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Appropriateness of initial dose of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation in the UK
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  • Published on:
    Response to Letter by Pollock et al on “Appropriateness of initial dose of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation in the UK”
    • Luis A García Rodríguez, Director Spanish Centre for Pharmacoepidemiologic Research (Madrid, Spain)
    • Other Contributors:
      • Mar Martín-Pérez, Doctor
      • Pareen Vora, Epidemiologist
      • Luke Roberts, Study Medical Expert
      • Yanina Balabanova, Epidemiology
      • Gunnar Brobert, Epidemiologist
      • Samuel Fatoba, Study Medical Expert
      • Kiliana Suzart-Woischnik, Epidemiology
      • Bernhard Schaefer, Epidemiology
      • Ana Ruigómez, Doctor

    We thank Dr Pollock and colleagues for their interest in our recent study, which suggested that among patients with non-valvular atrial fibrillation in the UK, inappropriate underdosing was more than twice as common among patients starting on apixaban than those starting on dabigatran or rivaroxaban.

    In our analyses, we assumed that patients with missing data on renal function were likely to have unimpaired renal function. Pollock et al expressed their concern regarding the possibility of significant bias resulting from misclassification of renal function among these patients, which could have resulted in the percentage of patients inappropriately prescribed a reduced dose NOAC being overestimated. Among our study population of 30,467 patients, 3856 (12.7%) had missing data on renal function (eGFR values).

    Pollock and colleagues also queried the absence of bodyweight data in our results. We acknowledge that it may have been useful for the reader to see these data, although we presented data on BMI in Table 1 of our article as a proxy measure. Nevertheless, we can confirm that in our dataset very few patients had missing data on bodyweight (2.6% of patients starting on apixaban, 3.0% of those starting on dabigatran and 2.3% of those starting on rivaroxaban). Among patients with a recorded bodyweight, the mean bodyweight was 81.4 kg for patients starting on apixaban, 82.6 kg for those starting on dabigatran, and 82.0 kg for those starting on rivaroxaban. While...

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    Conflict of Interest:
    PV, YB, KS-W and BS are employees of Bayer AG (Germany), the funder of the study; GB is an employee of Bayer AB, (Stockholm, Sweden); LR and SF are employees of Bayer PLC (Reading, UK). KS-W declares Bayer stocks; LR and SF declare shares in Bayer. LAGR, MM-P and AR work for the Spanish Centre for Pharmacoepidemiologic Research (Madrid, Spain), which has received research funding from Bayer AG. LAGR also declares honoraria for serving on advisory boards for Bayer AG.
  • Published on:
    Response to Garcia Rodriguez study, September 2019
    • Kevin G Pollock, Outcomes Research Scientist Bristol-Myers Squibb Pharmaceuticals Ltd
    • Other Contributors:
      • Steven P Lister, Senior Health Economist
      • Alexander T Cohen, Consultant Physician and Epidemiologist
      • Zahra Chambers, Medical Affairs Adviser
      • Robert Trotter, Senior Medical Affairs Adviser

    We read with interest the recent article by Garcia Rodriguez et al. (2019) [1] “Appropriateness of initial dose of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation in the UK”. We have concerns that there are significant methodological flaws with the study. Consequently, we suggest that the inferences raised in the Discussion with respect to dosing of apixaban are speculative and the conclusions are not based on a considered evaluation of evidence.

    Bias resulting from misclassification of renal function
    In the study by Rodriguez, the authors state, “For each NOAC cohort, we calculated the percentage of patients appropriately dosed, both overall and according to whether the daily dose of the index NOAC was a standard or reduced dose. For this calculation, patients with missing data on renal function were assumed to have normal renal function.” To assume a ‘missing’ value as ‘normal’ is scientifically unsound, leading to significant misclassification bias which is likely to over-estimate the proportion of patients inappropriately prescribed the lower dose. It is important to note that the level of renal function recording in the THIN and CPRD databases is sub-optimal [3, 4]. We suggest that it would have been methodologically apposite to define the proportion of patients where renal function was unknown and perform a ‘known parameters’ analysis to validate the assumption and extrapolation to the total population....

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    Conflict of Interest:
    KGP, SPL, and ZC are employees of BMS Pharmaceuticals Ltd. ATC reports honoraria from Bristol-Myers Squibb Company during the conduct of the study; RT is an employee of Pfizer UK.