A medication adherence and persistence comparison of hypertensive patients treated with single-, double- and triple-pill combination therapy

Objective: Fixed-dose combination therapy reduces pill burden and may, therefore, improve medication adherence and health outcomes. This study compared adherence to and persistence with single-, double-, and triple-pill treatment regimens among hypertensive patients in a US clinical practice setting. Methods: Adults with hypertension treated with three anti-hypertensive medications were identified. Index date was the first occurrence of a single-, double-, or triple-pill regimen with olmesartan or valsartan plus amlodipine and hydrochlorothiazide from July 2010 to September 2011. Patients were followed for 12 months to assess adherence (proportion of days covered [PDC] >= 80%) and time to discontinuation (medication gap >= 60 days) of the index regimen. Multivariate regression models were used to compare adjusted outcomes. Results: The number of prescribed pills in the index regimen was monotonically related to adherence with 55.3%, 40.4% and 32.6% of patients having PDC >= 80% in the single-, double- and triple-pill cohorts, respectively. In adjusted analysis, patients in the double- (odds ratio [OR]: 0.45; 95% confidence interval [CI]: 0.42-0.48) and triple-pill (OR: 0.26; 95% CI: 0.22-0.30) cohorts were less likely to be adherent to their index regimens than those in the single-pill cohort. Double-pill (hazard ratio [HR]: 1.89; 95% CI: 1.74-2.06) and triple-pill patients (HR: 2.49; 95% CI: 2.14-2.88) were more likely to discontinue treatment than single-pill patients. Conclusions: Greater pill burden was directly and significantly associated with decreased adherence and persistence with antihypertensive therapies in real-practice settings. Use of fixed-dose combinations that reduce pill burden could help patients to continue treatment and may result in improved clinical outcomes. Typical of observational studies, the potential for residual confounding of adherence estimates remains due to lack of randomization of treatment groups.