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Commentary on an article by Alexander J. Rondon, MD, MBA, et al.: “The Use of Aspirin for Prophylaxis Against Venous Thromboembolism Decreases Mortality Following Primary Total Joint Arthroplasty”

Herman, Amir MD, PhD

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The Journal of Bone and Joint Surgery: March 20, 2019 - Volume 101 - Issue 6 - p e25
doi: 10.2106/JBJS.18.01378
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Commentary

In their retrospective study, “The Use of Aspirin for Prophylaxis Against Venous Thromboembolism Decreases Mortality Following Primary Total Joint Arthroplasty,” Rondon et al. compared mortality rates of patients who received aspirin as prophylaxis against venous thromboembolism (VTE) with those of patients who received other prophylactic drugs, and found lower mortality rates among patients who received aspirin. The authors suggested the lower mortality rates were likely a result of the cardioprotective effects of the drug. The differences in mortality at 30 and 90 days, as well as at 1 year, were significant. Additionally, the rates of mortality due to VTE in the non-aspirin cohort were 0.02%, 0.02%, and 0.03% at 30 days, 90 days, and 1 year, respectively, whereas no patient in the aspirin cohort died as a result of VTE.

However, the study has several limitations. First, they group all types of non-aspirin prophylaxis medications. Specifically, they state that most patients in the non-aspirin cohort were given warfarin, which might cause bias and raises the question whether the actual comparison is between aspirin and warfarin. Second, it is a single-center study, which means it was influenced by institutional guidelines and practices. Specifically, the switch to the use of aspirin was made in more recent years, meaning the results might be confounded by recent introductions of rapid recovery and physiotherapy protocols, the use of different prostheses, and the use of newer surgical techniques at different time points. For example, patients who undergo direct anterior total hip replacements tend to recover faster than patients who undergo direct lateral (Hardinge) total hip replacements.

The authors have shown that postoperative aspirin use reduced the rate of mortality at 1 year, which seems somewhat counterintuitive as I believe the protective effect might actually be attributed to the fact that more patients in the aspirin cohort used aspirin preoperatively. Although analysis of preoperative aspirin use was part of the multivariate model, there might have been some confounding effect by the preoperative aspirin use that may have continued after surgery.

Finally, the authors utilized 3 multivariate logistic regression models, 1 for each of the 3 time points examined: 30 days, 90 days, and 1 year. When modeling regression survival data, it is common to use the Cox proportional hazards model and include the specific mortality time, not only the mortality rates at predetermined time points. The use of the Cox proportional hazards model might have avoided the finding that aspirin had a protective effect 30 days and 1 year after surgery, but only a statistical trend (p value = 0.067) at 90 days.

In conclusion, I think this is an important study that should be considered by surgeons when choosing prophylaxis against VTE following total joint replacement. The drawbacks mentioned here are inherent to a retrospective study. The evidence presented strengthens recent randomized controlled clinical trials that have shown comparable rates of VTE when comparing aspirin to other anticoagulants1,2. It should be noted, however, that it seems the number of patients necessary to show difference in mortality between 0.09% and 0.026% is tens of thousands, whereas most randomized controlled trials only include thousands of patients and thus will be underpowered to detect such a difference.

References

1. Anderson DR, Dunbar MJ, Bohm ER, Belzile E, Kahn SR, Zukor D, Fisher W, Gofton W, Gross P, Pelet S, Crowther M, MacDonald S, Kim P, Pleasance S, Davis N, Andreou P, Wells P, Kovacs M, Rodger MA, Ramsay T, Carrier M, Vendittoli PA. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial. Ann Intern Med. 2013 Jun 4;158(11):800-6.
2. Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707.

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