Medication adherence to antihypertensive triple-combination therapy among patients enrolled in a Medicare advantage plan

Abstract

BACKGROUND: Approximately 32% (75 million) of adults have hypertension in the United States, leading to 1,100 daily deaths and costing more than $48 billion annually in medical expenditures. Approximately 25% of patients with hypertension require triple combination therapy to reach recommended blood pressure. Currently, only 3 single-pill triple-combination therapies are available in the market for the treatment of hypertension. Medication adherence has become a major concern for the health care system, and nonadherence is associated with higher risks of morbidity and mortality. OBJECTIVE: To compare medication adherence rates among single-pill triple-combination therapy, free triple-combination therapy, and fixed-dose dual-combination therapy plus a third agent in hypertensive patients enrolled in a Medicare Advantage prescription drug plan using 2 adherence definitions. METHODS: A retrospective cohort study was conducted using Cigna-HealthSpring's medical claims database from January 2014 to December 2016. Antihypertensive combination therapy users were classified into a single-pill triple-combination group, a fixed-dose dual-combination plus a third agent group, and a free triple-combination group. Adherence rates using proportion of days covered (PDC) were calculated for each group within a 1-year follow-up period using 2 definitions: a strict one requiring all antihypertensive agents during follow-up and a more relaxed definition requiring any antihypertensive agent during follow-up. Descriptive statistics were examined, and group differences were assessed using chi-square and analysis of variance. Multivariate logistic regression was conducted to control confounders of adherence using both definitions. RESULTS: 10,836 triple-combination users were identified. In the multivariate model using the first definition, fixed-dose dual-combination plus a third agent was significantly associated with lower adherence compared with single-pill triple therapy (OR=0.177; 95% CI=0.119-0.263; P<0.001). No significant difference was detected between single-pill triple-combination therapy in comparison with free-combination therapy. In the multivariate model using the second definition, fixed-dose dual-combination plus a third agent and free-combination therapy were significantly associated with better adherence in comparison with single-pill triple combination therapy (OR=3.62, 95% CI=2.59-5.05; OR=4.31, 95% CI=2.15-8.64, respectively). Younger age, female gender, language (Spanish), some comorbidities, and previous hospitalization had a negative effect on adherence. CONCLUSIONS: Measuring adherence to multiple concurrent regimens is complicated and different adherence definitions can result in significant variations in adherence measures. Future research evaluating clinical outcomes with various definitions is needed.