Cost-Effectiveness Thresholds for Venous Thromboembolism Prophylaxis in Ankle Fracture Surgery: A Break-Even Analysis

Background: The role of venous thromboembolism (VTE) chemoprophylaxis following ankle fracture surgery remains controversial. Although pharmacologic prophylaxis is standard in major orthopaedic procedures, its utility in foot and ankle trauma surgery is unclear because of low reported VTE rates and potential bleeding risks. Furthermore, no consensus exists on the cost-effectiveness of prophylactic agents in this population. Methods: A literature review and the TriNetX Research Network were used to identify postoperative symptomatic VTE rates following ankle open reduction internal fixation (ORIF). The cost of treating a symptomatic VTE was estimated from existing literature and adjusted to 2025 US dollars. Drug pricing data were obtained from an online pharmacy database. A break-even analysis was conducted to calculate the absolute risk reduction (ARR) and number needed to treat (NNT) for each agent to be cost-effective. A subanalysis compared 30-day bleeding and transfusion rates between patients who received prophylaxis and those who did not. Results: The low and high literature-based VTE rates were 0.33% and 1.2%, whereas the TriNetX-derived VTE rate was 0.56%. Among 64 184 patients undergoing ankle ORIF without prophylaxis, 384 developed a symptomatic VTE. Aspirin (81 mg and 325 mg) and warfarin (5 mg) were cost-effective at all 3 VTE rates, with NNTs ranging from 9217 to 10 547. Enoxaparin (40 mg) was only cost-effective at the highest VTE rate (NNT = 131), whereas rivaroxaban (20 mg) was not cost-effective at any rate. Enoxaparin and rivaroxaban became cost-effective only when VTE treatment costs exceeded $50 000 and $1 500 000, respectively. Patients receiving prophylaxis had higher bleeding (0.56% vs 0.26%) and transfusion (0.82% vs 0.25%) rates ( P < .001). Conclusion: In summary, this study found that aspirin 81 mg, aspirin 325 mg, and warfarin are cost-effective for VTE chemoprophylaxis following ankle fracture fixation. Enoxaparin and rivaroxaban are generally not cost-effective, and their use may be appropriate only in high-risk patients. Level of Evidence: Level IV, economic analysis.