Aspirin associated with significantly higher rate of symptomatic venous thromboembolism compared to enoxaparin in patients undergoing hip or knee arthroplasty – the CRISTAL randomized trial

1. In this randomized controlled trial that included 9711 patients undergoing hip or knee arthroplasty, treatment with aspirin vs enoxaparin resulted in symptomatic VTE in 3.45% vs 1.82% of patients, respectively.

2. Death within 90 days occurred in 0.07% of patients in the aspirin group and 0.05% in the enoxaparin group.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Venous thromboembolism (VTE) occurs in approximately 2% of patients following hip and knee arthroplasty procedures. The use of aspirin for thromboprophylaxis has increased between 2010 and 2021 due to its low cost, perceived safety and ease of administration. However, limited evidence exists regarding the safety and efficacy of aspirin as a sole prophylactic agent, hence the objective of this study was to determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE after total hip arthroplasty (THA) or total knee arthroplasty (TKA). A total of 9711 patients undergoing THA or TKA were enrolled in this trial between April 2019 and December 2020. Patients were randomized to receive either 100mg/d of aspirin (n=5675) or 40mg/d of enoxaparin (n=4036) for 35 days post-THA and for 14 days post-TKA. The primary outcome in this study was symptomatic VTE within 90 days, which included pulmonary embolism and deep venous thrombosis. Secondary outcomes included death and major bleeding within 90 days. Within 90 days of surgery, symptomatic VTE occurred in 256 patients, with 79 cases of PE, 18 cases of above-knee DVT and 174 cases of below-knee DVT. The rate of symptomatic VTE in the aspirin group was 3.45%, and in the enoxaparin group it was 1.82%. A limitation to this study was the loss to follow-up at a rate of 5.2%, which could have led to some outcomes being missed. A strength of this study was its large sample size.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

Relevant Reading: Aspirin versus enoxaparin for the initial prevention of venous thromboembolism following elective arthroplasty of the hip or knee: a systematic review and meta-analysis

In-Depth [randomized controlled trial]: In this study, a total of 9711 patients were included (median age, 68 years; 56.8% female). Within 90 days of THA or TKA, symptomatic VTE occurred at a rate of 3.45% (187 of 5416 patients) in the aspirin group, and 1.82% (69 of 3787 patients) in the enoxaparin group (estimated difference, 1.97%; 95% CI, 0.54%-3.41%). This trial demonstrated significant superiority for enoxaparin (P=.007), and failed to meet the criterion for noninferiority for aspirin. Death within 90 days occurred in 4 of 5675 patients (0.07%) in the aspirin group and 2 of 4036 patients (0.05%) in the enoxaparin group (estimated difference, 0.05%; 95% CI, -0.05% to 0.15%). Major bleeding events occurred in 17 of 5401 patients (0.31%) in the aspirin group, and 15 of 3779 patients (0.40%) in the enoxaparin group (estimated difference, -0.05%; 95% CI, -0.25% to 0.04%). The median time to diagnosis of symptomatic VTE was 7.5 days (IQR, 5-19 days) in the aspirin group and 12 days (IQR, 7-25 days) in the enoxaparin group.

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