Safety and efficacy of new oral anticoagulants and low-molecular-weight heparins compared with aspirin in patients undergoing total knee and hip replacements

Pharmacoepidemiol Drug Saf. 2016 Nov;25(11):1245-1252. doi: 10.1002/pds.4089. Epub 2016 Sep 4.

Abstract

Background: There has been much debate recently on the best type of thromboprophylaxis following elective total joint replacement surgery.

Objective: This study aims to compare rates of venous thromboembolism (VTE), gastro-intestinal (GI) bleeding and mortality events, with use of new oral anticoagulants (NOAC) or low-molecular-weight heparins (LMWHs) compared with aspirin in patients undergoing total joint replacement.

Methods: A population-based retrospective cohort study was performed using the Clinical Practice Research Datalink. Patients ≥18 years of age who had undergone total knee (n = 3261) or hip replacement (THR (n = 4016)) between 2008 and 2012 were included. Within this population, three cohorts were selected, based on their first prescription within the 35-day period after surgery: use of NOACs only, LMWHs only and aspirin only. Incidence rates were calculated, and Cox proportional hazard models were fitted to estimate the risk of VTE, GI bleeding and all-cause mortality with the use of NOACs and LMWHs compared with aspirin use after total knee replacement and THR. We statistically adjusted our analyses for lifestyle factors, comorbidities and concomitant drug use.

Results: Total knee replacement and THR patients currently on LMWHs had higher risk of VTE (HR = 17.2 (6.9-43.0) and HR = 39.5 (18.0-87.0), respectively), GI bleeding (HR = 20.9 (1.9-232.3) and HR = 2.0 (0.2-17.2), respectively) and all-cause mortality (HR = 4.3 (1.7-12.4) and HR = 4.0 (2.4-6.7), respectively). NOAC use was associated with an increased risk of GI bleeding in patients undergoing THR surgery.

Conclusions: In contrast to previous studies, we found an increased risk of VTE, GI bleeding and all-cause mortality with the use of LMWHs compared with aspirin. Risk of GI bleeding was increased with the use of NOACs compared with aspirin use after THR surgery. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: GI bleeding; aspirin; epidemiology; low-molecular-weight heparins; mortality; new oral anticoagulants; pharmacoepidemiology; venous thromboembolism.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Arthroplasty, Replacement, Hip / methods*
  • Arthroplasty, Replacement, Knee / methods*
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / epidemiology
  • Heparin, Low-Molecular-Weight / administration & dosage
  • Heparin, Low-Molecular-Weight / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk
  • Venous Thromboembolism / prevention & control

Substances

  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Platelet Aggregation Inhibitors
  • Aspirin