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The representativeness of direct oral anticoagulant clinical trials to hospitalized patients with atrial fibrillation

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Abstract

Purpose

Trials of the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban and apixaban provide the basis for prescribing for the prevention of stroke and systemic embolism in atrial fibrillation (AF). The objective of this study was to assess the representativeness of the three pivotal DOAC randomized controlled trials of dabigatran, rivaroxaban and apixaban for unselected hospitalized patients with AF.

Methods

A cross-sectional study was undertaken. All patients discharged with AF between 2012 and 2015 from a large public hospital network in Melbourne, Australia, were identified. Inclusion and exclusion criteria from the DOAC trials were applied. The proportions of hospitalized patients with AF who would have been eligible for the dabigatran (RE-LY), rivaroxaban (ROCKET-AF) and apixaban (ARISTOTLE) trials were estimated, as was pooled eligibility for all three trials. Characteristics of eligible and ineligible patients were compared.

Results

For the 4734 patients, application of the inclusion and exclusion criteria resulted in 60.5, 52.6 and 35.8% eligibility for the trials of apixaban, dabigatran and rivaroxaban, respectively. Pooled eligibility across all three trials demonstrated that 33.4% of the patients would have been eligible for all three trials but 36.7% ineligible for any trial. Ineligible patients who met exclusion criteria were older and experienced more comorbidities.

Conclusions

The apixaban and dabigatran trials may be the most representative of hospitalized patients with AF. The DOAC trial results can readily be extrapolated to, and guide prescribing for, at least two thirds of patients discharged from a large metropolitan health service in Australia.

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Acknowledgements

This work was supported by a grant from the Victorian Department of Health and Human Services, Clinical Leadership Group for the Care of Older People in Hospital and a Joint Medicine-Pharmacy Monash Strategic Grant. LF is supported by a Research Training Scheme PhD Scholarship from the Australian Government: Department of Education and Training. JI is supported by the National Health and Medical Research Council’s Early Career Fellowship.

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Authors and Affiliations

  1. Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia

    Laura Fanning & Pēteris Dārziņš

  2. Geriatric Medicine, Eastern Health, Melbourne, Australia

    Laura Fanning & Pēteris Dārziņš

  3. Pharmacy Department, Eastern Health, Melbourne, Australia

    Laura Fanning

  4. Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia

    Jenni Ilomäki & J. Simon Bell

  5. School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

    Jenni Ilomäki

Authors
  1. Laura Fanning
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  2. Jenni Ilomäki
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  3. J. Simon Bell
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  4. Pēteris Dārziņš
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Contributions

All authors contributed to the concept and design. LF performed data analysis. LF performed drafting of the manuscript. All authors contributed to the interpretation of the data, manuscript revisions and read and approved the final manuscript. LF takes responsibility for the integrity of the data analysis.

Corresponding author

Correspondence to Pēteris Dārziņš.

Ethics declarations

Approval for the study was obtained from both hospital and university Human Research Ethics Committees (ethics approval numbers LR2015-64 and CF16/1211).

Conflict of interest

The authors declare that they have no conflicts of interest.

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Fanning, L., Ilomäki, J., Bell, J.S. et al. The representativeness of direct oral anticoagulant clinical trials to hospitalized patients with atrial fibrillation. Eur J Clin Pharmacol 73, 1427–1436 (2017). https://doi.org/10.1007/s00228-017-2297-0

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  • DOI: https://doi.org/10.1007/s00228-017-2297-0

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