Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture

Author(s): Major Extremity Trauma Research Consortium (METRC)*
Source: N Engl J Med 2023; 388:203-213 DOI: 10.1056/NEJMoa2205973
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

ASA vs. LMWH prophylaxis after an extremity fracture requiring surgery or a pelvic fracture. ASA was non-inferior to LMWH, and death rates were equivalent; however, DVT rates were higher (2.5%) in the ASA group vs. the LMWH group (1.7%), while PE and bleeding rates were similar. I think ASA has a role for some patients in various high-risk settings.


Clinical guidelines recommend low-molecular-weight heparin for thromboprophylaxis in patients with fractures, but trials of its effectiveness as compared with aspirin are lacking.


In this pragmatic, multicenter, randomized, noninferiority trial, we enrolled patients 18 years of age or older who had a fracture of an extremity (anywhere from hip to midfoot or shoulder to wrist) that had been treated operatively or who had any pelvic or acetabular fracture. Patients were randomly assigned to receive low-molecular-weight heparin (enoxaparin) at a dose of 30 mg twice daily or aspirin at a dose of 81 mg twice daily while they were in the hospital. After hospital discharge, the patients continued to receive thromboprophylaxis according to the clinical protocols of each hospital. The primary outcome was death from any cause at 90 days. Secondary outcomes were nonfatal pulmonary embolism, deep-vein thrombosis, and bleeding complications.


A total of 12,211 patients were randomly assigned to receive aspirin (6101 patients) or low-molecular-weight heparin (6110 patients). Patients had a mean (±SD) age of 44.6±17.8 years, 0.7% had a history of venous thromboembolism, and 2.5% had a history of cancer. Patients received a mean of 8.8±10.6 in-hospital thromboprophylaxis doses and were prescribed a median 21-day supply of thromboprophylaxis at discharge. Death occurred in 47 patients (0.78%) in the aspirin group and in 45 patients (0.73%) in the low-molecular-weight–heparin group (difference, 0.05 percentage points; 96.2% confidence interval, −0.27 to 0.38; P<0.001 for a noninferiority margin of 0.75 percentage points). Deep-vein thrombosis occurred in 2.51% of patients in the aspirin group and 1.71% in the low-molecular-weight–heparin group (difference, 0.80 percentage points; 95% CI, 0.28 to 1.31). The incidence of pulmonary embolism (1.49% in each group), bleeding complications, and other serious adverse events were similar in the two groups.


In patients with extremity fractures that had been treated operatively or with any pelvic or acetabular fracture, thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin in preventing death and was associated with low incidences of deep-vein thrombosis and pulmonary embolism and low 90-day mortality. (Funded by the Patient-Centered Outcomes Research Institute; PREVENT CLOT number, NCT02984384. opens in new tab.)

Author Affiliations

The members of the writing committee (Robert V. O’Toole, M.D., Deborah M. Stein, M.D., M.P.H., Nathan N. O’Hara, Ph.D., Katherine P. Frey, Ph.D., R.N., Tara J. Taylor, M.P.H., Daniel O. Scharfstein, Sc.D., Anthony R. Carlini, M.S., Kuladeep Sudini, Ph.D., Yasmin Degani, M.P.H., Gerard P. Slobogean, M.D., M.P.H., Elliott R. Haut, M.D., Ph.D., William Obremskey, M.D., M.P.H., Reza Firoozabadi, M.D., Michael J. Bosse, M.D., Samuel Z. Goldhaber, M.D., Debra Marvel, M.A., and Renan C. Castillo, Ph.D.) assume responsibility for the overall content and integrity of this article.

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