; Cardiovascular disease; Anticoagulant; Dabigatran; Antithrombin; Vascular disease; Prevention; Antivitamin K; Heart disease; Antithrombotic agent; anticoagulants; Cerebrovascular disease; Vitamin K; Nervous system diseases; Stroke; Warfarin; Serine endopeptidases; Enzyme; Atrial fibrillation; Enzyme inhibitor; Excitability disorder; Cerebral disorder; Peptidases; Central nervous system disease; Hydrolases
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.110.973735

The comparison of anticoagulants dabigatran and warfarin might be most equitable in vitamin K antagonist (VKA)-naive patients.
Warfarin and 2 doses of dabigatran-110 mg BID (D110) and 150 mg BID (D150)-were compared in a balanced population of VKA-naive (≤62 days of lifetime VKA exposure, with 33% never prescribed a VKA) and VKA-experienced patients with atrial fibrillation (n=18 113). For VKA-naive and -experienced patients assigned warfarin, the time in therapeutic range (international normalized ratio 2.0 to 3.0) was 62% and 67%, respectively, and 61% and 66% for those never and ever prescribed a VKA. In VKA-naive patients, stroke and systemic embolism rates were 1.57%, 1.07%, and 1.69% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.65); D150 was superior (P=0.005). Major bleeding rates were 3.11%, 3.34%, and 3.57% per year, respectively. D110 and D150 were similar to warfarin (P=0.19 and P=0.55). Intracranial bleeding rates were 0.19%, 0.33%, and 0.73% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 and P=0.005). In VKA-experienced patients, stroke and systemic embolism rates were 1.51%, 1.15%, and 1.74% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.32); D150 was superior (P=0.007). Major bleeding rates were 2.66%, 3.30%, and 3.57% per year, respectively. D110 was lower than warfarin (P=0.003); D150 was similar (P=0.41). Intracranial bleeding rates were 0.26%, 0.32%, and 0.79% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 for both). Results were similar for patients never on a VKA.
Previous VKA exposure does not influence the benefits of dabigatran at either dose compared with warfarin.
http://www.clinicaltrials.gov. Unique identifier: NCT00262600.