Twice-Daily Low-Dose Aspirin Is Similar to Enoxaparin for Thromboprophylaxis After Inpatient Treatment for Fracture

Clinical Question

Is twice-daily low-dose aspirin noninferior to enoxaparin, a low-molecular-weight heparin, for thromboprophylaxis after an extremity, acetabular, or pelvic fracture?

Bottom Line

Aspirin is noninferior to enoxaparin for thromboprophylaxis following inpatient treatment of a fracture. It is more affordable and convenient and preferred by patients. (Level of Evidence = 1b)

Synopsis

The large pragmatic trial included 12,211 adults with an extremity fracture treated operatively, or a pelvic or acetabular fracture treated with or without surgery. The patients were randomized to receive aspirin, 81 mg twice daily, or enoxaparin, 30 mg twice daily. The patients received the assigned medication while in the hospital and then followed their hospital's postdischarge thromboprophylaxis protocol. Patients with fractures of the hands or feet, who had already received three or more doses of thromboprophylaxis, or those admitted more than 48 hours after the injury were excluded. Patients taking an anticoagulant on admission or who had a venous thromboembolism in the past three months were also excluded. At baseline, the mean age of participants was 45 years, 62% were men, and 20% were Black. The most common site of injury was the lower extremity, and 67% of patients had only a lower extremity fracture. Groups were balanced at the start of the study, and analysis was by intention to treat. The primary outcome of 90-day all-cause mortality occurred in 0.78% of patients in the aspirin group and 0.73% in the enoxaparin group (95% CI for the difference, −0.27 to 0.38). There was no difference in the likelihood of any pulmonary embolism (1.49% in each group), but there was an increase in deep venous thromboses in the aspirin group (2.51% vs. 1.71%; 95% CI for difference, 0.28 to 1.31; number needed to harm = 125), although most of the increase was in distal clots. There was no difference in the rate of bleeding complications, infections, or wound complications.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location)

Reference: O'Toole RV, Stein DM, O'Hara NN, et al.; Major Extremity Trauma Research Consortium (METRC). Aspirin or low-molecular-weight heparin for thromboprophylaxis after a fracture. N Engl J Med. 2023;388(3):203-213.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.