Adherence and related cardiovascular outcomes to single pill vs. separate pill administration of antihypertensive triple-combination therapy

Objective:To compare adherence to antihypertensive treatment between patients prescribed a three-drug single-pill combination (SPC) of perindopril/amlodipine/indapamide (P/A/I) vs. the combination of an angiotensin-converting enzyme inhibitor (ACEI), a calcium-channel blocker (CCB), and a diuretic (D) as a two-drug SPC plus a third drug given separately.Methods:Using the healthcare utilization database of the Lombardy Region (Italy), the 28 210 patients, aged at least 40 years, who were prescribed P/A/I SPC during 2015-2018 were identified and the date of the first prescription was defined as the index date. For each patient prescribed the SPC, a comparator who started ACEI/CCB/D treatment as a two-pill combination was considered. Adherence to the triple combination was assessed over the year after the index date as the proportion of the follow-up days covered by prescription (PDC). Patients who had a PDC >75% were defined as highly adherent to drug therapy. Log-binomial regression models were fitted to estimate the risk ratio of treatment adherence in relation to the drug treatment strategy.Results:About 59 and 25% of SPC and two-pill combination users showed high adherence, respectively. Compared with patients under a three-drug two-pill combination, those who were treated with the three-drug SPC had a higher propensity to be highly adherent to the triple combination (2.38, 95% confidence interval: 2.32-2.44). This was the case regardless of the sex, age, comorbidities, and number of co-treatments.Conclusions:In a real-life setting, patients under three-drug SPC exhibited more frequently a high adherence to antihypertensive treatment than those prescribed a three-drug two-pill combination.