Observational study of dabigatran etexilate 150mg in patients with moderate renal impairment undergoing elective total hip or knee replacement

Thromb Res. 2016 Jul;143:103-10. doi: 10.1016/j.thromres.2016.05.014. Epub 2016 May 14.

Abstract

Introduction: 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.

Materials and 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.

Keywords: Anticoagulants; Bleeding; Dabigatran etexilate; Thrombosis prophylaxis; Venous thromboembolism.

Publication types

  • Clinical Trial
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antithrombins / administration & dosage
  • Antithrombins / adverse effects
  • Antithrombins / therapeutic use*
  • Arthroplasty, Replacement, Hip / adverse effects*
  • Arthroplasty, Replacement, Knee / adverse effects*
  • Dabigatran / administration & dosage
  • Dabigatran / adverse effects
  • Dabigatran / therapeutic use*
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Renal Insufficiency / complications*
  • Treatment Outcome
  • Venous Thromboembolism / complications
  • Venous Thromboembolism / etiology*
  • Venous Thromboembolism / prevention & control*

Substances

  • Antithrombins
  • Dabigatran