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

Abstract

Background 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. Methods 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. Results 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). Conclusion 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.

Recommendations from the ICM-VTE: Hip & Knee

“…Moreover, SSI definitions demonstrate variety across the studies in the literature, further compromising the comparisons of pooled results. Finally, most publications have investigated VTE prophylaxis within a specific subset of the orthopaedic population: those undergoing TJA surgery 347 . Considering that most of the relevant current published evidence demonstrates heterogeneity and a high risk of bias, additional level one studies are needed to truly evaluate the associations between VTE prophylaxis and SSI across all orthopaedic surgery subspecialties 350 .…”

“…No difference was identified in infection rates between the two groups, but patients were nearly eight times more likely to experience a wound complication whilst receiving LMWH as opposed to ASA. Haac et al, recently conducted an open-label RCT of adult patients admitted to an academic trauma center with operative extremity fractures, or a pelvis or acetabular fracture, comparing ASA with LMWH 347 . Deep infections were identified in 4.3% of patients receiving ASA, and in 5.5% in those receiving LMWH.…”

Perioperative air travel increases the risk of venous thromboembolism following lower limb arthroplasty

“…Thromboprophylaxis for our patients was, in keeping with current national guidelines, undertaken with one of two agents for differing time periods. We did not collect data on how many patients were prescribed either dalteparin or aspirin on discharge, though notably, large-scale meta-analyses and randomised controlled trials have shown no difference in the clinical effectiveness of these agents following both lower limb arthroplasty and trauma [31][32][33]; hence, we would not expect any difference in effectiveness of these agents in our cohort. Equally, we did not extend the thromboprophylaxis regimen in the TKA group to 5 weeks, as this would expose this cohort to a risk of complications for no benefit in terms of reduced VTE risk.…”

PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT): a randomised pragmatic trial protocol comparing aspirin versus low-molecular-weight heparin for blood clot prevention in orthopaedic trauma patients

“…The study is designed to enrol 12 200 patients. Assuming an estimated risk of death in the LMWH arm of 1.0%, 37 38 the proposed sample size provides 95% power to demonstrate the non-inferiority of aspirin with a non-inferiority margin of 0.75% at the upper bound of a two-sided 96.2% CI, as compared with LMWH. These calculations account for two interim analyses and allow for an attrition rate up to 7.5%.…”