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Clinical trials with direct oral anticoagulants for stroke prevention in atrial fibrillation: how representative are they for real life patients?

  • Pharmacoepidemiology and Prescription
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Abstract

Purpose

To identify the proportion of real-life patients with atrial fibrillation (AF) eligible for direct oral anticoagulant (DOAC) therapy, based on the inclusion and exclusion criteria used in the clinical studies and based on the officially approved indications as mentioned in the Summary of Product Characteristics (SmPC).

Methods

Data for this retrospective cross-sectional study was extracted from the UZ Brussel Stroke Registry, containing anonymized data of 2205 patients with a suspected stroke. Characteristics of patients with documented AF were compared with the patient characteristics in clinical trials and the approved indications in the SmPC.

Results

Data of 468 patients with AF was analyzed. Based on the selection criteria of the clinical trials, significantly less patients were eligible for treatment with rivaroxaban compared to dabigatran etexilate (39.3 versus 47.6 %; p = 0.010), but not compared to apixaban (45.5 %; p = 0.055). Based on the indications and contraindications in the SmPC, significantly fewer patients were eligible for apixaban compared to dabigatran etexilate and rivaroxaban (62.0 % for apixaban, 72.9 % for dabigatran etexilate, and 75.6 % for rivaroxaban; p < 0.001 and p < 0.001, respectively). Significantly, more patients were eligible for DOAC therapy based on the indications and contraindications in the SmPC compared to the inclusion and exclusion criteria of the clinical trials (72.9 versus 47.6 %; p < 0.001 for dabigatran; 75.6 versus 39.3 %; p < 0.001 for rivaroxaban and 62.0 versus 45.5 %; p < 0.001 for apixaban).

Conclusion

When taking into account the selection criteria from the pivotal clinical trials with DOACs for stroke prevention in AF, less than half of real-life patients are eligible for therapy with one of the DOACs. However, the indications mentioned in the SmPCs of these drugs are less strict.

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Authors and Affiliations

  1. Research group Clinical Pharmacology and Clinical Pharmacy (KFAR), Centre for Pharmaceutical Research (CePhar), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium

    S. Desmaele, S. Steurbaut, P. Cornu & A. G. Dupont

  2. Department of Neurology, Universitair Ziekenhuis Brussel (UZB) and Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium

    R. Brouns

Authors
  1. S. Desmaele
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  2. S. Steurbaut
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  3. P. Cornu
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  4. R. Brouns
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Correspondence to S. Desmaele.

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This work was supported in part by an unrestricted grant by Bayer NV-SA

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Authors’ Contributions

S. Desmaele contributed to the design of the study, the analysis and interpretation of the data, and drafted the manuscript. S. Steurbaut, P. Cornu, and A.G. Dupont contributed to the design of the study and the interpretation of the data. They all critically revised the manuscript. R. Brouns contributed to the data acquisition, to the interpretation of the data and critically revised the manuscript. All co-authors gave final approval to submit the manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Appendices

Appendix 1

Table 4 In- and exclusion criteria of the clinical trials
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Appendix 2

Table 5 Indications and contraindications as mentioned in the SmPC
Full size table

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Desmaele, S., Steurbaut, S., Cornu, P. et al. Clinical trials with direct oral anticoagulants for stroke prevention in atrial fibrillation: how representative are they for real life patients?. Eur J Clin Pharmacol 72, 1125–1134 (2016). https://doi.org/10.1007/s00228-016-2078-1

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  • DOI: https://doi.org/10.1007/s00228-016-2078-1

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