The impact of adherence to inhaled drugs on 5‐year survival in COPD patients: a time dependent approach

Abstract

PurposeWhether inhaled medications improve long‐term survival in Chronic Obstructive Pulmonary Disease (COPD) is an open question. The purpose of this study is to assess the impact of adherence to inhaled drug use on 5‐year survival in COPD.MethodsA population‐based cohort study in three Italian regions was conducted using healthcare linked datasets (hospitalization, mortality, drugs). Individuals (45+ years) discharged after COPD exacerbation in 2006–2009 were enrolled. Inhaled drug daily use during 5‐year follow‐up was determined through Proportion of Days Covered on the basis of Defined Daily Doses. Five levels of time‐dependent exposure were identified: (i) long‐acting β2 agonists and inhaled corticosteroids (LB/ICS) regular use; (ii) LB/ICS occasional use; (iii) LB regular use; (iv) LB occasional use; and (v) respiratory drugs other than LB. Cox regression models adjusted for baseline (socio‐demographic, comorbidities, drug use) and time‐dependent characteristics (COPD exacerbations, cardiovascular hospitalizations, cardiovascular therapy) were performed.ResultsA total of 12 124 individuals were studied, 46% women, mean age 73,8 years. Average follow‐up time 2,4 year. A total of 3415 subjects died (mortality rate = 11.9 per 100 person years). In comparison to LB/ICS regular use, higher risks of death for all remaining treatments were found, the highest risk for respiratory drugs other than LB category (HR = 1.63, 95%CI 1.43–1.87). Patients with regular LB use had higher survival than those with LB/ICS occasional use (HR = 0.89, 95%CI 0.79–0.99).ConclusionsThese findings support clinical guidelines and recommendations for the regular use of inhaled drugs to improve health status and prognosis among moderate–severe COPD patients. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

Does co-payment for inhaler devices affect therapy adherence and disease outcomes? A historical, matched cohort study

“…Adherence is defined as the process by which patients take their medications as prescribed, comprising 1) initiation of treatment, 2) implementation of the dosing regimen, and 3) persistence with treatment 3. Previous literature has demonstrated that poor adherence can exist among patients with asthma or COPD4–6 and has an impact on disease outcomes 7–9. Contributing factors to poor adherence at the patient level include perceived need of treatment,10 fear of side effects,11 and ability to use inhaler devices correctly 12,13.…”

Investigating the Potential for Bias When Using a Widely Accepted Medication Adherence Measure to Predict Mortality

“…12,14 Four studies assessed adherence in a single measurement over the entire exposure period, 10,14,15,17,20 whereas the remainder used a time-varying approach by breaking the exposure period into intervals that ranged between one-quarter and 3 years. [11][12][13]16,18,19,21 Despite this wide range of work in which PDC or a similar measure was used to estimate the association between adherence and mortality, we were not able to find any studies that assessed whether these measures could produce biased results in some situations. We hypothesized that the outcome event (mortality) could bias the adherence measurement if patient deaths occur during the exposure measurement period.…”

“…PDC and similar measures have been widely used in studies to assess the association between adherence and mortality . These studies used a variety of designs; eight of them established a separate adherence exposure period and excluded patients who died prior to its end date .…”

“…The remainder assessed adherence until death, loss to follow‐up, or the end of the study period, although in two of these studies, the adherence exposure period ended on the date of the patient's last medication fill, as the authors considered medication consumption was less certain for this final fill . Four studies assessed adherence in a single measurement over the entire exposure period, whereas the remainder used a time‐varying approach by breaking the exposure period into intervals that ranged between one‐quarter and 3 years . Despite this wide range of work in which PDC or a similar measure was used to estimate the association between adherence and mortality, we were not able to find any studies that assessed whether these measures could produce biased results in some situations.…”

“…date. 1,10,[15][16][17][18][19]21 The remainder assessed adherence until death, loss to follow-up, or the end of the study period, [11][12][13][14]20 although in two of these studies, the adherence exposure period ended on the date of the patient's last medication fill, as the authors considered medication consumption was less certain for this final fill. 12,14 Four studies assessed adherence in a single measurement over the entire exposure period, 10,14,15,17,20 whereas the remainder used a time-varying approach by breaking the exposure period into intervals that ranged between one-quarter and 3 years.…”