How Does Aspirin Compare with Factor Xa Inhibitors for VTE Prophylaxis?

    Dr. Emanuele Chisari and Dr. Javad Parvizi answer ICJR’s questions about their study on 90-day outcomes in total joint arthroplasty patients who received either a factor Xa inhibitor or aspirin to prevent post-surgery venous thromboembolism.

    ICJR: What question did you and your co-authors want to answer with this study? 

    Emanuele Chisari, MD: Chemoprophylaxis for venous thromboembolism (VTE) following primary or revision total joint arthroplasty (TJA) requires a balance: A potent anticoagulant or antiplatelet drug – a factor Xa inhibitor, for example – can cause serious side effects such as bleeding, while a less-aggressive drug – aspirin, for example – might increase the patient’s chances of developing VTE.

    Given the lack of consensus on which chemoprophylactic agent is preferred, we wanted to determine if there are any differences in short-term outcomes and readmissions when comparing TJA patients discharged on a factor Xa inhibitor versus aspirin. 

    RELATED: Is Aspirin an Effective Way to Prevent VTE in Hip Fracture Patients?

    ICJR: What did you conclude? 

    Dr. Chisari: As expected, patients who were prescribed an Xa inhibitor had higher rates of atrial fibrillation and comorbidities than patients who were prescribed aspirin. Despite this difference in comorbid conditions, both groups had low rates of deep VTE: 0.4% for aspirin and 0.62% for factor Xa inhibitors.

    In addition, we observed no difference in overall 90-day readmission rates (2.19% for aspirin vs 2.18% for factor Xa inhibitors; P=1.00) or emergency department visits (7.66% for aspirin vs 5.95% for factor Xa inhibitors; P=0.147). No clinically significant difference in reason for readmission was observed.

    We found that in our study population, aspirin was as effective as factor Xa inhibitors in preventing VTE following TJA. Some patients may need the more-potent drug, however, due to their comorbid conditions. More studies are needed to further clarify this issue.

    ICJR: How did you reach your conclusions? What was your study cohort and what did you find with your analysis? 

    Dr. Chisari: This was a retrospective, single-center study that included 5407 patients who had undergone primary or revision TJA between 2015 and 2018. Patients were excluded if they had fewer than 3 months of follow-up or were discharged on VTE chemoprophylaxis other than 81 mg of aspirin, 2.5 mg of apixaban (Eliquis), or 10 mg of rivaroxaban (Xarelto). After these exclusions, we had 604 patients who were discharged with a factor Xa inhibitor and 2017 who were discharged with aspirin.

    A 3:1 propensity score match between aspirin and factor Xa inhibitor was performed using age, gender, and BMI to control for patient demographics. In addition, we recorded reasons for readmission or visits to the emergency department or urgent care center, focusing on wound complications, infection, fracture, and dislocation.

    As mentioned above, patients discharged with a factor Xa inhibitor were more likely than patients discharged with aspirin to have serious comorbidities, including history of VTE (P<0.001), congestive heart failure (P=0.003), irregular heart rhythm such as atrial fibrillation (P<0.001), and stroke (P=0.002).

    RELATED: Another Use for Aspirin after TKA: Treatment of Infrapopliteal DVT

    ICJR: Why are these findings significant for clinical practice? 

    Javad Parvizi, MD, FRCS: We observed no difference in thromboembolic events, readmissions, emergency department or urgent care visits, or overall complications in the factor Xa inhibitor group versus the aspirin group when examining 90-day outcomes, despite definite differences in comorbid conditions. Patients who were prescribed a factor Xa inhibitor were more likely to have a past medical history of a thrombotic event or congestive heart failure; however, no appreciable differences in postoperative thromboembolic events, bleeding, or other complications were observed.

    Our study, therefore, provides additional evidence that aspirin is an effective drug for chemoprophylaxis of VTE in most patients who have undergone primary and revision TJA. Surgeons can feel comfortable prescribing aspirin, although we caution that a careful history is needed to determine if a factor Xa inhibitor would be a better choice, as described above. Additional studies are needed to further define the population that would most benefit from a factor Xa inhibitor to avoid over-prescribing these drugs and unnecessarily putting patients at risk for serious side effects.

    About the Experts

    Emanuele Chisari, MD, is a Research Fellow at The Rothman Orthopaedic Institute, Philadelphia, Pennsylvania, and a PhD student at the University of Oxford in the United Kingdom.

    Javad Parvizi, MD, FRCSC, is an orthopaedic surgeon and the Director of Clinical Research at The Rothman Orthopaedic Institute. He is also the James Edwards Professor Chair of Orthopaedics at Thomas Jefferson University, Philadelphia, Pennsylvania.

    Disclosures: Dr. Chisari and Dr. Parvizi have no disclosures relevant to this article.


    Van Nest DS, Chisari E, Clarkson S, Klein GR, Parvizi J. Factor Xa inhibitors vs. aspirin for venous thromboembolism prophylaxis: comparing 90-day complications and readmissions in patients undergoing total joint arthroplasty (Paper 111). Presented at the 2021 Annual Meeting of the American Academy of Orthopaedic Surgeons, August 31-September 3, San Diego, California.

    Aspirin photo by Sauligno, from Wikipedia.com, provided under an Attribution-ShareAlike 3.0 Unported (CC BY-SA 3.0) license. Photo was cropped.