Impact of Single-Pill Combinations and Level of Adherence on Healthcare Costs in Italian Hypertensive Patients Treated With Perindopril-Based Regimens

OBJECTIVES: Hypertension guidelines recommend initiation and up-titration of anti-hypertensives with single-pill combinations (SPC) to reduce pill burden and improve adherence. Using Italian real-world data, we aim to evaluate and compare healthcare resources utilization and costs (HRUC) among patients on perindopril-based anti-hypertensive therapy (PER-b) classified by formulation type (SPC vs. free-equivalent, FEC) and by adherence level.

METHODS: A retrospective analysis was performed using administrative databases, covering 6.7 million Italians health-assisted during 2010-2021, including hypertensive adults with dual or triple PER-b prescriptions. Adherence, measured by the proportion of days covered (PDC), was categorized as low (<40%), moderate (40%-<80%), or high (≥80%). Mean HRUC per subject per year were calculated. A Generalized Linear Model (GLM) evaluated cost correlations, adjusted for confounders like age, gender, prior treatments, comorbidities, and pill burden.

RESULTS: 1,458 patients on FEC and 22,663 on SPC were included. High adherence was more common in SPC group (75.5%) compared to FEC group (32.0%) (p<0.001). During follow-up, SPC users had fewer numbers of all-cause hospitalizations (all-hosp) (mean±SD 0.2±0.5 vs. 0.4±0.7; p<0.001), cardiovascular hospitalizations (mean±SD 0.04±0.10 vs. 0.09±0.20; p<0.001), drug prescriptions dispensed (mean±SD 15.7±9.4 vs. 19.7±11.1; p<0.001), and reduced use of outpatient services (specialist visits/laboratory tests, mean±SD 4.1±4.7 vs. 4.6±5.2; p<0.001) than FEC users. Mean annual healthcare costs (considering drug prescriptions dispensed, all-hosp and outpatient services) were significantly lower for the SPC vs. FEC group (€2,077±3,212 vs. €2,892±4,271; p<0.001). Higher adherence was associated with lower healthcare costs (€2,056±2,923 for PDC≥80% vs. €2,576±4,555 for PDC<40%; p<0.05). GLM analysis confirmed higher costs for FEC and lower costs for adherent patients, with FEC increasing costs by €243 per patient/year compared to SPC.

CONCLUSIONS: SPC regimen appears to be associated with lower healthcare expenditure than FEC regimens. High adherence significantly reduces HRUC, emphasizing the importance of strategies to improve patient compliance with anti-hypertensive therapy.