Global Prospective Safety Analysis of Rivaroxaban

Global XANTUS program Investigators

doi:10.1016/j.jacc.2018.04.058

Global Prospective Safety Analysis of Rivaroxaban

Global XANTUS program Investigators

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	141-153
Number of pages	13
Journal	Journal of the American College of Cardiology
Volume	72
Issue number	2
DOIs	https://doi.org/10.1016/j.jacc.2018.04.058
Publication status	Published - 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

Keywords

XANTUS
atrial fibrillation
real-world
rivaroxaban
safety
stroke prevention

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jacc.2018.04.058

Cite this

@article{c3954380916041368c0a1f38bad9d177,

title = "Global Prospective Safety Analysis of Rivaroxaban",

abstract = "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.",

keywords = "XANTUS, atrial fibrillation, real-world, rivaroxaban, safety, stroke prevention",

author = "{Global XANTUS program Investigators} and Paulus Kirchhof and Ghazi Radaideh and Kim, {Young Hoon} and Fernando Lanas and Sylvia Haas and Pierre Amarenco and Turpie, {Alexander G.G.} and Miriam Bach and Marc Lambelet and Susanne Hess and Camm, {A. John}",

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: {\textcopyright} 2018 The Authors",

year = "2018",

month = jul,

day = "10",

doi = "10.1016/j.jacc.2018.04.058",

language = "English",

volume = "72",

pages = "141--153",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier USA",

number = "2",

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TY - JOUR

T1 - Global Prospective Safety Analysis of Rivaroxaban

AU - Global XANTUS program Investigators

AU - Kirchhof, Paulus

AU - Radaideh, Ghazi

AU - Kim, Young Hoon

AU - Lanas, Fernando

AU - Haas, Sylvia

AU - Amarenco, Pierre

AU - Turpie, Alexander G.G.

AU - Bach, Miriam

AU - Lambelet, Marc

AU - Hess, Susanne

AU - Camm, A. John

N1 - 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

PY - 2018/7/10

Y1 - 2018/7/10

N2 - 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.

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.

KW - XANTUS

KW - atrial fibrillation

KW - real-world

KW - rivaroxaban

KW - safety

KW - stroke prevention

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U2 - 10.1016/j.jacc.2018.04.058

DO - 10.1016/j.jacc.2018.04.058

M3 - Article

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SN - 0735-1097

VL - 72

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EP - 153

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 2

ER -

Global Prospective Safety Analysis of Rivaroxaban

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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