title: Clinical impact and course of major bleeding with rivaroxaban and vitamin K antagonists.
abstract: BACKGROUND
  Rivaroxaban is a new oral anticoagulant (NOAC) that can be prescribed in a fixed dose, making regular monitoring and dose adjustments unnecessary. It has been proven to be safe and effective in comparison with enoxaparin/vitamin K antagonists (LMWH/VKA) for the (extended) treatment of venous thromboembolism in the EINSTEIN studies. Nevertheless, there is a need for information regarding the clinical impact of (major) bleeding events with NOACs such as rivaroxaban.
  
  
  OBJECTIVE
  A post-hoc analysis was performed to compare the severity of clinical presentation and subsequent clinical course of major bleeding with rivaroxaban vs. LMWH/VKA.
  
  
  METHODS
  Two investigators performed a blinded classification of major bleeding using a priori defined criteria. During the EINSTEIN studies, data concerning the clinical course and measures applied were prospectively collected for each major bleed.
  
  
  RESULTS
  Treatment with LMWH/VKA caused more major bleeding events (1.7%) than rivaroxaban (1.0%; hazard ratio, 0.54; 95% confidence interval [CI], 0.37-0.79). Major bleeding events during rivaroxaban therapy had a milder presentation (23% were adjudicated to the worst categories vs. 38% for LMWH/VKA; hazard ratio or HR, 0.35; 95% CI, 0.17-0.74; P = 0.0062). The clinical course was severe in 25% of all major bleeding events associated with rivaroxaban, compared with 33% of LMWH/VKA-associated bleeds (HR, 0.46; 95% CI, 0.22-0.96; P = 0.040).
  
  
  CONCLUSIONS
  Rivaroxaban-associated major bleeding events occurred less frequently, had a milder presentation and appeared to take a less severe clinical course compared with major bleeding with LMWH/VKA.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: E S
authors.initials: ES
authors.lastname: Eerenberg
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Middeldorp
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.affiliation: Bayer HealthCare, Wuppertal, Germany.
authors.forename: A W
authors.initials: AW
authors.lastname: Lensing
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D015942:Factor VIIa / Q000627:therapeutic use; D065427:Factor Xa Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology / Q000628:therapy; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D010949:Plasma; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000209:etiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D000069552:Rivaroxaban / Q000009:adverse effects* / Q000627:therapeutic use; D012720:Severity of Illness Index; D016037:Single-Blind Method; D019851:Thrombophilia / Q000188:drug therapy; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000209:etiology; D014812:Vitamin K / Q000037:antagonists & inhibitors* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D011994:Recombinant Proteins; D014812:Vitamin K; C025667:prothrombin complex concentrates; D000069552:Rivaroxaban; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: anticoagulants; coumarins; hemorrhage; rivaroxaban; venous thromboembolism