Thromboprophylaxis after fractures: aspirin is noninferior to LMWH in reducing mortality

Aspirin or low-molecular-weight heparin for thromboprophylaxis after a fracture

Literature - Major Extremity Trauma Research Consortium (METRC) - N Engl J Med. 2023 Jan 19. DOI: 10.1056/NEJMoa2205973

Introduction and methods


Patients with traumatic orthopedic injuries are at risk to develop venous thromboembolism, which may be potentially fatal [1-2]. Thromboprophylaxis therapy such as subcutaneous administration of low-molecular-weight heparin (LMWH) is recommended to these patients to reduce the risk of death and venous thromboembolism-related complications [3]. Aspirin, which is cheap and orally administrated, may be an alternative thromboprophylaxis to LMWH in patients with operatively-treated fractures.

Aim of the study

The authors examined the effectiveness and safety of aspirin as compared to LMWH for thromboprophylaxis in patients with fractures at day 90 after study inclusion.


The PREVENT CLOT (Prevention of Clot in Orthopaedic Trauma) trial was a pragmatic, multicenter, randomized, noninferiority trial conducted in the United States and Canada. A total of 12,221 patients of 18 years of age and older with an operatively-treated extremity fracture or any fracture to the pelvis or acetabulum were enrolled in the study. Hospitalized patients were randomly assigned to receive LMWH (enoxaparin) at a dose of 30 mg twice daily (6110 patients) or aspirin at a dose of 81 mg twice daily (6101 patients). After discharge, thromboprophylaxis was continued according to local protocols.


The primary outcome was death from any cause at 90 days. Secondary efficacy outcomes were cause-specific death, nonfatal pulmonary embolism (PE), and deep-vein thrombosis. Cause-specific death was classified as related to PE, possibly related to PE, and unlikely to be related to PE. Secondary safety outcomes were bleeding events, wound complications, and surgical-site infections.

Main results

  • Treatment duration was similar in both treatment groups. Patients in the aspirin group received a mean of 8.6 ± 10.6 in-hospital doses, and patients in the LMWH group received a mean of 9.1 ± 10.5 in-hospital doses. The median prescribed supply of thromboprophylaxis at discharge was in both groups 21 days.
  • Death from any cause occurred to a similar extent in both treatment groups. In the aspirin group 47 patients (0.78%) died compared to 45 patients (0.73%) in the LMWH group (difference 0.05%; 96.2% CI, −0.27 to 0.38; P <0.001, noninferiority margin of 0.75%).
  • There was no difference in cause-specific death between both treatment groups. Death related to PE, possibly related to PE, and unlikely to be related to PE, was similar in the aspirin group and the LMWH group (difference -0.02%, 0.08, and -0.03, respectively).
  • The incidence of nonfatal PE was similar in the aspirin group and in the LMWH group (90 patients in both groups, 1.49%; difference 0.00%; 95% CI, -0.43 to 0.43).
  • Deep-vein thrombosis was slightly more prevalent in the aspirin group compared to the LMWH group (151 patients (2.51%) versus 103 patients (1.71%) respectively; difference 0.80%; 95% CI, 0.28-1.31).
  • The incidence of bleeding events, wound complications, and surgical-site infections were similar in the aspirin group and in the LMWH group.


The PREVENT CLOT trial demonstrated that aspirin is noninferior to LMWH for the prevention of death in patients with fractures. The incidence of PE was similar in both treatment groups. However, the incidence of deep-vein thrombosis was slightly higher, but non-significant in aspirin treated-patients. Health care providers and patients should weigh this risk against the financial and practical benefits of aspirin.


1. Geerts WH, Code KI, Jay RM, et al. A prospective study of venous thromboembolism after major trauma. N Engl J Med 1994;331:1601-1606.

2. Barrera LM, Perel P, Ker K, et al. Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev 2013;3:CD008303.

3. Sagi HC, Ahn J, Ciesla D, et al. Venous thromboembolism prophylaxis in orthopaedic trauma patients: a survey of OTA member practice patterns and OTA expert panel recommendations. J Orthop Trauma 2015;29:e355–e362.

Find this article online at N Engl J Med.

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