Effect of Aspirin vs Enoxaparin on 90-Day Mortality in Patients Undergoing Hip or Knee Arthroplasty: A Secondary Analysis of the CRISTAL Cluster Randomized Trial

Verinder S. Sidhu, Thu Lan Kelly, Nicole Pratt, Stephen E. Graves, Rachelle Buchbinder, Sam Adie, Kara Cashman, Ilana N. Ackerman, Durga Bastiras, Roger Brighton, Alexander W.R. Burns, Beng Hock Chong, Ornella Clavisi, Maggie Cripps, Mark Dekkers, Richard De Steiger, Michael Dixon, Andrew Ellis, Elizabeth C. Griffith, David HaleAmber Hansen, Anthony Harris, Raphael Hau, Mark Horsley, Dugal James, Omar Khorshid, Leonard Kuo, Peter L. Lewis, David Lieu, Michelle Lorimer, Samuel J. Macdessi, Peter McCombe, Catherine McDougall, Jonathan Mulford, Justine Maree Naylor, Richard S. Page, John Radovanovic, Michael Solomon, Rami Sorial, Peter Summersell, Phong Tran, William L. Walter, Steve Webb, Chris Wilson, David Wysocki, Ian A. Harris

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)


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 23458 patients from 31 hospitals were included, with 14156 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 21148 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.au Identifier: ACTRN12618001879257.

Original languageEnglish
Article numberE2317838
Number of pages11
JournalJAMA Network Open
Issue number6
Publication statusPublished - 9 Jun 2023

Cite this