title: Observational study of dabigatran etexilate 150mg in patients with moderate renal impairment undergoing elective total hip or knee replacement.
abstract: BACKGROUND
  The standard dabigatran etexilate dosage for prevention of venous thromboembolism (VTE) after elective total hip or knee replacement (THR/TKR) is 220mg once daily (qd), with 150mg qd for patients with moderate renal impairment. As clinical trial experience in patients with moderate renal impairment was limited at the time of approval, we conducted an observational study to evaluate the 150mg qd dose.
  
  
  METHODS
  This open-label, prospective, uncontrolled, observational study in patients with creatinine clearance (CrCl) 30-50mL/min was conducted in seven European countries. Patients received 75mg dabigatran etexilate 1-4h after surgery and 150mg qd on days 2-10 (TKR) or 2-35 (THR), per the European Summary of Product Characteristics. Coprimary outcomes were major bleeding events (MBEs) and a composite of symptomatic VTE and all-cause mortality.
  
  
  RESULTS
  428 renally impaired patients with median CrCl 43.4mL/min (range 30.0-49.9), and median age 80years (range 32-96) received dabigatran etexilate: median treatment duration THR 31days, TKR 28days. Ten MBEs occurred in nine patients (2.1%; 95% confidence interval [CI]: 1.0-4.0; THR 1.8%; TKR 2.4%); none were fatal or involved a critical organ. Symptomatic VTE and all-cause mortality occurred in three patients (0.7%; 95% CI: 0.1-2.0; THR 0.9%; TKR 0.5%). Overall, 54 patients discontinued treatment prematurely, including 35 due to an adverse event (nine bleeding-related) and 16 switching to another anticoagulant.
  
  
  CONCLUSIONS
  Dabigatran etexilate 150mg qd had a good safety profile and was efficacious in fragile, elderly, renally impaired patients undergoing THR or TKR. These findings from the clinical practice setting add to the existing clinical trial data.
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Hôtel Dieu and Cochin University Hospitals, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France. Electronic address: marc.samama@aphp.fr.
authors.forename: Charles-Marc
authors.initials: CM
authors.lastname: Samama
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Hôtel Dieu and Cochin University Hospitals, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France. Electronic address: nadia.rosencher@aphp.fr.
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosencher
authors.affiliation: Boehringer Ingelheim GmbH & Co. KG, Ingelheim am Rhein, Germany. Electronic address: eva.kleine@boehringer-ingelheim.com.
authors.forename: Eva
authors.initials: E
authors.lastname: Kleine
authors.affiliation: Boehringer Ingelheim GmbH & Co. KG, Ingelheim am Rhein, Germany; Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. Electronic address: martin.feuring@boehringer-ingelheim.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Feuring
authors.affiliation: Boehringer Ingelheim GmbH & Co. KG, Ingelheim am Rhein, Germany; Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. Electronic address: martina.brueckman@boehringer-ingelheim.com.
authors.forename: Martina
authors.initials: M
authors.lastname: Brueckmann
authors.affiliation: Boehringer Ingelheim GmbH & Co. KG, Ingelheim am Rhein, Germany; Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany. Electronic address: andreas.clemens66@gmail.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: Clemens
authors.affiliation: Boehringer Ingelheim AB, Stockholm, Sweden. Electronic address: jenny.gullberg@boehringer-ingelheim.com.
authors.forename: Jenny
authors.initials: J
authors.lastname: Gullberg
authors.affiliation: Musculoskeletal Science Research Group, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: s.p.frostick@liverpool.ac.uk.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Frostick
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D000069604:Dabigatran / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced; D051437:Renal Insufficiency / Q000150:complications; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000150:complications / Q000209:etiology / Q000517:prevention & control
chemical_list: D000991:Antithrombins; D000069604:Dabigatran
keywords: Anticoagulants; Bleeding; Dabigatran etexilate; Thrombosis prophylaxis; Venous thromboembolism