Efficacy and Safety of Aspirin Versus Low-Molecular-Weight Heparin for the Prevention of Pulmonary Embolism in High-Risk Orthopedic Surgery Patients: A Meta-Analysis
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Abstract
Background: Pulmonary embolism and venous thromboembolism remain important preventable complications after high-risk orthopedic surgery, particularly following arthroplasty, fracture fixation, revision procedures, and orthopedic trauma. Aspirin and low-molecular-weight heparin are widely used thromboprophylactic agents, but their comparative efficacy and safety remain clinically debated because thrombotic protection must be balanced against bleeding risk, administration burden, cost, and patient adherence. Objective: This systematic review and meta-analysis aimed to compare the efficacy and safety of aspirin versus low-molecular-weight heparin for prevention of pulmonary embolism, overall venous thromboembolism, bleeding complications, and mortality in patients undergoing high-risk orthopedic surgery. Methods: A systematic search was conducted in PubMed, ScienceDirect, SpringerLink, Wiley Online Library, BMJ Journals, Cochrane Library, and Google Scholar for English-language comparative studies published from January 2013 to March 2026. Eligible studies included randomized controlled trials, secondary analyses of randomized trials, cohort studies, and comparative clinical studies directly evaluating aspirin-based thromboprophylaxis against low-molecular-weight heparin in orthopedic surgical populations. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool for randomized evidence and the Newcastle–Ottawa Scale for cohort studies. Dichotomous outcomes were synthesized using risk ratios with 95% confidence intervals where extractable data were available. Results: Twelve comparative studies were included, covering orthopedic trauma, arthroplasty, revision surgery, pelvic fracture, obese total knee arthroplasty, and anterior cruciate ligament reconstruction populations. Aspirin and low-molecular-weight heparin showed broadly comparable effectiveness for pulmonary embolism and overall venous thromboembolism prevention. Low-molecular-weight heparin showed a tendency toward stronger thromboembolic protection in higher-risk groups, whereas aspirin demonstrated a more favorable bleeding and usability profile. No consistent mortality difference was observed. Conclusion: Aspirin and low-molecular-weight heparin are both clinically relevant thromboprophylaxis options after high-risk orthopedic surgery. Current evidence supports individualized, risk-stratified prophylaxis selection based on thrombotic risk, bleeding risk, surgical context, and patient-centered feasibility
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1. Schousboe JT, Brown GA. Cost-effectiveness of low-molecular-weight heparin compared with aspirin for prophylaxis against venous thromboembolism after total joint arthroplasty. J Bone Joint Surg Am. 2013;95(14).
2. Zhu L, et al. Effectiveness and safety of rivaroxaban or low-molecular-weight heparin in non-major orthopedic surgery: a meta-analysis of randomized controlled trials. J Orthop Surg Res. 2024.
3. Yazdi H, et al. Aspirin is as effective as low molecular weight heparins in preventing symptomatic venous thromboembolism following arthroscopic anterior cruciate ligament reconstruction. BMC Musculoskelet Disord. 2024.
4. O’Hara NN, et al. Risk-stratified thromboprophylaxis effects of aspirin versus low-molecular-weight heparin in orthopedic trauma patients: a secondary analysis of the PREVENT CLOT trial. Trauma Surg Acute Care Open. 2024.
5. Hovik O, et al. Prevention of venous thromboembolism in high-risk patients continuing their dose of 75 mg aspirin compared to healthier patients given low-molecular-weight heparin. J Arthroplasty. 2021;36.
6. Mirahmadi A, et al. Comparison of low molecular weight heparin, aspirin, and their combination for the prevention of thrombosis after total knee arthroplasty in obese patients. J Orthop Surg Res. 2025.
7. Asopa V, et al. Staged venous thromboembolic events prophylaxis with low-molecular-weight heparin followed by aspirin is safe and effective after arthroplasty. ANZ J Surg. 2015.
8. Zhu J, et al. Low-molecular-weight heparin for the prevention of venous thromboembolism in patients undergoing knee arthroscopic surgery and anterior cruciate ligament reconstruction. Am J Sports Med. 2019.
9. Mohamed A, et al. Low-molecular-weight heparin in orthopedic patients taking clopidogrel: a focused review. Cureus. 2025.
10. Chapelle C, et al. Prevention of venous thromboembolic events with low-molecular-weight heparin in the non-major orthopaedic setting: meta-analysis of randomized controlled trials. Orthop Traumatol Surg Res. 2014.
11. Núñez JH, et al. [Translated article] Risk of venous thromboembolism in thromboprophylaxis between aspirin and low molecular weight heparins after total hip arthroplasty or total knee arthroplasty. Rev Esp Cir Ortop Traumatol. 2024.
12. Poacher AT, et al. The impact of adopting low-molecular-weight heparin in place of aspirin as routine thromboprophylaxis for patients with hip fracture. Postgrad Med J. 2023.
13. Jones A, Al-Horani RA. Venous thromboembolism prophylaxis in major orthopedic surgeries and factor XIa inhibitors. Med Sci. 2023;11.
14. Zee AAG, et al. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization. Cochrane Database Syst Rev. 2017.
15. D’Astous J, Liederman Z, Douketis JD. Venous thromboembolism prophylaxis in high-risk orthopedic and cancer surgery. Postgrad Med. 2021;133.
16. Hong Z, et al. Aspirin is as effective and safe as oral anticoagulants for venous thromboembolism prophylaxis after joint arthroplasty: a systematic review and meta-analysis. J Bone Joint Surg Am. 2025.
17. Mahmud SA, et al. Aspirin versus enoxaparin for deep vein thrombosis prevention after orthopedic surgery: a review of efficacy and safety. J Immunother Med Sci. 2024.
18. Marcucci M, et al. Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery: systematic review and network meta-analysis. BMJ. 2022;379.
19. Lavu MS, et al. Low-dose aspirin is the safest prophylaxis for prevention of venous thromboembolism after total knee arthroplasty across all patient risk profiles. J Bone Joint Surg Am. 2024.
20. Stewart DW, Freshour JE. Aspirin for the prophylaxis of venous thromboembolic events in orthopedic surgery patients: a comparison of the AAOS and ACCP guidelines with review of the evidence. Ann Pharmacother. 2013;47(1):63-74.