Long-term Anticoagulation With Rivaroxaban for Preventing Recurrent VTE: A Benefit-Risk Analysis of EINSTEIN-Extension.
BACKGROUND
Short-term anticoagulant treatment for acute DVT or pulmonary embolism (PE) effectively reduces the risk of recurrent disease during the first 6 to 12 months of therapy. Continued anticoagulation often is not instituted because of the perception among physicians that the risk of major bleeding will outweigh the risk of new venous thrombotic episodes.


METHODS
The authors performed a benefit-risk analysis by using the randomized EINSTEIN-Extension trial, which compared continued rivaroxaban with placebo in 1,197 patients with symptomatic DVT or PE who had completed 6 to 12 months of anticoagulation and in whom physicians had equipoise with respect to the need for continued anticoagulation. One-year Kaplan-Meier rates and rate differences of recurrent VTE and major bleeding were calculated. Benefits and risks were assessed using rate differences scaled to a population size of 10,000 patients treated for 1 year.


RESULTS
Recurrent VTE occurred in eight recipients of rivaroxaban and 42 patients receiving placebo. In a population of 10,000 patients treated for 1 year, rivaroxaban treatment would have resulted in 665 (95% CI, 246-1,084) fewer recurrent VTEs than would placebo (number needed to treat = 15). Major bleeding occurred in four (0.7%) and zero patients, respectively. Rivaroxaban treatment would have resulted in 68 (95% CI, 2-134) more major bleeding events than would placebo (number needed to harm = 147). Kaplan-Meier analysis showed early recurrent VTE reduction with rivaroxaban that continued to improve throughout treatment; major bleeding increased gradually, plateauing at approximately 100 days.


CONCLUSIONS
A clinically important benefit and a favorable benefit-risk profile of continued rivaroxaban anticoagulation was observed.


BACKGROUND
ClinicalTrials.gov; No.: NCT00439725; URL: www.clinicaltrials.gov.
Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, ON, Canada. Electronic address: pwells@toh.on.ca.
Philip S
PS
Wells
Maastricht University Medical Center, Maastricht, The Netherlands.
Martin H
MH
Prins
Janssen Pharmaceutical Research & Development LLC, Titusville, NJ.
Bennett
B
Levitan
Department of Vascular Medicine, University Hospital Carl-Gustav Carus, Dresden University of Technology, Dresden, Germany.
Jan
J
Beyer-Westendorf
Department of Haematology, Prince of Wales Hospital, Sydney, NSW, Australia.
Timothy A
TA
Brighton
Division of Angiology and Hemostasis, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland.
Henri
H
Bounameaux
Department of Haematological Medicine, Guys and St Thomas' Hospitals, King's College Hospital, London, England.
Alexander T
AT
Cohen
School of Medicine, University of Washington, Seattle, WA.
Bruce L
BL
Davidson
Department of Cardiovascular Sciences, University of Padua, Padua, Italy.
Paolo
P
Prandoni
College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Gary E
GE
Raskob
Janssen Pharmaceutical Research & Development LLC, Titusville, NJ.
Zhong
Z
Yuan
Janssen Pharmaceutical Research & Development LLC, Raritan, NJ.
Eva G
EG
Katz
Bayer AG, Wuppertal, Germany.
Martin
M
Gebel
Bayer AG, Wuppertal, Germany.
Anthonie W A
AWA
Lensing
D004311:Double-Blind Method; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000517:prevention & control; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D000069552:Rivaroxaban / Q000627:therapeutic use*; D055502:Secondary Prevention; D015996:Survival Rate; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000517:prevention & control*
D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban
VTE; anticoagulation; benefit-risk; rivaroxaban