Enoxaparin, Aspirin Similar for VTE Prevention in Patients Undergoing Hip or Knee Arthroplasty

Enoxaparin and aspirin as VTE prophylaxis are similarly effective for prevention of mortality among patients undergoing hip or knee arthroplasty.

Enoxaparin and aspirin show comparable effectiveness for preventing mortality when used as prophylaxis against venous thromboembolism (VTE) following hip or knee arthroplasty, according to research published in JAMA Network Open.

Orthopedic joint procedures such as total hip arthroplasty (THA) and total knee arthroplasty (TKA) carry considerable postoperative complications, with VTE being one of the most common. Postoperative prophylaxis often consists of direct oral anticoagulants (DOAC) or low-molecular-weight heparin. With ischemic heart disease being the leading cause of death within 90 days following the procedure, researchers compared postoperative mortality rates among patients undergoing hip or knee arthroplasty receiving either aspirin or enoxaparin monotherapy.

A secondary analysis was conducted using the CRISTAL trial, a randomized crossover trial that compared aspirin with enoxaparin for VTE prophylaxis in hip or knee arthroplasty. The trial consisted of adult patients who underwent arthroplasty procedures at 31 hospitals between April 15, 2019, and December 18, 2020. Patients received daily doses of either aspirin 100 mg or enoxaparin 40 mg within 24 hours of the procedure. Treatment was administered for 35 days among patients undergoing hip arthroplasty and 14 days among those undergoing knee arthroplasty.

The primary outcome of interest was all-cause mortality within 90 days of the procedure.

These findings suggest that enoxaparin reduces the risk of symptomatic VTE without increasing the risk of mortality in comparison to aspirin after hip or knee arthroplasty.

A total of 23,458 patients were included in the study, of whom 14,156 received aspirin and 9302 received enoxaparin. Patient demographics were similar between both groups.

Mortality within 90 days occurred in 236 patients (1.67%) in the aspirin group and 142 patients (1.53%) in the enoxaparin group; no statistically significant difference was found between both groups (estimated difference, 0.04%; 95% CI, -0.38% to 0.46%).

A subgroup analysis for all-cause 90-day postoperative mortality based on diagnostic indication (fracture vs no fracture) revealed no significant difference between subgroups. Mortality within 90 days for a nonfracture diagnosis occurred in 0.49% and 0.41% of patients receiving enoxaparin and aspirin, respectively (estimated difference, 0.05%; 95% CI, -0.67% to 0.76%). For a fracture diagnosis, 90-day mortality was 13.1% for the aspirin group and 11.0% for the enoxaparin group (estimated difference, 1.0%; 95% CI -1.0% to 3.0%).

The causes of death within both groups were unknown, potentially limiting available information on the extent VTE prophylaxis contributes to mortality. Additionally, some patients may have received other forms of anticoagulation (DOAC, warfarin, or dual antiplatelet medications), leading to a possible confounding effect.

The study authors concluded, “[T]hese findings suggest that enoxaparin reduces the risk of symptomatic VTE without increasing the risk of mortality in comparison to aspirin after hip or knee arthroplasty.”

Disclosure: One study author declared affiliations with industry. Please see the reference for a full list of disclosures.


Sidhu VS, Kelly T, Pratt N, et al. 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. JAMA Netw Open. 2022;328(8):719-727. doi:10.1001/jamanetworkopen.2023.17838