Aspirin or LMWH Thromboprophylaxis After a Fracture

Quick Takes

  • Patients undergoing surgery for orthopedic limb fracture can be safely treated with either aspirin or LMWH for thromboprophylaxis.
  • While mortality rates were similar between the aspirin- and LMWH-treated groups, deep vein thrombosis was higher in the aspirin-treated group.
  • Overall rates of bleeding were modest but not different between the aspirin- and LMWH-treated groups.

Study Questions:

What is the effectiveness of aspirin as compared to low-molecular-weight heparin (LMWH) for thromboprophylaxis in patients with acute fractures?


PREVENT CLOT is a pragmatic, multicenter, randomized, noninferiority trial of adult patients with an acute fracture of an extremity (hip to midfoot or shoulder to wrist) that was treated operatively. The study also included patients with any pelvic or acetabular fracture, regardless of surgical intervention. Patients were randomly assigned to receive enoxaparin 30 mg twice daily or aspirin 81 mg twice daily while hospitalized. After hospital discharge, patients continued to receive their randomly assigned antithrombotic agent per hospital protocol. The primary outcome was all-cause death at 90 days. Secondary outcomes included nonfatal pulmonary embolism, deep vein thrombosis, and bleeding.


During the study period, 12,211 patients were randomized to receive aspirin (n = 6,101) or LMWH (n = 6,110). Patients had a mean (± standard deviation) age of 44.6 ± 17.8 years, 0.7% had a prior history of venous thromboembolism, and 2.5% had a history of cancer. Patients received a mean 8.8 ± 10.6 days of in-hospital thromboprophylaxis and a median 21 days of post-hospital thromboprophylaxis. The primary outcome (death at 90 days) occurred in 0.78% of patients in the aspirin group and 0.73% of patients in the LMWH group (p < 0.001 for noninferiority). Deep vein thrombosis occurred in 2.51% of patients in the aspirin group and 1.71% of patients in the LMWH group (difference, 0.80%; 95% confidence interval, 0.28-1.31%). Other outcomes were similar in both groups.


The authors concluded that in patients with extremity fractures treated operatively or inclusive of the pelvis/acetabulum, thromboprophylaxis with aspirin was noninferior to LMWH in preventing death and associated with a low rate of venous thromboembolism.


There has been much debate on the most appropriate thromboprophylaxis regimen for patients undergoing major orthopedic surgery or with orthopedic fractures. This randomized trial demonstrates noninferiority of aspirin as compared to LMWH for mortality but with a slightly increased rate of deep vein thrombosis. While many in the thrombosis community may still favor anticoagulant thromboprophylaxis, many in the orthopedic surgery and trauma surgery community will see this as supporting aspirin as first-line for thromboprophylaxis. Notably, the population in this study was quite young (mean age 45 years). Further analysis in older age patients and those with prior venous thromboembolism would be helpful to determine if LMWH is superior to aspirin in these higher thrombotic-risk patients.

Clinical Topics: Anticoagulation Management, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Anticoagulants, Aspirin, Enoxaparin, Fibrinolytic Agents, Fractures, Bone, General Surgery, Hemorrhage, Heparin, Low-Molecular-Weight, Hip Fractures, Neoplasms, Orthopedic Procedures, Patient Discharge, Post-Exposure Prophylaxis, Pulmonary Embolism, Secondary Prevention, Thrombosis, Vascular Diseases, Venous Thromboembolism, Venous Thrombosis

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