Thromboprophylaxis after Extremity Fracture — Time for Aspirin?
Matthew Costa
N Engl J Med 2023; 388:274-275
DOI: 10.1056/NEJMe2214045
Hospital-acquired venous thromboembolism remains a common and preventable cause of death, so many health care systems around the world mandate that all patients who are admitted to the hospital undergo a risk assessment for venous thromboembolism.1,2 Patients who have had traumatic injuries are at particular risk for venous thromboembolism as a result of their injuries, the surgeries that are often performed to treat their broken bones, and the patients’ relative immobility during recovery.3 Therefore, nearly all patients who undergo surgery for a fracture are considered to be at high risk for venous thromboembolism, and preventative interventions are recommended.
Interventions to reduce the risk of venous thromboembolism in patients who have undergone surgery for fractures fall into two broad categories. The first is mechanical prophylaxis (e.g., antiembolism stockings that compress the legs to reduce pooling of venous blood in the lower limbs and intermittent pneumatic compression devices that actively squeeze the muscles in the foot or leg to keep blood moving in the veins). However, since the legs are commonly involved in traumatic injuries, mechanical devices may be difficult or impossible to apply in this group of patients. The other category of prophylaxis is pharmacologic, which includes oral drugs (e.g., aspirin and direct oral anticoagulants) and injectable low-molecular-weight heparin.
The choice of agent for pharmacologic prophylaxis is made on the basis of balancing the effectiveness of the therapy with regard to reducing venous thromboembolism and the risk of side effects, most notably bleeding.4 In many countries, low-molecular-weight heparin that is delivered by subcutaneous injection has become the pharmacologic prophylaxis of choice for patients who have undergone surgery for a traumatic injury because it is considered to be effective and to have a low risk of bleeding complications.1,5 However, patients generally do not like receiving the injections, which are painful and often cause bruising at the site of injection, leading to concerns about adherence.6 As the number of patients who are assessed to be at risk for venous thromboembolism increases, more patients will be treated with pharmacologic prophylaxis, leading to an increase in health care costs.7 This leads to the question: what type of pharmacologic prophylaxis should clinicians and health care systems recommend?
In this issue of the Journal, investigators in the Major Extremity Trauma Research Consortium8 go a long way toward answering this question. In this trial, 12,211 participants 18 years of age or older with an operatively treated limb fracture or any pelvic or acetabular fracture were randomly assigned to receive low-molecular-weight heparin at a dose of 30 mg twice daily by injection or aspirin at a dose of 81 mg taken orally twice daily. The main finding of the trial was that the occurrence of death from any cause at 90 days was very similar in the two groups: 0.78% of patients in the aspirin group and 0.73% in the heparin group. The authors concluded that aspirin was noninferior to low-molecular-weight heparin in preventing death in the trial population.
Although this is not the first trial to address the choice of aspirin or heparin for venous thromboembolism prophylaxis among patients with operatively treated extremity fractures (or any pelvic or acetabular fracture), this is by far the largest trial to date and provides compelling evidence that a readily available, inexpensive drug, taken orally, is a viable alternative to an injectable pharmacologic prophylaxis.
Are there any caveats to this message? The trial shows several secondary outcomes that support the main conclusion of the trial, including a similar risk of pulmonary embolism in the two groups and, in terms of safety outcomes, no evidence of a difference in the incidence of bleeding events, which occurred in 13.72% of patients in the aspirin group and 14.27% in the low-molecular-weight–heparin group. However, in keeping with previous trials, the authors noted that deep-vein thrombosis was more frequent in patients who had received aspirin than in those who had received heparin (2.51% vs. 1.71%), although the absolute difference was small (0.80 percentage points). Although deep-vein thrombosis is clearly not as serious as a fatal pulmonary embolism, it is not an inconsequential problem. Post-thrombotic syndrome affects some people who have had a deep-vein thrombosis of the leg, and this condition can cause chronic pain and swelling.9
The findings in this trial clearly indicate that guidelines for the prevention of hospital-acquired venous thromboembolism will need to be rewritten to include the option of aspirin in patients with traumatic injuries. More work is needed to determine whether aspirin should also be considered for venous thromboembolism prophylaxis after other types of surgeries and for nonsurgical patients who have risk factors for venous thromboembolism.
