Medication Adherence to Antihypertensive Triple-Combination Therapy Among Patients Enrolled in a Medicare Advantage...

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.

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.

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.

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.

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.

No outside funding supported this study. Abughosh reports grants from Sanofi, Regeneron, Valeant Pharmaceuticals, BMS/Pfizer, and PhRMA, not related to this study. Serna reports employement with CareAllies, a Cigna company. The other authors have no conflicts of interest to disclose.