Aspirin is good enough for VTE prevention after knee replacement


 Aspirin is good enough for VTE 
prevention after knee replacement

Registry analysis shows aspirin
not inferior to other anticoagulants

By Ashley Lyles*

Aspirin was at least as good for preventing venous thromboembolism (VTE) after total knee replacement surgery as anticoagulant drugs such as warfarin, low molecular weight heparin, and the newer oral medications, according to a large retrospective analysis.

Among more than 40,000 patients in a statewide arthroplasty registry from 2013 to 2015, unadjusted rates of a composite VTE outcome were 1.16% for those receiving prophylaxis with aspirin alone, versus 1.42% for those receiving only other antithrombotic agents and 1.31% in those receiving a combination of aspirin and other drugs, reported Brian Hallstrom, MD, of University of Michigan Health System in Ann Arbor, and colleagues in JAMA Surgery.

In comparison to patients receiving other chemoprophylaxis, the composite VTE outcome for aspirin alone was non-inferior (adjusted OR 0.85; 95% CI 0.68-1.07,  P=0.007 for inferiority).

Unadjusted rates of individual adverse outcomes were also numerically lower with aspirin:

  • Death: 0.10% with aspirin alone, 0.12% for anticoagulants alone
  • Pulmonary embolism: 0.32% with aspirin alone, 0.39% with anticoagulants alone
  • Deep vein thrombosis: 0.74% with aspirin alone, 0.90% with anticoagulants alone
  • Bleeding: 0.90% with aspirin alone, 1.14% with anticoagulants alone

After adjustments for patient factors, aspirin easily met the pre-specified criteria for non-inferiority relative to anticoagulants. The study noted that use of aspirin alone for post-surgical VTE prophylaxis rose markedly during the study period, from 10% to about 50% of procedures, whereas anticoagulants declined commensurately in popularity.

Yet the evidence base for this change in practice has been weak, Hallstrom and coauthors noted. Prior findings were of low quality; the previous studies evaluated cases with asymptomatic deep venous thromboembolism, and underrepresented the risk of bleeding at the surgical site and the risk of reoperation following total knee arthroplasty (TKA), leading to concern surrounding publication bias in support of anticoagulant prophylaxis for VTE. Furthermore, over the last 10 years, total knee replacement surgery has changed, "resulting in a reduced VTE risk not accounted for in the current guidelines," the researchers emphasized.

The aim of this paper was "to determine whether aspirin as a single agent is inferior to other anticoagulation agents for reducing the risk of VTE or major bleeding events after unilateral primary TKA," they continued. Despite the rise in aspirin use for VTE prophylaxis following TKA over the last decade, "surgeons remain concerned about the safety and efficacy of this approach because of the limitations in studies supporting it," noted Robert Sterling, MD, and Elliot Haut, MD, PhD, both of Johns Hopkins University School of Medicine in Baltimore in an accompanying editorial.

This study "corresponds to several other reports regarding the effectiveness of aspirin compared to other modalities for VTE prevention," commented Joseph Bosco, MD, of New York University Langone Health in New York City, who was not involved in the study. Clinicians still need to figure out whether or not patients have other risk factors, like obesity, active cancer, smoking, use of oral contraceptives, and previous history of blood clots, which might contribute to VTE after surgery, emphasized Bosco to MedPage Today. "Patients with any of these risk factors probably should receive higher intensity chemoprophylaxis other than aspirin. Fortunately the majority of patients do not have these risk factors and can be safely prophylaxed with aspirin alone," Bosco continued.

Hallstrom's group analyzed data on 41,537 patients included in the Michigan Arthroplasty Registry Collaborative Quality Initiative, of whom 36% were men and the mean age was 66. These patients underwent total knee replacement at 29 member hospitals, with outcomes tracked over the course of 90 days following surgery.

While the study was not a prospective trial, Bosco said the results are nevertheless informative. "These registries leverage the power of large sample sizes to accurately determine the effectiveness or lack of effectiveness of clinical interventions," he said. "They are the future of population-based outcomes research and the data derived from these databases will inform future clinical decision making. The ultimate outcome is that our patients will receive more effective, safer care."

The study was limited by potential selection bias and residual confounding, noted the editorialists. Other limitations include that there's no indication of how pharmacologic prophylaxis was selected, and several potential confounders affecting the selection were not part of the propensity matching score because they were not tracked in the registry, Sterling and Haut emphasized.

Further granular and nuanced risk stratification might help surgeons in their VTE prophylaxis selection, the editorialists noted. "The question remains unanswered of which specific selection criteria should be used to determine a recommendation for an exact pharmacologic agent, and generalizing to all patients would be inappropriate based on this study," Sterling and Haut wrote.

Sterling and Haut offered another note of caution: although the paper "adds to the ongoing list of retrospective studies supporting the use of aspirin in selected patients who had undergone TKA, the story is far from over."

Ref:  Hood B et al "Association of aspirin with prevention of venous thromboembolism in patients after total knee arthroplasty compared with other anticoagulants a non-inferiority analysis" JAMA Surg 2018; DOI: 10.1001/jamasurg.2018.3858.

* Staff Writer, MedPage Today October 18, 2018.

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