Medication Adherence to Antihypertensive Combination Therapy
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Abstract
Introduction: Approximately 32% (75 million) of adults have hypertension in US and more than 1,100 deaths and 48 billion dollars are attributable to hypertension annually. Combination therapy in the treatment of hypertension has been shown to improve both blood pressure control and tolerability. Currently, only three single pill triple-combination therapies are available in the market for the treatment of hypertension, which are Exforge HCT®, Tribenzor® Amturnide®. Medication adherence has become a major concern for the health care system and non-adherence is associated with higher risk of morbidity and mortality.
Objective: To compare medication adherence rate of single pill fixed-dose triple combination therapy vs free drug triple combination therapy vs fixed-dose dual combination therapy along with a third agent in patients with hypertension enrolled in a Medicare advantage plan using two different definitions of adherence measures.
Methods: A retrospective cohort study was conducted using Cigna-Health-Spring’s medical claims database. The study population consisted of elderly patients with hypertension enrolled in the Medicare prescription drug plan in Texas between January 2014 and December 2016. Antihypertensive combination therapy users were classified into three groups (group I: single pill triple combination group; group II: fixed dose dual combination plus a third agent group; group III: free triple combination group). Adherence rate using proportion of days covered (PDC) was calculated for each group within a one year follow up period using two adherence definitions. The first adherence measurement definition was the total number of days with all three drug classes available divided by the total number of days during the follow up period. The second adherence measurement definition was the total number of days with at least one drug class available divided by the total number of days during the follow up period. Descriptive statistics were provided for the patients’ demographic factors and other variables. Group differences were assessed using chi- square tests for binary variables and student’s t-tests for continuous variables. Multivariate logistic regression model was conducted to assess the influential factors for medication adherence after controlling for potential confounders with the outcome variable of adherent vs. not (using 0.8 as a cut off). Major independent variable was type of combination therapy (categorized as single pill triple combination therapy vs. fixed dose dual combination plus a third agent vs. free combination therapy from three drug classes). Other independent variables included: age, gender, language, health plan (LIS status), comorbidities (myocardial infarction, coronary artery disease, peripheral vascular disease, diabetes, COPD, heart failure, renal disease, obesity, stroke, hyperlipidemia, depression, dementia), Centers for Medicare and Medicaid Services (CMS) risk score, previous hospitalization history and previous antihypertensive drug use history during the baseline period (six months prior to the treatment).
Results: A total of 10,836 triple combination users with diagnosis of hypertension and aged more than 65 were identified. In the main analysis using the 1st adherence definition, single pill triple combination user group consisted of 336 (3.10%) patients with a mean PDC of 0.67. The fixed dose dual combination plus a third agent group consisted of 470 (4.34%) patients with a mean PDC of 0.37and the free triple combination group consisted of 10,030 (92.56%) patients with a mean PDC of 0.50. Overall, the adherence rate to single pill triple-dose dual combination therapy was higher than free drug triple combination therapy and fixed dose dual combination therapy along with one pill monotherapy. Of the 10,836 patients, 2,845 (26.25%) were classified as adherent with PDC equal to or more than 0.8 and 7,991(73.74%) were classified as non-adherent with PDC less than 0.8. In the multivariate logistic regression model of using 1st adherence definition, fixed dose dual combination plus a third agent therapy was significantly associated with lower adherence compared to single pill triple combination therapy agent (OR:0.177, 95% CI (0.119-0.263), p<0.001), however, no significant difference was detected between single pill triple combination in comparison to free combination therapy. Younger age, female gender, language (Spanish), some comorbidities and previous hospitalization history significantly were found to have a negative effect on medication adherence. When the 2nd adherence definition was applied, 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), p<0.001).
Conclusion: Medication adherence is a complex issue affected by various influential factors. Measuring adherence to multiple concurrent regimens is complicated and there is a big variation in the adherence rates when different adherence measurement criteria is applied. Other influential factors which significantly associated with medication adherence included age, gender, language, some comorbidities and previous hospitalization history.