Effect of Aspirin vs Enoxaparin on 90-Day Mortality in Patients Undergoing Hip or Knee Arthroplasty
Authors:   The CRISTAL Study Group, Sidhu Verinder S. , Kelly Thu-Lan , Pratt Nicole , Graves Stephen E. , Buchbinder Rachelle , Adie Sam , Cashman Kara , Ackerman Ilana N. , Bastiras Durga , Brighton Roger , Burns Alexander W. R. , Chong Beng Hock , Clavisi Ornella , Cripps Maggie , Dekkers Mark , de Steiger Richard , Dixon Michael , Ellis Andrew , Griffith Elizabeth C. , Hale David , Hansen Amber , Harris Anthony , Hau Raphael , Horsley Mark , James Dugal , Khorshid Omar , Kuo Leonard , Lewis Peter L. , Lieu David , Lorimer Michelle , MacDessi Samuel J. , McCombe Peter , McDougall Catherine , Mulford Jonathan , Naylor Justine Maree , Page Richard S. , Radovanovic John , Solomon Michael , Sorial Rami , Summersell Peter , Tran Phong , Walter William L. , Webb Steve , Wilson Chris , Wysocki David , Harris Ian A. 
Published: June 2023

Importance

Ischemic heart disease remains the leading cause of mortality following hip and knee arthroplasty. Due to its antiplatelet and cardioprotective properties, aspirin has been proposed as an agent that could reduce mortality when used as venous thromboembolism (VTE) prophylaxis following these procedures.

Objective

To compare aspirin with enoxaparin in reducing 90-day mortality for patients undergoing hip or knee arthroplasty procedures.

Design, Setting, and Participants

This study was a planned secondary analysis of the CRISTAL cluster randomized, crossover, registry-nested trial performed across 31 participating hospitals in Australia between April 20, 2019, and December 18, 2020. The aim of the CRISTAL trial was to determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE following hip or knee arthroplasty. The primary study restricted the analysis to patients undergoing total hip or knee arthroplasty for a diagnosis of osteoarthritis only. This study includes all adult patients (aged ≥18 years) undergoing any hip or knee arthroplasty procedure at participating sites during the course of the trial. Data were analyzed from June 1 to September 6, 2021.

Interventions

Hospitals were randomized to administer all patients oral aspirin (100 mg daily) or subcutaneous enoxaparin (40 mg daily) for 35 days after hip arthroplasty and 14 days after knee arthroplasty procedures.

Main Outcomes and Measures

The primary outcome was mortality within 90 days. The between-group difference in mortality was estimated using cluster summary methods.

Results

A total of 23 458 patients from 31 hospitals were included, with 14 156 patients allocated to aspirin (median [IQR] age, 69 [62-77] years; 7984 [56.4%] female) and 9302 patients allocated to enoxaparin (median [IQR] age, 70 [62-77] years; 5277 [56.7%] female). The mortality rate within 90 days of surgery was 1.67% in the aspirin group and 1.53% in the enoxaparin group (estimated difference, 0.04%; 95% CI, −0.05%-0.42%). For the subgroup of 21 148 patients with a nonfracture diagnosis, the mortality rate was 0.49% in the aspirin group and 0.41% in the enoxaparin group (estimated difference, 0.05%; 95% CI, −0.67% to 0.76%).

Conclusions and Relevance

In this secondary analysis of a cluster randomized trial comparing aspirin with enoxaparin following hip or knee arthroplasty, there was no significant between-group difference in mortality within 90 days when either drug was used for VTE prophylaxis.

Trial Registration

http://anzctr.org.auIdentifier:ACTRN12618001879257