title: Choosing wisely: The impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials.
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.
authors.affiliation: 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Beyer-Westendorf
authors.affiliation: Bayer HealthCare Pharmaceuticals, Wuppertal, Germany.
authors.forename: Anthonie W A
authors.initials: AW
authors.lastname: Lensing
authors.affiliation: King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital, London, UK.
authors.forename: Roopen
authors.initials: R
authors.lastname: Arya
authors.affiliation: University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Henri
authors.initials: H
authors.lastname: Bounameaux
authors.affiliation: Department of Haematology, Guy's and St Thomas' Hospitals NHS Trust, London, UK.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Cohen
authors.affiliation: Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Wells
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Middeldorp
authors.affiliation: Vascular Medicine and Haemostasis, University of Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
authors.affiliation: Academic Directorate of Respiratory Medicine, Sheffield Teaching Hospitals, Sheffield, UK.
authors.forename: Rodney
authors.initials: R
authors.lastname: Hughes
authors.affiliation: Clinic for Angiology, Cardiovascular Center, University Hospital Bern, Switzerland.
authors.forename: Nils
authors.initials: N
authors.lastname: Kucher
authors.affiliation: Bayer HealthCare Pharmaceuticals, Wuppertal, Germany.
authors.forename: Akos F
authors.initials: AF
authors.lastname: Pap
authors.affiliation: Bayer HealthCare Pharmaceuticals Inc., Parsippany, NJ, USA.
authors.forename: Mila
authors.initials: M
authors.lastname: Trajanovic
authors.affiliation: Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.affiliation: Department of Cardiovascular sciences, Vascular Medicine Unit, University of Padua, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Prandoni
authors.affiliation: Thrombosis & Atherosclerosis Research Institute and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000188:drug therapy*
chemical_list: D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D000069552:Rivaroxaban
keywords: anticoagulation; apixaban; rivaroxaban; venous thromboembolism