Aspirin versus low molecular weight heparin in major orthopedic surgery: a meta-analysis of randomized controlled trials

Whether aspirin is comparable to low molecular weight heparin (LMWH) in preventing venous thromboembolism (VTE) after major orthopedic surgery remains controversial. This meta-analysis aims to systematically evaluate the efficacy and safety of aspirin versus LMWH for the prevention of deep vein thrombosis (DVT) following major orthopedic surgery. Randomized controlled trials (RCTs) comparing aspirin with LMWH in patients undergoing major orthopedic surgery (including total hip arthroplasty and total knee arthroplasty) from inception to August 2025 were systematically searched in electronic databases including PubMed, Cochrane Library, EMbase, CNKI, WanFang, and VIP. Literature was managed using EndNote X9 , and meta-analysis was performed using RevMan 5.3 software. Primary outcome measures included pulmonary embolism (PE), DVT, major bleeding events, minor bleeding events, wound complications, all-cause mortality within 90 days postoperatively, and postoperative blood loss. A total of 13 RCTs involving 13,411 patients were included, with 7,160 patients in the aspirin group and 6,251 in the LMWH group. The overall meta-analysis showed a significantly higher incidence of PE in the aspirin group than in the LMWH group (OR = 1.61, 95% CI: 1.04–2.50, P = 0.03). The common-effect GLMM produced a similar full-model estimate (OR = 1.61, 95% CI: 1.04–2.55); however, leave-one-out omission of the largest study (Sidhu 2022) removed statistical significance and reversed the point estimate. For DVT, the random-effects GLMM showed no statistically clear difference (OR = 1.27, 95% CI: 0.73–2.09). Regarding safety outcomes, there were no statistically significant differences between groups in major bleeding events (OR = 0.90, 95% CI: 0.49–1.65, P = 0.73), wound complications (OR = 0.78, 95% CI: 0.45–1.35, P = 0.37), or 90-day all-cause mortality (OR = 1.01, 95% CI: 0.24–4.16, P = 0.99). Aspirin was associated with fewer minor bleeding events (OR = 0.58, 95% CI: 0.38–0.87, P = 0.009). Postoperative blood loss did not differ significantly between groups (MD = 39.50 mL, 95% CI: -0.49 to 79.49, P = 0.05). The pooled PE analysis favored LMWH, but the leave-one-out GLMM showed that this finding was influenced by the largest included trial and should therefore be interpreted cautiously. Evidence for DVT was inconclusive under the selected random-effects GLMM. Aspirin was associated with fewer minor bleeding events, whereas no statistically significant differences were observed in major bleeding, wound complications, or 90-day mortality. Not applicable.