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Clinical Trial
. 2017 Oct 1;74(10):1206-1215.
doi: 10.1001/jamaneurol.2017.2161.

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation-Related Mild Ischemic Stroke: A Randomized Clinical Trial

Keun-Sik Hong  1 , Sun U Kwon  2 , Sang Hun Lee  3 , Ji Sung Lee  4 , Yong-Jae Kim  5 , Tae-Jin Song  5 , Young Dae Kim  6 , Man-Seok Park  7 , Eung-Gyu Kim  8 , Jae-Kwan Cha  9 , Sang Min Sung  10 , Byung-Woo Yoon  11 , Oh Young Bang  12 , Woo-Keun Seo  12 , Yang-Ha Hwang  13 , Seong Hwan Ahn  14 , Dong-Wha Kang  2 , Hyun Goo Kang  14 , Kyung-Ho Yu  15 ; Phase 2 Exploratory Clinical Study to Assess the Effects of Xarelto (Rivaroxaban) Versus Warfarin on Ischemia, Bleeding, and Hospital Stay in Acute Cerebral Infarction Patients With Non-valvular Atrial Fibrillation (Triple AXEL) Study Group
Affiliations
Clinical Trial

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation-Related Mild Ischemic Stroke: A Randomized Clinical Trial

Keun-Sik Hong et al. JAMA Neurol. .

Abstract

Importance: In atrial fibrillation (AF)-related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear.

Objective: To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke.

Design, setting, and participants: A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis.

Interventions: Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks.

Main outcomes and measures: The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length.

Results: Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001).

Conclusions and relevance: In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy.

Trial registration: clinicaltrials.gov Identifier: NCT02042534.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hong reported receiving grants from Bayer Korea Ltd during the conduct of the study; grants from Boehringer Ingelheim, Bayer, and Ostuka Korea; grants and personal fees from Pfizer Korea, Bayer Korea, and Boehringer Ingelheim Korea; and personal fees from Sanofi Korea, Chong Kun Dang Pharm, Dong Wha Pharm, United Pharm, and Daichi Sankyo Korea outside the submitted work. Dr Kwon reported receiving grants from Bayer Korea Ltd and Korean Health Technology R&D Project (Ministry of Health & Welfare, Republic of Korea [HI14C1061 and HI10C2020]) during the conduct of the study; grants from Pfizer and Boehringer Ingelheim; grants and personal fees from Otsuka Korea; and personal fees from AstraZeneca Korea, Bayer Korea, Novartis Korea, Pfizer Korea, and Daichi Sankyo Korea outside the submitted work. Drs J. S. Lee, Y.-J. Kim, Song, Y. D. Kim, Park, E.-G. Kim, Bang, and Ahn reported receiving grants from Bayer Korea Ltd during the conduct of the study. Dr Cha reported receiving grants from Bayer Korea Ltd during the conduct of the study; grants from Otsuka Korea, Bayer Korea, ESAI-Korea, Daewoong Pharmaceutical Co Ltd, Daichi Sankyo, Pfizer, Sanofi Korea, and AstraZeneca Korea; and personal fees from Bayer Korea, Boehringer Ingelheim Korea, Pfizer Korea, AstraZeneca Korea, Bayer Korea, Novartis Korea, Otsuka Korea, Pfizer Korea, and Daichi Sankyo Korea outside the submitted work. Dr Sung reported receiving grants from Bayer Korea Ltd during the conduct of the study and personal fees from Daiichi Sankyo Korea and Pfizer Pharmaceuticals Korea Ltd outside the submitted work. Dr Yoon reported receiving grants from Bayer Korea Ltd during the conduct of the study and grants from Bayer HealthCare outside the submitted work. Dr Seo reported receiving grants from Bayer Korea Ltd during the conduct of the study; grants from Korea Otsuka, Daewoong Pharmaceutical Co Ltd, Myung In Pharmaceutical Co Ltd, and Korea United Pharm Inc; grants and personal fees from Bayer Korea, Pfizer Pharmaceuticals, Sanofi Korea, and Boehringer Ingelheim Korea; and personal fees from Daiichi Sankyo Korea outside the submitted work. Dr Hwang reported receiving grants from Bayer Korea Ltd during the conduct of the study and grants from Kyungpook National University outside the submitted work. Dr D.-W. Kang reported receiving grants from National Research Foundation of Korea funded by the Korea government (NRF-2014R1A2A1A11051280) and Korea Health Technology R&D Project (Ministry for Health & Welfare, Republic of Korea [HI12C1847 and HI14C1983]) outside the submitted work. Dr K.-H. Yu reported receiving grants from Bayer Korea Ltd during the conduct of the study and personal fees from Bristol-Myers Squibb and Bayer outside the submitted work. No other conflicts were reported.

Figures

Figure.
Figure.. Study Flowchart
MRI indicates magnetic resonance imaging.
See this image and copyright information in PMC

Comment in

References

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