Defining an evidence-based cutpoint for medication adherence in heart failure

Background Despite the importance of medication adherence in heart failure, clinically relevant cutpoints for distinguishing the level of adherence associated with outcomes are unknown. Objective The purpose of this study is to determine the cutpoint above which there is a positive relationship between level of medication adherence and event-free survival. Methods This was a longitudinal study of 135 patients with heart failure. Medication adherence was measured using a valid and objective measure, the Medication Event Monitoring System. Two indicators of adherence were assessed by the Medication Event Monitoring System (AARDEX, Union City, CA): (1) dose count, percentage of prescribed doses taken, and (2) dose days, percentage of days the correct number of doses was taken. Patients were followed up to 3.5 years to collect data on outcomes. A series of Kaplan-Meier plots with log-rank tests, Cox survival analyses, and receiver operating characteristic curves were assessed comparing event-free survival in patients divided at one-point incremental cutpoints. Results Event-free survival was significantly better when the prescribed number of doses taken (dose count) or the correct dose (dose day) was >= 88%. This level was confirmed in a Cox regression model controlling for age, gender, ejection fraction, New York Heart Association, comorbidity, angiotensin-converting enzyme inhibitor use, and p-blocker use. Receiver operating characteristic curves showed that adherence rates above 88% produced the optimal combination of sensitivity and specificity with respect to predicting better event-free survival. With 88% as the adherence cutpoint, the hazard ratio for time to first event for the nonadherent group was 2.2 by dose count (P =.021) and 3.2 by dose day (P =.002). Conclusion The results of this study provide clinicians and researchers with an evidence-based recommendation about the level of adherence needed to achieve optimal clinical outcomes. (Am Heart J 2009; 157:285-91.)