Jan Beyer-Westendorf1, Anthonie W A Lensing2, Roopen Arya3, Henri Bounameaux4, Alexander T Cohen5, Philip S Wells6, Saskia Middeldorp7, Peter Verhamme8, Rodney Hughes9, Nils Kucher10, Akos F Pap2, Mila Trajanovic11, Martin H Prins12, Paolo Prandoni13, Jeffrey I Weitz14. 1. Thrombosis Research Unit, Center for Vascular Medicine and Department of Medicine III, University Hospital "Carl Gustav Carus" Dresden, Germany. Electronic address: jan.beyer@uniklinikum-dresden.de. 2. Bayer HealthCare Pharmaceuticals, Wuppertal, Germany. 3. King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital, London, UK. 4. University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland. 5. Department of Haematology, Guy's and St Thomas' Hospitals NHS Trust, London, UK. 6. Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, Canada. 7. Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands. 8. Vascular Medicine and Haemostasis, University of Leuven, Belgium. 9. Academic Directorate of Respiratory Medicine, Sheffield Teaching Hospitals, Sheffield, UK. 10. Clinic for Angiology, Cardiovascular Center, University Hospital Bern, Switzerland. 11. Bayer HealthCare Pharmaceuticals Inc., Parsippany, NJ, USA. 12. Maastricht University Medical Center, Maastricht, Netherlands. 13. Department of Cardiovascular sciences, Vascular Medicine Unit, University of Padua, Italy. 14. Thrombosis & Atherosclerosis Research Institute and McMaster University, Hamilton, Ontario, Canada.
Abstract
BACKGROUND: The results of the EINSTEIN-DVT/PE and AMPLIFY trials, which compared rivaroxaban and apixaban with conventional anticoagulation therapy for acute venous thromboembolism (VTE), respectively, are often compared. However, the trials differed in duration of therapy (3-12 and 6months, respectively) and in patient selection (few exclusion criteria and more stringent exclusion criteria, respectively). METHODS: To determine the effect of these methodological differences on outcomes, the patients enrolled in EINSTEIN-DVT/PE were divided into 2 cohorts; the 5253 patients that matched the exclusion criteria for AMPLIFY and were treated for at least 6months (cohort 1) and the 2368 patients who would have been ineligible for AMPLIFY (cohort 2). RESULTS: Compared with patients in cohort 2, those in cohort 1 were older and more often male and there were more with unprovoked VTE, prior VTE, cancer and known thrombophilia. In cohort 1, rivaroxaban would have significantly reduced recurrent VTE (relative risk [RR], 0.64; 95% confidence interval [CI], 0.43-0.95) and major bleeding (RR, 0.50; 95% CI, 0.30-0.82) compared with conventional therapy, whereas the two treatments would have had similar effects on recurrent VTE (RR, 1.08; 95% CI, 0.65-1.79) and major bleeding (RR, 1.03; 95% CI, 0.48-2.18) in cohort 2. CONCLUSIONS: This analysis illustrates the influence of patient selection and treatments duration on outcome results and highlights the limitations of cross-trial comparisons.
BACKGROUND: The results of the EINSTEIN-DVT/PE and AMPLIFY trials, which compared rivaroxaban and apixaban with conventional anticoagulation therapy for acute venous thromboembolism (VTE), respectively, are often compared. However, the trials differed in duration of therapy (3-12 and 6months, respectively) and in patient selection (few exclusion criteria and more stringent exclusion criteria, respectively). METHODS: To determine the effect of these methodological differences on outcomes, the patients enrolled in EINSTEIN-DVT/PE were divided into 2 cohorts; the 5253 patients that matched the exclusion criteria for AMPLIFY and were treated for at least 6months (cohort 1) and the 2368 patients who would have been ineligible for AMPLIFY (cohort 2). RESULTS: Compared with patients in cohort 2, those in cohort 1 were older and more often male and there were more with unprovoked VTE, prior VTE, cancer and known thrombophilia. In cohort 1, rivaroxaban would have significantly reduced recurrent VTE (relative risk [RR], 0.64; 95% confidence interval [CI], 0.43-0.95) and major bleeding (RR, 0.50; 95% CI, 0.30-0.82) compared with conventional therapy, whereas the two treatments would have had similar effects on recurrent VTE (RR, 1.08; 95% CI, 0.65-1.79) and major bleeding (RR, 1.03; 95% CI, 0.48-2.18) in cohort 2. CONCLUSIONS: This analysis illustrates the influence of patient selection and treatments duration on outcome results and highlights the limitations of cross-trial comparisons.