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

Abstract

Objective: 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 at least two (D2) refills for inclusion in the cohorts. Finally, we assessed the impact of adherence on health outcomes according to each method.Methods: Population-based retrospective cohort of all patients with Non Valvular Atrial Fibrillation (NVAF), who were newly prescribed acenocoumarol, apixaban, dabigatran or rivaroxaban from November 2011 to December 2015 in the region of Valencia (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) defined according to each method of calculation and health 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.Results: 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 was associated with a reduced 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.Conclusion: Common approaches to assess adherence using measures based on days’ supply exclude groups of non-adherent patients and, also, misattribute periods of doctors’ discontinuation to patient non-adherence, misestimating adherence overall. Physician-initiated discontinuation is a major contributor to reduced OAC exposure. 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 days’ supply measures. High adherence and high exposure to OAC treatment in NVAF patients is associated with better health outcomes.

Adherence to direct oral anticoagulant treatment for atrial fibrillation in the Netherlands: A surveillance study

“…We found 11 observational studies 4 , 5 , 13 , 14 , 30 , 31 , 32 , 33 , 34 , 35 , 36 that investigated adherence of patients to DOAC treatment of which 7 were restricted to atrial fibrillation patients with a follow‐up of more than 6 months. 4 , 5 , 14 , 30 , 31 , 32 , 33 The proportion of atrial fibrillation patients with a PDC of ≥80% in five of these studies ranged from 72% to 77%, 4 , 5 , 14 , 30 , 31 , 32 , 33 which is similar to what we found in our study.…”

“…We found 11 observational studies 4 , 5 , 13 , 14 , 30 , 31 , 32 , 33 , 34 , 35 , 36 that investigated adherence of patients to DOAC treatment of which 7 were restricted to atrial fibrillation patients with a follow‐up of more than 6 months. 4 , 5 , 14 , 30 , 31 , 32 , 33 The proportion of atrial fibrillation patients with a PDC of ≥80% in five of these studies ranged from 72% to 77%, 4 , 5 , 14 , 30 , 31 , 32 , 33 which is similar to what we found in our study. The study by Maura et al, which included a total of 22 267 patients with atrial fibrillation, using either dabigatran (n = 11 141) or rivaroxaban (n = 11 126) found a relatively low proportion of patients using a DOAC with a PDC of ≥80% (61%).…”

Reducing Stroke Risk in Atrial Fibrillation: Adherence to Guidelines Has Improved, but Patient Persistence with Anticoagulant Therapy Remains Suboptimal

“…Good adherence, defined as PDC >0.80, is associated with reduced risk of all-cause mortality (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.81–0.91) and ischaemic stroke (HR, 0.69; CI, 0.56–0.85) as shown from data from the Valencia Health System database in Spain (n=37,774) 50). Conversely, poor adherence (PDC<0.80) at 12-month follow-up is associated with a significantly higher risk of both ischaemic stroke (HR, 2.08; CI, 1.11–3.88) and deep vein thrombosis (HR, 5.39; CI, 1.78–16.3) 51).…”

Stroke Incidence and Death in Atrial Fibrillation Patients Newly Treated with Direct Oral Anticoagulants

“… 3 The better adherence or persistence to DOAC compared to VKA is still being discussed, as studies have yet to find any differences, 4 including in France. 5 Furthermore, several studies have shown that non-adherence to VKA therapy was associated with an increased risk of stroke, 6 similarly to DOAC. 3 , 7 Nevertheless, very few studies have reported the association between non-adherence to DOAC and the incidence of thrombo-embolic events, and almost none after more than 1-year of follow-up.…”