Enoxaparin versus dabigatran or rivaroxaban for thromboprophylaxis after hip or knee arthroplasty: Results of separate pooled analyses of phase III multicenter randomized trials

Circ Cardiovasc Qual Outcomes. 2010 Nov;3(6):652-60. doi: 10.1161/CIRCOUTCOMES.110.957712. Epub 2010 Oct 5.

Abstract

Background: Dabigatran and rivaroxaban are novel oral anticoagulants approved for prevention of venous thromboembolism after hip or knee arthroplasty. However, information assessing clinically important efficacy and bleeding outcomes of these 2 new agents versus low-molecular-weight heparin (enoxaparin) is lacking.

Methods and results: We separately pooled efficacy and safety data from 6 phase III randomized trials (18 405 participants) comparing equivalent durations of treatment with enoxaparin (40 mg once daily [od] or 30 mg twice daily) versus dabigatran (220 mg od) or versus rivaroxaban (10 mg od) after hip or knee arthroplasty. Odds ratios (OR) for individual outcomes were calculated for each trial and were pooled using the Mantel-Haenszel method. Compared with dabigatran, enoxaparin had a similar risk of symptomatic venous thromboembolism plus all-cause mortality (0.9% versus 1.1%; OR, 0.76; 95% confidence interval [CI], 0.44 to 1.31; I²=76%) and bleeding (5.0% versus 5.6%; OR, 0.90; 95% CI, 0.71 to 1.15; I²=0%). Compared with rivaroxaban, enoxaparin had a 2-fold higher risk of symptomatic venous thromboembolism plus all-cause mortality (1.2% versus 0.6%; OR, 2.04; 95% CI, 1.32 to 3.17; P<0.001; number needed to treat, 167; I²=0%) but demonstrated a significant lower risk of bleeding (2.5% versus 3.1%; OR, 0.79; 95% CI, 0.62 to 0.99; P=0.049; number needed to harm, 167; I²=0%).

Conclusions: In patients undergoing hip or knee arthroplasty, enoxaparin and dabigatran showed similar rates of efficacy and bleeding. Enoxaparin was less effective than rivaroxaban but had a lower risk of bleeding. These results may have important implications for the choice of prophylactic agent in major joint arthroplasty.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Arthroplasty, Replacement, Hip*
  • Arthroplasty, Replacement, Knee*
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / adverse effects
  • Dabigatran
  • Enoxaparin / administration & dosage*
  • Enoxaparin / adverse effects
  • Follow-Up Studies
  • Hemorrhage / etiology
  • Humans
  • Morpholines / administration & dosage*
  • Morpholines / adverse effects
  • Postoperative Complications*
  • Prospective Studies
  • Rivaroxaban
  • Thiophenes / administration & dosage*
  • Thiophenes / adverse effects
  • Treatment Outcome
  • Venous Thromboembolism / epidemiology
  • Venous Thromboembolism / etiology*
  • Venous Thromboembolism / prevention & control*
  • Withholding Treatment
  • beta-Alanine / administration & dosage
  • beta-Alanine / adverse effects
  • beta-Alanine / analogs & derivatives*

Substances

  • Anticoagulants
  • Benzimidazoles
  • Enoxaparin
  • Morpholines
  • Thiophenes
  • beta-Alanine
  • Rivaroxaban
  • Dabigatran