Journal Title
Title of Journal: Heart Vessels
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Abbravation: Heart and Vessels
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Authors: Sayaka Namba Minako YamaokaTojo Ryota Kakizaki Teruyoshi Nemoto Kazuhiro Fujiyoshi Takehiro Hashikata Lisa Kitasato Takuya Hashimoto Ryo Kameda Kentaro Meguro Takao Shimohama Taiki Tojo Junya Ako
Publish Date: 2017/02/23
Volume: 32, Issue: 8, Pages: 977-982
Abstract
In recent years direct oral anticoagulants DOACs of dabigatran rivaroxaban apixaban edoxaban which are all alternatives to warfarin have been released The use of DOACs is becoming more widespread in the clinical management of thrombotic stroke risk in patients with atrial fibrillation AF In largescale clinical trials of each drug DOACs were reported to inhibit intracranial hemorrhage stroke and death compared to warfarin Warfarin is an endogenous vitamin K antagonist therefore patients who are taking warfarin must be prohibited from taking vitamin K Vitamin K is an essential cofactor required for the ɤcarboxylation of vitamin Kdependent proteins including coagulation factors osteocalcin OC matrix Gla protein MGP and the growth arrestspecific 6 GAS6 OC is a key factor for bone matrix formation MGP is a local inhibitor of soft tissue calcification in the vessel wall GAS6 prevents the apoptosis of vascular smooth muscle cells Therefore decrease of blood vitamin K levels may cause osteoporosis vascular calcification and the inhibition of vessels angiogenesis This study aimed to evaluate the effects of changing from warfarin to rivaroxaban on bone mineral metabolism vascular calcification and vascular endothelial dysfunction We studied 21 consecutive patients with persistent or chronic AF who were treated with warfarin at least for 12 months Warfarin administration was changed to rivaroxaban 10 or 15 mg/day in all patients Osteopontin OPN bone alkaline phosphatase BAP and undercarboxylated osteocalcin ucOC were measured Pulse wave velocity PWV and augmentation index AI were also measured as atherosclerosis assessments All measurements were done before and six months after the rivaroxaban treatment There was a significant increase in serum level of BAP compared to baseline 125 ± 46 to 134 ± 41 U/L P 001 In contrast there was a significant decrease in the serum level of ucOC 95 ± 50 to 27 ± 13 ng/ml P 001 Also in the ucOC levels there was a significant negative correlation between baseline values and baseline to 6months changes in high ucOC group r = −097 P 001 The atherosclerosis and osteoporosisrelated biomarker serum level of OPN were significantly decreased compared to baseline 2683 ± 468 to 2534 ± 471 ng/ml P 001 AI and PWV were significantly decreased after 6 months of treatment with rivaroxaban 339 ± 184 to 247 ± 184 P = 004 16388 ± 2230 to 16130 ± 2501 m/s P = 003 respectively Switching to rivaroxaban from warfarin in patients with atrial fibrillation was associated with an increase of bone formation markers and a decrease of bone resorption markers and also improvements of PWV and AIDr Minako YamaokaTojo was partly supported by grants from Bayer Pharma DaiichiSankyo and Boehringer Ingelheim Dr Junya Ako received speaking honorarium from Tanabe Mitsubishi DaiichiSankyo MSD KK Boehringer Ingelheim Kowa and Kyowa Hakko Kirin Other authors have nothing to disclose regarding this manuscript
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