Aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis in orthopaedic trauma patients: A patient-centered randomized controlled trial

• Published in: PloS one 2020-08, Vol.15 (8), p.e0235628-e0235628
• Main Authors: Haac, Bryce E, O'Hara, Nathan N, Manson, Theodore T, Slobogean, Gerard P, Castillo, Renan C, O'Toole, Robert V, Stein, Deborah M
• Format: Article
• Language: English
• Subjects: Acetabulum; Anticoagulants; Aspirin; Biology and Life Sciences; Bleeding; Blood transfusions; Care and treatment; Clinical trials; Comparative analysis; Complications; Complications and side effects; Consent; Dosage and administration; Drug dosages; Embolism; Emergency medical services; Fractures (Injuries); Heparin; Injury analysis; Joint surgery; Low molecular weight heparin; Medical imaging; Medicine; Medicine and Health Sciences; Methods; Oral administration; Orthopedics; Patient-centered care; Patients; Pelvis; Preferences; Prevention; Prophylaxis; Pulmonary embolisms; Randomization; Rank tests; Research and Analysis Methods; Risk factors; Statistical analysis; Supervision; Surgical site infections; Thromboembolism; Thrombosis; Trauma; Trauma centers; Veins & arteries; Venous thrombosis; Weight
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0235628

Emerging evidence suggests aspirin may be an effective venous thromboembolism (VTE) prophylaxis for orthopaedic trauma patients, with fewer bleeding complications. We used a patient-centered weighted composite outcome to globally evaluate aspirin versus low-molecular-weight heparin (LMWH) for VTE prevention in fracture patients. We conducted an open-label randomized clinical trial of adult patients admitted to an academic trauma center with an operative extremity fracture, or a pelvis or acetabular fracture. Patients were randomized to receive LMWH (enoxaparin 30-mg) twice daily (n = 164) or aspirin 81-mg twice daily (n = 165). The primary outcome was a composite endpoint of bleeding complications, deep surgical site infection, deep vein thrombosis, pulmonary embolism, and death within 90 days of injury. A Global Rank test and weighted time to event analysis were used to determine the probability of treatment superiority for LMWH, given a 9% patient preference margin for oral administration over skin injections. Overall, 18 different combinations of outcomes were experienced by patients in the study. Ninety-nine patients in the aspirin group (59.9%) and 98 patients in the LMWH group (59.4%) were event-free within 90 days of injury. Using a Global Rank test, the LMWH had a 50.4% (95% CI, 47.7-53.2%, p = 0.73) probability of treatment superiority over aspirin. In the time to event analysis, LMWH had a 60.5% probability of treatment superiority over aspirin with considerable uncertainty (95% CI, 24.3-88.0%, p = 0.59). The findings of the Global Rank test suggest no evidence of superiority between LMWH or aspirin for VTE prevention in fracture patients. LMWH demonstrated a 60.5% VTE prevention benefit in the weighted time to event analysis. However, this difference did not reach statistical significance and was similar to the elicited patient preferences for aspirin.