Yuka Hitaka1, Masahiro Ogawa2, Bo Zhang3, Shunichiro Goto4, Yoshihisa Nagata5, Joji Morii4, Satoshi Imaizumi4, Tomoo Yasuda4, Naomichi Matsumoto1, Akira Matsunaga6, Keijiro Saku5. 1. Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan; Department of Clinical Laboratory, Fukuoka University School of Medicine, Fukuoka, Japan. 2. Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan; Endowed Department of Advanced Therapeutics for Cardiovascular Disease, Fukuoka University School of Medicine, Fukuoka, Japan. Electronic address: ogawa0376@gmail.com. 3. Department of Biochemistry, Fukuoka University School of Medicine, Fukuoka, Japan. 4. Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan. 5. Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan; Endowed Department of Advanced Therapeutics for Cardiovascular Disease, Fukuoka University School of Medicine, Fukuoka, Japan. 6. Department of Clinical Laboratory, Fukuoka University School of Medicine, Fukuoka, Japan.
Abstract
BACKGROUND: Although rivaroxaban has a relatively shorter half-life and peak and trough plasma concentrations throughout the day than warfarin, rivaroxaban has been found to be non-inferior to warfarin in preventing thromboembolic events in patients with nonvalvular atrial fibrillation (NVAF). We measured circadian variations in laboratory measurements of coagulation assays for chronic treatment with rivaroxaban or warfarin in patients with NVAF. METHODS: We included 28 consecutive patients with NVAF who were treated with rivaroxaban (n=13) or warfarin (n=15). Blood samples were collected at 6 AM, 11 AM, and 3 PM on the same day and on the next morning at 6 AM. Prothrombin time (PT), international normalized ratio of the PT (PT-INR), activated partial thromboplastin time (APTT), prothrombin fragment 1+2 (F1+2), and protein C level/activity were measured in each patient. RESULTS: PT and PT-INR were significantly and consistently lower, and the F1+2 and protein C level/activity were significantly and consistently higher throughout the day in rivaroxaban-treated patients than in warfarin-treated patients. Significant increases in PT and PT-INR were observed 3h after oral administration in the patients taking rivaroxaban in the morning, whereas, significant increases in the protein C level/activity were observed 3h after oral administration in the patients taking warfarin in the morning. CONCLUSIONS: The protein C level/activity was significantly and consistently higher in the rivaroxaban-treated patients than in the warfarin-treated patients throughout the day, which was in contrast to the findings for other coagulation assays. These findings may partly explain the specific persistent anticoagulant effects of rivaroxaban even during the trough phase of the plasma concentration.
BACKGROUND: Although rivaroxaban has a relatively shorter half-life and peak and trough plasma concentrations throughout the day than warfarin, rivaroxaban has been found to be non-inferior to warfarin in preventing thromboembolic events in patients with nonvalvular atrial fibrillation (NVAF). We measured circadian variations in laboratory measurements of coagulation assays for chronic treatment with rivaroxaban or warfarin in patients with NVAF. METHODS: We included 28 consecutive patients with NVAF who were treated with rivaroxaban (n=13) or warfarin (n=15). Blood samples were collected at 6 AM, 11 AM, and 3 PM on the same day and on the next morning at 6 AM. Prothrombin time (PT), international normalized ratio of the PT (PT-INR), activated partial thromboplastin time (APTT), prothrombin fragment 1+2 (F1+2), and protein C level/activity were measured in each patient. RESULTS: PT and PT-INR were significantly and consistently lower, and the F1+2 and protein C level/activity were significantly and consistently higher throughout the day in rivaroxaban-treated patients than in warfarin-treated patients. Significant increases in PT and PT-INR were observed 3h after oral administration in the patients taking rivaroxaban in the morning, whereas, significant increases in the protein C level/activity were observed 3h after oral administration in the patients taking warfarin in the morning. CONCLUSIONS: The protein C level/activity was significantly and consistently higher in the rivaroxaban-treated patients than in the warfarin-treated patients throughout the day, which was in contrast to the findings for other coagulation assays. These findings may partly explain the specific persistent anticoagulant effects of rivaroxaban even during the trough phase of the plasma concentration.