Aspirin = LMWH for Preventing Death After Fracture: Big RCT

A major RCT finds aspirin worked as well as LMWH in patients with fractures

What’s the Claim?

An enormous (>12,000 patients) multicenter RCT found that patients with fractures did just as well with aspirin as with low-molecular-weight heparin in terms of the risk of death or pulmonary embolism. LMWH was slightly (a fraction of a percentage point) better than aspirin in terms of preventing DVT.

How’s It Stack Up?

CORRelations’ Fracture & Trauma advisor calls this trial “a biggie,” and it is. It’s the largest trial on this topic, which is about as important as a topic can be, and the study was very well designed and executed. Before this RCT, smaller studies and pronouncements from the Trauma Quality Improvement Project (TQIP) seemed to be leaning the other way — in favor of stronger chemical anticoagulants in patients with fractures having surgery. It’s clear enough from prior research (and common sense) that patients would prefer aspirin to LMWH if they are comparably effective. This study, which used a robust noninferiority analysis, suggests this is true, at least for those who were enrolled — patients with lower extremity fractures proximal to the midfoot and upper extremity fractures from the shoulder to the wrist treated surgically, and those with pelvic or acetabular fractures regardless of whether they were treated surgically. It would’ve been nice to see subgroup analyses; a complicated subtrochanteric femur fracture surely is different from a distal radius fracture for the risk of clotting and death, but you can’t have it all.

What’s Our Take?

This RCT confronts what many surgeons consider to be the most important issue in the thromboprophylaxis conversation — the idea that the goal is not to prevent clots, but to prevent serious complications after trauma (like bleeds, clinically important clots, and deaths). The fact that many secondary findings in the trial — that is, outcomes other than death — generally supported the main discovery of no-difference in any of the big complications between aspirin and an expensive injectable drug further reassures us that the finding is trustworthy and actionable. A thoughtful commentary that accompanied this article suggested that guidelines should be rewritten based on results from the trial so as to include aspirin as an option. We agree, and we believe this is likely to occur.


Major Extremity Trauma Research Consortium (METRC); O'Toole RV, Stein DM, et al. Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis After a Fracture. N Engl J Med. 2023;388:203-213.