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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01353

Estimating adherence based on prescription or dispensation information: impact on thresholds and outcomes. A real-world study with atrial fibrillation patients treated with oral anticoagulants in Spain.

  • 1Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Spain

To estimate drug exposure, Proportion of Days Covered (PDC) and percentage of patients with PDC≥80% from a cohort of atrial fibrillation patients initiating oral anticoagulant (OAC) treatment. We employed three different approaches to estimate PDC, using either data from prescription and dispensing (PD cohort) or two common designs based on dispensing information only, requiring at least one (D1) or two (D2) refills for inclusion in the cohorts. Finally, we assessed the impact of adherence on health outcomes according to each method.

Population-based retrospective cohort of all patients with Non-Valvular Atrial Fibrillation, who were newly prescribed acenocoumarol, apixaban, dabigatran or rivaroxaban from Nov2011 to Dec2015 in the Valencia region (Spain). Patients were followed for 12 months to assess adherence using three different approaches (PD, D1 and D2 cohorts). To analyze the relationship between adherence (PDC≥80) assessed by different approaches and outcomes (death for any cause, stroke or bleeding) Cox regression models were used. For the identification of clinical events patients were followed from the end of the adherence assessment period to the end of the available follow-up period.

PD cohort included all patients with an OAC prescription (n=38,802), D1 cohort excluded fully non-adherent patients (n=265) and D2 cohort also excluded patients without two refills separated by 180 days (n=2,614). PDC≥80% ranged from 94% in the PD cohort to 75% in the D1 cohort. Drug exposure among adherent (PDC≥80%) and non-adherent (PDC<80%) patients was different between cohorts. In adjusted analysis, high adherence reduced the risk of death (Hazard Ratio (HR): from 0.82 to 0.86) and (except in the PD cohort) the risk for ischemic stroke (HR: from 0.61 to 0.64) without increasing the risk of bleeding.

Common approaches to assess adherence using a measures based on days’ supply exclude non-adherent patients and, also, misattribute periods of doctors’ discontinuation to patient non-adherence, misestimating adherence overall. Additionally, when using the PDC80 threshold, very different groups of patients may be classified as adherent or non-adherent depending on the method used for the calculation of adherence measures. High adherence and high exposure to OAC in NVAF patients was associated with better outcomes.

Keywords: Proportion of days covered (PDC), Medication Adherence, threshold, Oral anticoagulants (OACs), clinical outcomes, Real world evidence (RWE)

Received: 04 Aug 2018; Accepted: 05 Nov 2018.

Edited by:

Kurt E. Hersberger, Universität Basel, Switzerland

Reviewed by:

Sunita Nair, Other
Alexandros A. Polymeris, Department of Neurology, University Hospital of Basel, Switzerland  

Copyright: © 2018 Hurtado, GARCIA-SEMPERE, Rodríguez-Bernal, Santa-Ana-Tellez, Peiró and Sanfélix-Gimeno. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Gabriel Sanfélix-Gimeno, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, 46015, Spain,