Comparison of anti-inflammatory effects of rivaroxaban vs. dabigatran in patients with non-valvular atrial fibrillation (RIVAL-AF study): multicenter randomized study
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Some experimental studies have shown that direct oral anticoagulants (DOACs) have anti-inflammatory effects. However, the interval changes in inflammatory markers in patients with non-valvular atrial fibrillation (AF) who receive DOACs remain unknown. Between July 2013 and April 2014, a total of 187 AF patients randomly assigned to receive rivaroxaban (n = 91) or dabigatran (n = 96) were assessed for eligibility. The levels of the following inflammatory markers were serially evaluated: high-sensitivity C-reactive protein, pentraxin-3, interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α, monocyte chemotactic protein-1, growth and differentiation factor-15, and soluble thrombomodulin (sTM). The aim in this study was to evaluate the anti-inflammatory effects of rivaroxaban and dabigatran in patients with AF, in addition to the impact of markers on bleeding events. Finally, 117 patients (rivaroxaban: n = 55, dabigatran: n = 62) were included in the analysis at 12 months. Although the interval changes in sTM levels tended to be greater in the dabigatran group [0.3 (0–0.7) vs. 0.5 (0–1.0) FU/ml, p = 0.061], there were no significant differences in the interval changes in any inflammatory marker between 2 groups. There were no significant differences in bleeding events between 2 groups. The interval changes in sTM levels were significantly greater in patients with bleeding compared with those without [0.8 (0.5–1.3) vs. 0.4 (− 0.1–0.8) FU/ml, p = 0.017]. There were no significant differences in the interval changes in any inflammatory marker between rivaroxaban and dabigatran treatments in patients with AF. The increased levels of sTM after DOACs treatment might be related to bleeding events.
KeywordsInflammation Direct oral anticoagulation Atrial fibrillation Bleeding Thrombomodulin
The authors would like to express their gratitude to the physicians and paramedics participating in the RIVAL-AF study.
This study was financially supported by Bayer Yakuhin, Ltd., Osaka, Japan.
Compliance with ethical standards
Conflicts of interest
Dr. Tsukahara has received research grants from AstraZeneca K.K. and Daiichi-Sankyo Company, Limited and speakers’ Bureau/Honorarium from Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Inc., Eisai Co Ltd., and Daiichi-Sankyo Company, Limited. Dr. Kimura has received research grants from Sanofi K.K., Bayer Yakuhin Ltd., Kowa Pharmaceutical Co. LTD., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company, Eisai Co., Ltd. and Mitsubishi Tanabe Pharma Corporation, and honoraria from Daiichi-Sankyo Company, Bayer Yakuhin Ltd., AstraZeneca K.K., MSD K.K. Dr. Tamura has received research grants from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Tsumura, Daiichi-Sankyo Company, Novartis, Astellas Pharma, Inc., MSD K.K., Pfizer Japan Inc. Research Institute for Production Development, Takeda Pharmaceutical Company, Kyowa Hakko Kirin Co. LTD., Chugai Pharmaceutical Co. LTD., Mochida Pharmaceutical Co. LTD. and Mitsubishi Tanabe Pharma Corporation., and honoraria from Mochida Pharmaceutical Co. LTD., Pfizer Japan Inc. Research Institute for Production Development, Sumitomo Dainippon Pharma and Kyowa Hakko Kirin Co. LTD. .
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