PMID- 29976287 OWN - NLM STAT- MEDLINE DCOM- 20190819 LR - 20190819 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 72 IP - 2 DP - 2018 Jul 10 TI - Global Prospective Safety Analysis of Rivaroxaban. PG - 141-153 LID - S0735-1097(18)34795-8 [pii] LID - 10.1016/j.jacc.2018.04.058 [doi] AB - 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. (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation [XANTUS]; NCT01606995; Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Latin America and EMEA Region [XANTUS-EL]; NCT01800006; and Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Asia [XANAP]; NCT01750788). CI - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Kirchhof, Paulus AU - Kirchhof P AD - Institute of Cardiovascular Sciences, University of Birmingham, UHB and Sandwell & West Birmingham Hospitals NHS Trusts, Birmingham, United Kingdom. Electronic address: P.Kirchhof@bham.ac.uk. FAU - Radaideh, Ghazi AU - Radaideh G AD - Department of Cardiology, Rashid Hospital of Dubai, Dubai, United Arab Emirates. FAU - Kim, Young-Hoon AU - Kim YH AD - Division of Cardiology, Department of Internal Medicine, Korea University Medical Centre, Seoul, South Korea. FAU - Lanas, Fernando AU - Lanas F AD - Hospital Dr. Hernan Henriquez Aravena, Universidad de La Frontera, Temuco, Chile. FAU - Haas, Sylvia AU - Haas S AD - Formerly Klinikum rechts der Isar, Technical University Munich, Munich, Germany. FAU - Amarenco, Pierre AU - Amarenco P AD - Department of Neurology and Stroke Centre, Paris-Diderot-Sorbonne University, Paris, France. FAU - Turpie, Alexander G G AU - Turpie AGG AD - Department of Medicine, McMaster University, Hamilton, Ontario, Canada. FAU - Bach, Miriam AU - Bach M AD - Medical Affairs, Bayer AG, Berlin, Germany. FAU - Lambelet, Marc AU - Lambelet M AD - Chrestos Concept GmbH & Co KG, Essen, Germany. FAU - Hess, Susanne AU - Hess S AD - Medical Affairs, Bayer AG, Berlin, Germany. FAU - Camm, A John AU - Camm AJ AD - Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, United Kingdom; Department of Genetics and Imaging, Faculty of Medicine, Imperial College London, London, United Kingdom. CN - Global XANTUS program Investigators LA - eng SI - ClinicalTrials.gov/NCT01606995 SI - ClinicalTrials.gov/NCT01800006 SI - ClinicalTrials.gov/NCT01750788 PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Factor Xa Inhibitors) RN - 9NDF7JZ4M3 (Rivaroxaban) CIN - J Am Coll Cardiol. 2018 Jul 10;72(2):154-155. PMID: 29976288 CIN - J Am Coll Cardiol. 2018 Nov 13;72(20):2545-2546. PMID: 30442302 CIN - J Am Coll Cardiol. 2018 Nov 13;72(20):2546-2547. PMID: 30442303 MH - Aged MH - Aged, 80 and over MH - Atrial Fibrillation/*complications MH - Factor Xa Inhibitors/*adverse effects MH - Female MH - Hemorrhage/*chemically induced MH - Humans MH - Male MH - Middle Aged MH - Prospective Studies MH - Rivaroxaban/*adverse effects MH - Stroke/etiology/*prevention & control OTO - NOTNLM OT - XANTUS OT - atrial fibrillation OT - real-world OT - rivaroxaban OT - safety OT - stroke prevention EDAT- 2018/07/07 06:00 MHDA- 2019/08/20 06:00 CRDT- 2018/07/07 06:00 PHST- 2017/11/20 00:00 [received] PHST- 2018/04/10 00:00 [revised] PHST- 2018/04/12 00:00 [accepted] PHST- 2018/07/07 06:00 [entrez] PHST- 2018/07/07 06:00 [pubmed] PHST- 2019/08/20 06:00 [medline] AID - S0735-1097(18)34795-8 [pii] AID - 10.1016/j.jacc.2018.04.058 [doi] PST - ppublish SO - J Am Coll Cardiol. 2018 Jul 10;72(2):141-153. doi: 10.1016/j.jacc.2018.04.058.