Aspirin vs. enoxaparin for thromboprophylaxis after total hip arthroplasty, total knee arthroplasty, or hip fracture surgery—a systematic review and meta-analysis

Objective To systematically evaluate the efficacy and safety of aspirin vs. enoxaparin for the prevention of venous thromboembolism (VTE) following major orthopedic surgeries. Methods We systematically searched PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, and CQVIP (VIP) databases from their inception until August 2025 for randomized controlled trials (RCTs) and cohort studies comparing aspirin with enoxaparin for thromboprophylaxis in patients undergoing major orthopedic surgeries (total hip/knee arthroplasty, hip fracture surgery). Two researchers independently performed literature screening, data extraction, and risk-of-bias assessment for the included studies. A meta-analysis was conducted using Review Manager (RevMan) version 5.3 software. Results A total of studies involving 126,367 patients (43,441 in the aspirin group and 82,926 in the enoxaparin group) were included. Regarding efficacy, the initial meta-analysis showed no significant difference in the incidence of pulmonary embolism (PE; odds ratio [OR] = 1.14, 95% CI: 0.66–1.95) or deep vein thrombosis (DVT; primary analysis: Test for overall effect: Z = 0.43, p = 0.67). However, sensitivity analyses after removing key contributors to heterogeneity revealed that the incidence of DVT was significantly lower in the enoxaparin group (OR = 0.78, 95% CI: 0.64–0.96, p = 0.02), while the incidence of PE was significantly higher in the aspirin group (sensitivity analysis: Test for overall effect: Z = 2.30, p = 0.02). Regarding safety, the risks of both major bleeding (OR = 0.60, 95% CI: 0.40–0.89, p = 0.01) and minor bleeding (OR = 0.57, 95% CI: 0.49–0.66, p < 0.00001) were significantly lower in the aspirin group. No statistically significant differences were found between the two groups in terms of wound complications, 90-day all-cause mortality (primary analysis: OR = 0.81, 95% CI: 0.37–1.78, p = 0.60), or readmission rates. Conclusion For patients undergoing major orthopedic surgery, aspirin is comparable to enoxaparin in preventing the primary efficacy outcomes of VTE (pulmonary embolism and deep vein thrombosis) but demonstrates a significant advantage in reducing the risk of minor bleeding. Aspirin represents an effective and safer prophylactic option, particularly for patients with higher bleeding risk profiles.