Article Text

Download PDFPDF

Real-world adherence to oral anticoagulants in atrial fibrillation patients: a study protocol for a systematic review and meta-analysis
  1. Clara L Rodríguez-Bernal1,2,
  2. Aníbal García-Sempere1,2,
  3. Isabel Hurtado1,2,
  4. Yared Santa-Ana1,2,
  5. Salvador Peiró1,2,
  6. Gabriel Sanfélix-Gimeno1,2
  1. 1 Health Services Research Unit, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Valencia, Spain
  2. 2 Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Valencia, Spain
  1. Correspondence to Mr Aníbal García-Sempere; garcia_ani{at}


Introduction Atrial fibrillation (AF) is one of the leading causes of cerebrovascular mortality and morbidity. Oral anticoagulants (OACs) have been shown to reduce the incidence of cardioembolic stroke in patients with AF, adherence to treatment being an essential element for their effectiveness. Since the release of the first non-vitamin K antagonist oral anticoagulant, several observational studies have been carried out to estimate OAC adherence in the real world using pharmacy claim databases or AF registers. This systematic review aims to describe secondary adherence to OACs, to compare adherence between OACs and to analyse potential biases in OAC secondary adherence studies using databases.

Methods and analysis We searched on PubMed, SCOPUS and Web of Science databases (completed in 26 September 2018) to identify longitudinal observational studies reporting days’ supply adherence measures with OAC in patients with AF from refill databases or AF registers. The main study endpoint will be the percentage of patients exceeding the 80% threshold in proportion of days covered or the medication possession ratio. Two reviewers will independently screen potential studies and will extract data in a structured format. A random-effects meta-analysis will be carried out to pool study estimates. The risk of bias will be assessed using the Newcastle-Ottawa Scale for observational studies and we will also assess some study characteristics that could affect days’ supply adherence estimates.

Ethics and dissemination This systematic review using published aggregated data does not require ethics approval according to Spanish law and international regulations. The final results will be published in a peer-review journal and different social stakeholders, non-academic audiences and patients will be incorporated into the diffusion activities.

PROSPERO registration number CRD42018095646.

  • anticoagulation
  • statistics and research methods
  • clinical pharmacology
  • stroke
  • cardiology
  • quality in health care

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

Statistics from


  • Patient consent for publication Not required.

  • Contributors CLR-B, AG-S, SP and GS-G conceived the study. The protocol manuscript was drafted by CLR-B, SP and AG-S, and revised by all authors. CLR-B designed the search strategies and SP and AG-S will perform the search. CLR-B, AG-S, SP and IH will screen studies for inclusion, extract data and assess the risk of bias of included studies. GS-G will arbitrate disagreements between reviewers. CLR-B, AG-S, SP and YS-A will analyse and interpret the data. All authors have provided conceptual and/or methodological expertise. All authors have contributed to the critical revision of this manuscript for important intellectual content. All authors agree to be accountable for all aspects of the work and have read and approved the final manuscript.

  • Funding CLR-B and YS-A are partially funded by the Instituto de Salud Carlos III, Spanish Ministry of Economy, Industry and Competitiveness (grant number RD16/0001/0011 cofinanced by the European Regional Development Fund).

  • Disclaimer The views presented here are those of the authors and not necessarily those of the FISABIO Foundation, the Valencia Ministry of Health or any other institution.

  • Competing interests The FISABIO foundation (a non-for-profit research institution depending on the Valencia Ministry of Health) had a Collaboration Agreement with Boehringer Ingelheim to conduct non-conditioned independent research in chronic health care, pharmacoepidemiology and medical practice variation (2013–2014), and received an unrestricted research grant from Daiichi-Sankyo (2017), both not related with the current study. None of the mentioned institutions/firms played any role in this study.

  • Ethics approval This systematic review uses published studies as sources of data and did not include individual patients as study participants, nor individual patient data. Therefore, it does not require Ethics Research Committee approval according to Spanish law and international regulations.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.