Aspirin alone may be sufficient to balance the risks of venous thromboembolism (VTE) and bleeding following total knee replacement surgery, according to a study published online in JAMA Surgery.
The retrospective analysis included 41,537 patients who underwent total knee arthroplasty at one of 29 hospitals in Michigan. Researchers led by Brandon R. Hood, MD, with the University of Michigan, sought to compare the rates of bleeding and a composite of VTE events (pulmonary embolism, deep vein thrombosis or death) based on which anticoagulants patients received, if any.
“While nearly all orthopedic surgeons agree that pharmacologic prophylaxis is the standard of care, major disagreements remain about the optimal, or even acceptable, medication regimens,” wrote Robert S. Sterling, MD, and Elliott R. Haut, MD, PhD—both with Johns Hopkins University School of Medicine—in an accompanying editorial. “Even evidence-based guidelines from different national societies, using the same published literature, often make different recommendations.”
Aspirin monotherapy was used in 30.9 percent of patients in the study, while 54.5 percent were treated with another type of anticoagulant, 1.6 percent received no drug prophylaxis and 13 percent received both aspirin and another anticoagulant. Other anticoagulants were categorized as one group and included agents such as factor Xa inhibitors, warfarin and low-molecular-weight heparin (LMWH).
The 90-day primary outcome of VTE occurred in:
- 1.16 percent of patients taking aspirin only
- 1.42 percent of patients taking another anticoagulant only
- 1.31 percent of patients taking aspirin plus another anticoagulant
- 4.79 percent of patients with no pharmacotherapy
Similarly, the rates of major bleeding at 90 days were lowest for those taking aspirin alone (0.90 percent), followed by anticoagulation alone (1.14 percent), a combination of the two therapies (1.35 percent) and no drug prophylaxis (1.50 percent).
Aspirin easily cleared the bar of noninferiority for which the study was powered, demonstrating relative risk reductions of 15 percent for VTE and 20 percent for bleeding events compared to other drug-based therapies.
“There are several reasons to prefer using aspirin for VTE prophylaxis in the appropriately screened patient,” Hood and colleagues wrote. “Aspirin administration is simple, safe, and does not require monitoring. Although this study did not find a significant difference, a 2008 practice survey conducted by the American Association of Hip and Knee Surgeons found that while most orthopedic surgeons felt LMWH to be most efficacious, aspirin was felt to be the easiest to use with the lowest risk of bleeding or wound complications.”
The researchers also pointed out that aspirin is the most affordable of the anticoagulant options, with a price tag of around $2 per month.
“The reported cost for a 30-day supply of rivaroxaban is approximately $379 to $450, and that of LMWH is estimated at $450 to $890,” they wrote. “Warfarin costs a few dollars for a 30-day course, but with monitoring considered, the cost approaches that of the other anticoagulants. … These cost differences could have a substantial association with a patient’s out-of-pocket expenses as well as the cost of a hospital’s overall bundle in the new episode payment models.”
The authors acknowledged they didn’t examine event rates for specific medications included in the anticoagulant category due to the “numerous combinations” of drugs that were employed. Also, they didn’t have data on why no medications were prescribed in some cases, and added that their registry may not be generalizable to all health systems given that it contained results from “an active, collaborative, quality improvement environment with motivated participants.”
“While this observational study supports the use of aspirin, clinical judgment is still required for the ultimate selection of prophylaxis,” Hood et al. wrote. “In addition, only the pharmacologic prophylaxis was studied. This is just 1 component of a modern protocol that should also include regional anesthesia, comprehensive pain management protocols, intermittent pneumatic compression devices, tranexamic acid, and early mobilization.”
Sterling and Haut said it would be useful to have more specific criteria or risk scores to help match certain patients to an exact drug—evidence that’s difficult to build without prospective trials. To that end, they noted the PEPPER trial could provide crucial insight. It is currently enrolling approximately 25,000 hip and knee replacement patients and is expected to be completed by February 2021.
“This large, multicenter, randomized clinical trial comparing low-dose aspirin with warfarin and rivaroxaban will provide evidence for surgeons and patients to choose an ideal pharmacologic agent for VTE prophylaxis after joint replacement,” Sterling and Haut wrote. “The answer cannot come soon enough.”