A randomized clinical trial of more than 12,000 patients treated at medical centers in the US and Canada suggests aspirin was as effective as low-molecular-weight heparin for preventing life-threatening blood clots in patients hospitalized with fractures.
A noninferiority trial of adults who had a fracture of an extremity treated operatively or who had any pelvic or acetabular fracture, results of the study indicate use of aspirin was noninferior for preventing death and was associated with low incidences of deep-vein thrombosis and pulmonary embolism.
“Many patients with fractures will likely strongly prefer to take a daily aspirin over receiving injections after we found that both give them similar outcomes for prevention of the most serious outcomes from blood clots,” said lead investigator Robert V. O’Toole, MD, chief of Orthopaedics at the R Adams Cowley Shock Trauma Center at the University of Maryland Medical Center (UMMC), in a statement from UMMC. “We expect our findings from this large-scale trial to have an important impact on clinical practice that may even alter the standard of care.”
Led by Toole, along with collaborators from UMMC and the Major Extremity Trauma Research Consortium, the Prevention of Clot in Orthopaedic Trauma (PREVENT CLOT) trial was designed pragmatic, multicenter, randomized, noninferiority trial that enrolled the aforementioned patient population and randomized them to low-molecular-weight heparin (enoxaparin) 30 mg twice daily or aspirin 81 mg twice daily during hospitalization. In total, the trial enrolled 12,211 patients from 21 trauma centers in the US and Canada between April 2017 and August 2021, with 6101 patients randomized to aspirin and 6110 randomized to low-molecular-weight heparin.
The study cohort had a mean age of 44.6±17.8 years, 0.7% had a history of venous thromboembolism, and 2.5% had a history of cancer. When examining thromboprophylaxis trends, investigators found the mean duration of in-hospital thromboprophylaxis was 8.8±10.6 days and the median duration of thromboprophylaxis prescribed at discharge was a 21-day supply. Per trial protocol, post-discharge thromboprophylaxis was conducted according to the protocols of each trauma center. The primary outcome of interest for the trial was all-cause mortality at 90 days. Secondary outcomes of interest included the incidence of nonfatal pulmonary embolism, deep vein thrombosis, and bleeding complications.
Upon analysis, a total of 47 (0.78%) deaths occurred among the aspirin group and 45 patients in the low-molecular-weight heparin group (difference, 0.05 percentage points [96.2% CI, -0.27 to 0.38]; P <.001 for a noninferiority margin 0.75 percentage points. Analysis of secondary outcomes indicated pulmonary embolism occurred in 90 patients (90-day probability, 1.49%) among the aspirin group and in 90 patients (90-day probability, 1.49%) among the low-molecular-weight heparin group (difference, 0.00 percentage points [95% CI, -0.43 to 0.43]). Further analysis indicated deep vein thrombosis occurred in 2.51% of patients among the aspirin group and 1.71% among the low-molecular-weight heparin group (difference, 0.80 percentage points [95% CI, 0.28 to 1.31]). Evaluation of bleeding complications and serious adverse indicated event rates were similar between the study arms.
“This relatively small difference was driven by clots lower in the leg, which are thought to be of less clinical significance and often do not require treatment,” said study investigator Deborah Stein, MD, MPH, professor of Surgery at UMSOM and director of Adult Critical Care Services at UMMC.
This study, “Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture,” was published in the New England Journal of Medicine.