Do Triple Single-Pill Combinations Make a Difference in Treatment Adherence, Outcomes and Healthcare Resource Utilization in Hypertension? A Real-World Analysis of Patients on Perindopril/Amlodipine/Indapamide in Italy

OBJECTIVES: A real-world analysis was performed to compare adherence, outcomes and healthcare costs in hypertensive patients prescribed perindopril/amlodipine/indapamide (PER/AML/IND) as single-pill vs free combination, in Italy.

METHODS: This retrospective analysis used administrative databases of a sample of Local Health Units covering around 7 million health-assisted individuals. Adult patients treated with PER/AML/IND during 2010-2020 were categorized into 2 cohorts: those taking single-pill or free combination. The index-date (ID) was the first prescription. All patients included had at least 12-months of data available before and after ID. Propensity-score matching (PSM) was applied to minimize selection bias and balance cohorts. Adherence was defined as proportion of days covered (PDC) ≥80%. The incidence of mortality and cardiovascular (CV) events after one-year follow-up was reported as rate per 1,000-person/year. Total healthcare direct costs (sum of costs for all-drugs, hospitalizations, outpatient services) covered by the Italian National Health System (INHS) were reported in Euros (€).

RESULTS: 37,365 patients (mean age 66.0 years, 54.3 % male) were enrolled in the single-pill-cohort and 6,105 (mean age 68.2 years, 50.8% male) in the free-combination-cohort. After PSM, baseline characteristics were balanced among cohorts (6,105 patients in free-combination and 12,150 in single-pill-cohort). In the single-pill-cohort, a significantly higher percentage were adherent versus the free-combination-cohort (59.9% vs 26.9%, p<0.001). The incidence of death and CV events (composite endpoint) was significantly lower in single-pill-cohort compared to free-combination-cohort (105.8 vs 139.0 per 1,000-person/year, p<0.001). In free-combination versus single-pill cohort, total healthcare direct costs were higher (€3,642 vs €2,970, p<0.05). Among major cost drivers, drug-related costs did not decrease significantly (€1,808 vs €1,525, p=0.118), while hospitalizations decreased significantly (€1,262 vs €953, p<0.05).

CONCLUSIONS: This real-world analysis carried out in Italian clinical practice setting demonstrates that PER/AML/IND as single-pill, compared with a free combination, could improve adherence and clinical outcomes and provided cost savings to the INHS (funder).