Philip S Wells1, Martin H Prins2, Bennett Levitan3, Jan Beyer-Westendorf4, Timothy A Brighton5, Henri Bounameaux6, Alexander T Cohen7, Bruce L Davidson8, Paolo Prandoni9, Gary E Raskob10, Zhong Yuan3, Eva G Katz11, Martin Gebel12, Anthonie W A Lensing12. 1. Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, ON, Canada. Electronic address: pwells@toh.on.ca. 2. Maastricht University Medical Center, Maastricht, The Netherlands. 3. Janssen Pharmaceutical Research & Development LLC, Titusville, NJ. 4. Department of Vascular Medicine, University Hospital Carl-Gustav Carus, Dresden University of Technology, Dresden, Germany. 5. Department of Haematology, Prince of Wales Hospital, Sydney, NSW, Australia. 6. Division of Angiology and Hemostasis, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland. 7. Department of Haematological Medicine, Guys and St Thomas' Hospitals, King's College Hospital, London, England. 8. School of Medicine, University of Washington, Seattle, WA. 9. Department of Cardiovascular Sciences, University of Padua, Padua, Italy. 10. College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK. 11. Janssen Pharmaceutical Research & Development LLC, Raritan, NJ. 12. Bayer AG, Wuppertal, Germany.
Abstract
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. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00439725; URL: www.clinicaltrials.gov.
RCT Entities:
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. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00439725; URL: www.clinicaltrials.gov.
Authors: Chi Zhang; Bo Xu; Guanzhao Liang; Xianshang Zeng; Chen Yang; Fan Zhang; Zi Wan; Weiguang Yu; Deng Chen; Zhe Ge; Xinchao Zhang Journal: J Int Med Res Date: 2018-03-21 Impact factor: 1.671