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According to the Centers for Disease Control and Prevention (CDC), venous thromboembolism (VTE) causes as many as 100,000 deaths in the US each year. Patients who experience fractures that require surgery – an estimated 1 million people in the US annually – are at increased risk of developing VTE, including a fatal pulmonary embolism.

To prevent VTE in orthopaedic trauma patients, current guidelines recommend prescribing low-molecular-weight heparin (enoxaparin), although research in total joint arthroplasty suggests a potential benefit of aspirin as a less-expensive, widely available option.

Now, in a study likely to change the standard of care, aspirin has been found to be as effective as low-molecular-weight heparin in preventing VTE in patients undergoing surgery to repair bone fractures.

The findings were presented by the study’s principal investigator, Robert V. O’Toole, MD, at the 2022 annual meeting of the Orthopaedic Trauma Association in Tampa, Florida.

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“We expect our findings from this large-scale trial to have an important impact on clinical practice, and potentially even change the standard of care,” said Dr. O’Toole, the Hansjörg Wyss Medical Foundation Endowed Professor in Orthopaedic Trauma at the University of Maryland School of Medicine and head of the school’s Division of Orthopaedic Traumatology.

“Orthopaedic trauma patients are commonly prescribed the blood thinner low-molecular-weight heparin to prevent blood clots for weeks following surgery. Not only does the medication need to be injected, but it can also be quite expensive compared to aspirin.”

Study Methodology and Findings

Called PREVENTion of CLots in Orthopaedic Trauma, or PREVENT CLOT, the multi-center randomized clinical trial was conducted at 21 trauma centers in the US and 2 Canada. The researchers enrolled 12,211 patients with upper or lower extremity fractures necessitating surgery or any fracture of the pelvis or acetabulum regardless of the specific treatment, making it the largest-ever trial in orthopaedic trauma patients.

Patient enrollment began in April 2017 and continued through 2021. The patients were randomly assigned to receive either 30 mg of injectable low-molecular-weight heparin twice daily or 81 mg of aspirin twice daily. They were followed for 90 days after surgery.

The primary outcome measure was all-cause mortality, with secondary outcome measures of:

• Cause-specific death
• Non-fatal pulmonary embolism
• Deep vein thrombosis
• Bleeding complication
• Wound complication
• Deep surgical site infection

The researchers found that aspirin was non-inferior to low-molecular-weight heparin in preventing death from any cause: 47 patients in the aspirin group died compared with 45 patients in the heparin group.

No differences were found between groups for non-fatal pulmonary embolism, bleeding complications, or all other safety outcomes.

Of all outcomes studied, only 1 potential difference was noted: Patients in the low-molecular-weight heparin group had fewer blood clots in their legs than patients in the aspirin group. This relatively small difference was driven by clots lower in the leg, which are of unclear clinical importance.

Sources

O’Toole R, and the Major Extremity Trauma Research Consortium (METRC) Investigators. PREVENT CLOT (Aspirin Versus Low-Molecular-Weight Heparin for Thromboprophylaxis): A Randomized Clinical Trial of Over 12,000 Orthopaedic Trauma Patients. Presented at the 2022 annual meeting of the Orthopaedic Trauma Association, October 12-15, Tampa, Florida.

O’Toole RV. Stein DM, Frey KP, et al. PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT): a randomised pragmatic trial protocol comparing aspirin versus low-molecular-weight heparin for blood clot prevention in orthopaedic trauma patients. BMJ Open. 2021 Mar 24;11(3):e041845. doi: 10.1136/bmjopen-2020-041845.

PREVENTion of Clot in Orthopaedic Trauma (PREVENT CLOT). ClinicalTrials.gov Identifier: NCT02984384.