Comparing Two Medicines to Prevent Blood Clots after Treatment for Fractures – The PREVENT CLOT Study [Internet]

Excerpt

Background: Clinical guidelines recommend low-molecular-weight heparin (LMWH) for thromboprophylaxis in hospitalized patients with a fracture, but trials comparing its effectiveness against aspirin are lacking.

Objectives: Our 3 aims were to compare thromboprophylaxis with aspirin with LMWH in patients with orthopedic trauma with respect to (1) all-cause mortality; (2) nonfatal pulmonary embolism and deep vein thrombosis and (3) bleeding events, wound complications, or deep surgical site infection. Our secondary aims were to compare aspirin with LMWH with respect to (1) patient medication satisfaction, (2) out-of-pocket costs, and (3) inpatient medication adherence.

Methods: We performed a pragmatic, multicenter, randomized trial involving patients with an operatively treated extremity fracture or any pelvis or acetabular fracture regardless of operative treatment. Enrolled patients were randomly assigned to receive 30 mg LMWH (enoxaparin) twice daily or 81 mg aspirin twice daily. After discharge, the duration of thromboprophylaxis was at the treating physician's discretion. The primary outcome was 90-day all-cause mortality as assessed with Kaplan-Meier curves and a noninferiority margin of 0.75%, with an expected event rate of 1.00%. Secondary clinical outcomes were compared based on cumulative incidence functions at 90 days. Differences in patient satisfaction and out-of-pocket costs were compared via cumulative logit models. We used logistic regression to estimate between-group differences in adherence. Patients, clinicians, and local research staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation.

Results: A total of 12 211 patients (6101 assigned to aspirin and 6110 assigned to LMWH) were included in the primary analysis. Forty-seven of 6101 patients (0.78%) in the aspirin group died, and 45 of 6110 patients (0.73%) in the LMWH group died (difference, 0.05% [96.2% CI, −0.27% to 0.38%]; P < .001 for a 0.75% noninferiority margin). Nonfatal pulmonary embolism occurred in 90 patients (1.49%) in the aspirin group and 90 patients (1.49%) in the LMWH group (difference, 0.00% [95% CI, −0.43% to 0.43%]). Deep vein thrombosis occurred in 151 patients (2.51%) in the aspirin group and 103 patients (1.71%) in the LMWH group (difference, 0.80% [95% CI, 0.28%-1.31%]). The 90-day rates of bleeding complication (difference, −0.54% [95% CI, −1.78% to 0.69%]), wound complications (difference, −0.10% [95% CI, −0.25% to 0.05%]), and infections (difference, 0.18% [95% CI, −0.28% to 0.64%]) did not differ between groups. Patient medication satisfaction was higher in patients assigned to aspirin (odds ratio [OR], 2.59 [95% CI, 2.39-2.80]; P < .001). Out-of-pocket costs did not differ between groups (OR, 0.99 [95% CI, 0.90-1.08]; P = .78). The odds of adherence were 68% higher in patients assigned to aspirin (OR, 1.68 [95% CI, 1.51-1.87]; P < .001).

Conclusions: Among patients with an operatively treated extremity fracture or any pelvis or acetabular fracture, thromboprophylaxis with aspirin was noninferior to LMWH in preventing death.

Limitations: Because of the critical injuries of the study population, we allowed eligible patients to receive up to 2 doses of LMWH before consent. Because of the pragmatic design and desire for the results to be generalizable, we did not mandate the criteria or duration of postdischarge thromboprophylaxis.