Global Prospective Safety Analysis of Rivaroxaban

Global XANTUS program Investigators

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    42 Citations (Scopus)


    Background: The efficacy of direct oral anticoagulants (DOACs) for stroke prevention in patients with atrial fibrillation (AF) has been established in clinical trials. However, well-conducted, prospective, real-world observational studies of the safety and effectiveness of DOACs are needed. Objectives: This study sought to assess the real-world safety profile of rivaroxaban through a pooled analysis of patients with AF enrolled in the XANTUS (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation) program worldwide. Methods: A pre-planned pooled analysis of the XANTUS, XANAP (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Asia), and XANTUS-EL (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Latin America and EMEA Region) registries was performed. Patients with AF newly starting rivaroxaban for stroke prevention were followed for 1 year. Primary outcomes were treatment-emergent major bleeding, adverse events (AEs)/serious AEs, and all-cause death. Secondary outcomes included treatment-emergent thromboembolic events and nonmajor bleeding. Major outcomes were centrally adjudicated. Results: Overall, 11,121 patients were included (mean age 70.5 ± 10.5 years; female 42.9%). Comorbidities included heart failure (21.2%), hypertension (76.2%), and diabetes (22.3%). Event rates were: events/100 patient-years: major bleeding 1.7 (95% confidence interval [CI]: 1.5 to 2.0; lowest: Latin America 0.7; highest: Western Europe, Canada, and Israel 2.3); all-cause death 1.9 (95% CI: 1.6 to 2.2; lowest: Eastern Europe 1.5; highest: Latin America, Middle East, and Africa 2.7); and stroke or systemic embolism 1.0 (95% CI: 0.8 to 1.2; lowest: Latin America 0; highest: East Asia 1.8). One-year treatment persistence was 77.4% (lowest: East Asia 66.4%; highest: Eastern Europe 84.4%). Conclusions: This large, prospective, real-world analysis in 11,121 patients from 47 countries showed low bleeding and stroke rates in rivaroxaban-treated patients with AF, with low treatment discontinuation in different regions of the world. Results were broadly consistent across regions.

    Original languageEnglish
    Pages (from-to)141-153
    Number of pages13
    JournalJournal of the American College of Cardiology
    Issue number2
    Publication statusPublished - 2018 Jul 10

    Bibliographical note

    Funding Information:
    The XANTUS research programme was funded by Bayer. Dr. Kirchhof has received research support from the European Union, the British Heart Foundation, the Leducq Foundation, the Medical Research Council (U.K.), the German Centre for Cardiovascular Research, 3M Medica, MEDA Pharma, AstraZeneca, Bayer HealthCare, Biosense Webster, Boehringer Ingelheim, Daiichi-Sankyo, German Cardiac Society, Medtronic, Merck Sharp & Dohme, Otsuka Pharma, Pfizer/Bristol-Myers Squibb, Sanofi, Servier, Siemens, and Takeda; has received honoraria from several such companies; and is listed as an inventor on 2 pending patents held by the University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). Dr. Radaideh has received consulting fees and honoraria from Bayer, Sanofi, Merck Sharp & Dohme, Takeda, and Servier. Dr. Lanas has been a consultant for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer. Dr. Haas has been a consultant for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer, and Sanofi. Dr. Amarenco has been a consultant for Boehringer Ingelheim, Edwards, GlaxoSmithKline, Lundbeck, Medtronic, Merck, ShingPoon, and Kowa Pharmaceutical; has served as an executive committee member for AstraZeneca, Bayer, and Pfizer: has served on the Data Safety Monitoring Board for Fibrogen; has served on the advisory boards for Bristol-Myers Squibb and Daiichi-Sankyo; and has received grants from AstraZeneca, Bristol-Myers Squibb, Boston Scientific, Pfizer, and Sanofi. Dr. Turpie has been a consultant for Bayer, Janssen Pharmaceutical Research & Development, and Portola. Drs. Bach and Hess are employees of Bayer AG. Dr. Bach holds stock in Bayer AG. Mr. Lambelet is an employee of Chrestos Concept, which received funding for this analysis from Bayer AG. Dr. Camm has been a consultant for Aryx, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Johnson & Johnson, Pfizer, and Sanofi; and has received grants from Bayer, Boehringer Ingelheim, and Daiichi-Sankyo. Dr. Kim has reported that he has no relationships relevant to the contents of this paper to disclose.

    Publisher Copyright:
    © 2018 The Authors


    • XANTUS
    • atrial fibrillation
    • real-world
    • rivaroxaban
    • safety
    • stroke prevention

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine


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