Safety and efficacy of new oral anticoagulants and low-molecular-weight heparins compared with aspirin in patients undergoing total knee and hip replacements.
There has been much debate recently on the best type of thromboprophylaxis following elective total joint replacement surgery.



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.



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.



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.



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.
Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands. j.t.h.nielen@uu.nl.|Department of Epidemiology, CAPHRI, Maastricht University, Maastricht, The Netherlands. j.t.h.nielen@uu.nl.
Johannes T H
JT
Nielen
Department of Epidemiology, CAPHRI and CARIM, Maastricht University, Maastricht, The Netherlands.
Pieter C
PC
Dagnelie
Department of Orthopaedics, Maastricht University Medical Center +, Maastricht, The Netherlands.
Pieter J
PJ
Emans
Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center +, Maastricht, The Netherlands.
Nicole
N
Veldhorst-Janssen
Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.|Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
Arief
A
Lalmohamed
Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
Tjeerd-Pieter
TP
van Staa
Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Center +, Maastricht, The Netherlands.
Annelies E R C H
AE
Boonen
Department of Pharmacy, Sint Maartenskliniek, Nijmegen, The Netherlands.|Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.
Bart J F
BJ
van den Bemt
Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.|Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center +, Maastricht, The Netherlands.
Frank
F
de Vries
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D019644:Arthroplasty, Replacement, Hip / Q000379:methods*; D019645:Arthroplasty, Replacement, Knee / Q000379:methods*; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D054556:Venous Thromboembolism / Q000517:prevention & control
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin
GI bleeding; aspirin; epidemiology; low-molecular-weight heparins; mortality; new oral anticoagulants; pharmacoepidemiology; venous thromboembolism