Aspirin was noninferior to the standard of care of low molecular weight heparin (LMWH) for rates of mortality and pulmonary embolism (PE) among patients with a limb fracture requiring surgery or a pelvic or acetabular fracture, according to the results of the randomized PREVENT CLOT study published in the New England Journal of Medicine.

“Our results are clinically meaningful,” the authors wrote in their report. “Patients with orthopedic trauma strongly favor aspirin over LMWH because of the lower costs and less burdensome administration of aspirin.”

The multicenter, noninferiority PREVENT CLOT trial randomly assigned 12,211 adult patients with an extremity fracture that required surgery or a pelvic or acetabular fracture to receive thromboprophylaxis with aspirin (81 mg twice daily) or enoxaparin. All patients received their assigned thromboprophylaxis in the hospital and continued their prophylaxis after discharge according to local hospital policy. The primary endpoint was death from any cause at 90 days and secondary endpoints included nonfatal PE, DVT, and bleeding.

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The mean age at baseline was 45 and 62% of patients were male. There were 63% of patients who were non-Hispanic White, 20% who were non-Hispanic Black, and 12% who were Hispanic. There were 0.7% of patients with a history of venous thromboembolism. The most common sites of fracture were lower extremity (87.5%), upper extremity (27.4%), thorax (18.4%), face (13.8%), head (12.8%), abdomen (12.8%), and spine (10.3%).

The rate of death from any cause in the aspirin group was 0.78%, which was noninferior to the rate of 0.73% in the LMWH group (difference, 0.05%; 95% CI, -0.27% to 0.38%; P <.001). Aspirin was also noninferior to LMWH for PE with rates of 1.49% in both groups (difference, 0; 95% CI, -0.43% to 0.43%).

However, deep vein thrombosis (DVT) occurred more frequently with aspirin, with a rate of 2.51% compared with 1.71% with LMWH (difference, 0.80; 95% CI, 0.28% to 1.31%).

The safety outcomes were similar between the groups. Bleeding complications occurred among 13.7% of patients in the aspirin group and 14.3% of patients in the LMWH group (difference, -0.54; 95% CI, -1.78% to 0.69%).

The authors concluded that “thromboprophylaxis with aspirin was noninferior to LMWH in preventing death and was associated with low incidences of DVT and PE and low 90-day mortality.”


Major Extremity Trauma Research Consortium (MERTC). Aspirin or low-molecular-weight heparin for thromboprophylaxis after a fracture. N Engl J Med. 2023;388:203-213. doi: 10.1056/NEJMoa2205973