TY - JOUR
T1 - Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture
AU - O'Toole, Robert V
AU - Stein, Deborah M
AU - O'Hara, Nathan N
AU - Frey, Katherine P
AU - Taylor, Tara J
AU - Scharfstein, Daniel O
AU - Carlini, Anthony R
AU - Sudini, Kuladeep
AU - Degani, Yasmin
AU - Slobogean, Gerard P
AU - Haut, Elliott R
AU - Obremskey, William
AU - Firoozabadi, Reza
AU - Bosse, Michael J
AU - Goldhaber, Samuel Z
AU - Marvel, Debra
AU - Castillo, Renan C
AU - Major Extremity Trauma Research Consortium (METRC)
A2 - von Keudell, Arvind Gabriel
N1 - Copyright © 2023 Massachusetts Medical Society.
PY - 2023/1/19
Y1 - 2023/1/19
N2 - BACKGROUND: Clinical guidelines recommend low-molecular-weight heparin for thromboprophylaxis in patients with fractures, but trials of its effectiveness as compared with aspirin are lacking.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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 ClinicalTrials.gov number, NCT02984384.).
AB - BACKGROUND: Clinical guidelines recommend low-molecular-weight heparin for thromboprophylaxis in patients with fractures, but trials of its effectiveness as compared with aspirin are lacking.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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 ClinicalTrials.gov number, NCT02984384.).
KW - Adult
KW - Humans
KW - Middle Aged
KW - Anticoagulants/adverse effects
KW - Aspirin/adverse effects
KW - Chemoprevention/methods
KW - Extremities/injuries
KW - Fractures, Bone/complications
KW - Hemorrhage/etiology
KW - Heparin, Low-Molecular-Weight/adverse effects
KW - Hip Fractures/complications
KW - Pelvic Bones/injuries
KW - Pragmatic Clinical Trials as Topic
KW - Pulmonary Embolism/etiology
KW - Spinal Fractures/complications
KW - Venous Thromboembolism/etiology
KW - Venous Thrombosis/etiology
UR - http://www.scopus.com/inward/record.url?scp=85146531987&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2205973
DO - 10.1056/NEJMoa2205973
M3 - Journal article
C2 - 36652352
SN - 0028-4793
VL - 388
SP - 203
EP - 213
JO - The New England journal of medicine
JF - The New England journal of medicine
IS - 3
ER -