Target International Normalized Ratio Values for Preventing Thromboembolic and Hemorrhagic Events in Japanese Patients With Non-Valvular Atrial Fibrillation: Results of the J-RHYTHM Registry

• Published in: Circulation Journal 2013, Vol.77(9), pp.2264-2270
• Main Authors: Inoue, Hiroshi, Okumura, Ken, Atarashi, Hirotsugu, Yamashita, Takeshi, Origasa, Hideki, Kumagai, Naoko, Sakurai, Masayuki, Kawamura, Yuichiro, Kubota, Isao, Matsumoto, Kazuo, Kaneko, Yoshiaki, Ogawa, Satoshi, Aizawa, Yoshifusa, Chinushi, Masaomi, Kodama, Itsuo, Watanabe, Eiichi, Koretsune, Yukihiro, Okuyama, Yuji, Shimizu, Akihiko, Igawa, Osamu, Bando, Shigenobu, Fukatani, Masahiko, Saikawa, Tetsunori, Chishaki, Akiko, on behalf of the J-RHYTHM Registry Investigators
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Asian Continental Ancestry Group; Atrial fibrillation; Atrial Fibrillation - drug therapy; Atrial Fibrillation - epidemiology; Female; Follow-Up Studies; Hemorrhage; Hemorrhage - chemically induced; Hemorrhage - epidemiology; Humans; International Normalized Ratio; Japan - epidemiology; Male; Middle Aged; Thromboembolism; Thromboembolism - epidemiology; Thromboembolism - etiology; Thromboembolism - prevention & control; Warfarin; Warfarin - administration & dosage; Warfarin - adverse effects
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.CJ-13-0290

Background: Target anticoagulation levels for warfarin in Japanese patients with non-valvular atrial fibrillation (NVAF) are unclear. Methods and Results: Of 7,527 patients with NVAF, 1,002 did not receive warfarin (non-warfarin group), and the remaining patients receiving warfarin were divided into 5 groups based on their baseline international normalized ratio (INR) of prothrombin time (≤1.59, 1.6–1.99, 2.0–2.59, 2.6–2.99, and ≥3.0). Patients were followed-up prospectively for 2 years. Primary endpoints were thromboembolic events (cerebral infarction, transient ischemic attack, and systemic embolism), and major hemorrhage requiring hospital admission. During the follow-up period, thromboembolic events occurred in 3.0% of non-warfarin group, but at lower frequencies in the warfarin groups (2.0, 1.3, 1.5, 0.6, and 1.8%/2 years for INR values of ≤1.59, 1.6–1.99, 2.0–2.59, 2.6–2.99, and ≥3.0, respectively; P=0.0059). Major hemorrhage occurred more frequently in warfarin groups (1.5, 1.8, 2.4, 3.3, and 4.1% for INR values ≤1.59, 1.6–1.99, 2.0–2.59, 2.6–2.99, and ≥3.0, respectively; P=0.0041) than in non-warfarin group (0.8%/2 years). These trends were maintained when the analyses were confined to patients aged ≥70 years. Conclusions: An INR of 1.6–2.6 is safe and effective at preventing thromboembolic events in patients with NVAF, particularly patients aged ≥70 years. An INR of 2.6–2.99 is also effective, but associated with a slightly increased risk in major hemorrhage. (UMIN Clinical Trials Registry UMIN000001569)  (Circ J 2013; 77: 2264–2270)