Frontiers in Pharmacology (Jul 2024)

How enoxaparin underdosing and sex contribute to achieving therapeutic anti-Xa levels

  • Alexander Tinchon,
  • Alexander Tinchon,
  • Alexander Tinchon,
  • Joana Brait,
  • Joana Brait,
  • Sascha Klee,
  • Uwe Graichen,
  • Christian Baumgartner,
  • Oliver Friedrich,
  • Elisabeth Freydl,
  • Elisabeth Freydl,
  • Elisabeth Freydl,
  • Stefan Oberndorfer,
  • Stefan Oberndorfer,
  • Stefan Oberndorfer,
  • Walter Struhal,
  • Walter Struhal,
  • Barbara Hain,
  • Barbara Hain,
  • Christoph Waiß,
  • Christoph Waiß,
  • Christoph Waiß,
  • Dagmar Stoiber

DOI
https://doi.org/10.3389/fphar.2024.1377232
Journal volume & issue
Vol. 15

Abstract

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IntroductionAnti-Xa serves as a clinical surrogate for assessing the efficacy and bleeding risk in patients treated with enoxaparin for thromboembolic events. Evidence from the literature and empirical observations suggest that patients are underdosed in clinical practice to avoid bleeding complications. This study aimed to investigate such underdosing of enoxaparin and its potential impact on achieving therapeutic anti-Xa levels.MethodsThis multicentric, retrospective, observational study included patients with acute ischemic stroke due to atrial fibrillation. All patients received enoxaparin in the therapeutic setting with subsequent anti-Xa measurements. The one-sample, one-tailed Wilcoxon signed-rank test was used to identify a significant difference between the doses administered and the recommended daily dose. Logistic regression model analysis was performed to identify additional predictors affecting achievement of the therapeutic anti-Xa target range. Stepwise forward-backward selection with Akaike’s information criterion as metric was applied to refine the logistic regression model.ResultsA total of 145 patients from the university hospitals of St. Pölten and Tulln in Lower Austria were included. The median daily enoxaparin dose administered was 1.23 mg/kg, resulting in an overall target range achievement rate of 66%. As compared to recommended therapeutic doses, significant underdosing of enoxaparin was evident in both participating centers (p < 0.001). The calculated threshold dose to achieve the therapeutic target range with a 90% probability was 1.5 mg/kg enoxaparin daily. Female sex was found to be a strong independent predictor of achieving a therapeutic target range (OR 9.44; 95% CI 3.40–30.05, p < 0.001).ConclusionDespite the underdosing observed in both centers, therapeutic anti-Xa levels were achieved with lower than recommended doses of enoxaparin, and women required even lower doses than men. These findings warrant further confirmation by prospective studies.

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