Adherence and Healthcare Costs Associated with Single-vs Free-Pill Combination of Perindopril-Based Antihypertensive Medications: An 11-Year Follow-Up, Real-World Evidence

BACKGROUND: Short-term studies have demonstrated that single-pill combinations (SPCs) improve adherence, reduce hypertension-related complications, and lower costs; however, long-term benefits remain unclear. This study compared adherence, healthcare resource utilization (HCRU), and costs over 11 years in patients treated with SPCs versus free-pill combinations (FPCs) of antihypertensive drugs in routine Italian practice. METHODS: We analyzed a large administrative dataset (2010-2022) covering approximately 7 million Italian citizens. Adults initiating perindopril (PER)-based SPC or FPC with amlodipine and/or indapamide were included. PER-based therapies were selected because their SPCs were among the first marketed in Italy, allowing for extended follow-up. Adherence was measured by proportion of days covered (PDC), with high adherence defined as PDC ≥ 80%. RESULTS: Among 24,476 patients (mean age: 64.6 years; 59.7% male), 92.6% received SPCs, and 6.0% FPCs. High adherence was observed in 75.5% of SPC users compared with 32.0% of FPC users. SPC users had fewer all-cause hospitalizations and outpatient visits (both p < 0.001). Average annual healthcare costs were €242.96 lower for SPC users (95% CI €55.03-€430.89; p < 0.05), with significant reductions in costs related to all-cause and cardiovascular-related hospital admissions (p < 0.001). CONCLUSIONS: In this long-term, real-world study, SPC use was associated with better adherence, reduced HCRU, and lower healthcare costs compared with FPC regimens. These economic benefits were evident within 1 year and may yield substantial long-term savings for national health systems, given the high prevalence and chronic nature of hypertension.