A Retrospective, Observational Study of Adherence, Persistence and Clinical Outcomes with Perindopril-Based Single-Pill or Free-Pill Antihypertensive Treatments in Italy.

INTRODUCTION: Poor adherence limits the effectiveness of pharmacological treatments. Single-pill combinations (SPCs) improve adherence in short-term observational studies, but whether advantages are sustained long term and translate into clinical benefits remains uncertain. We evaluated long-term improvements in adherence, persistence, and clinical outcomes associated with SPCs. METHODS: Using patient record linking across Italian administrative healthcare databases, we performed a non-interventional, retrospective, observational, longitudinal analysis of hypertension treated with perindopril (PER)-based combinations. We compared adherence [proportion of days covered (PDC)], treatment discontinuation, all-cause mortality, and cardiovascular (CV) event rates between SPCs and free-pill combinations (FPCs) over 10 years. Being the first introduced in Italy, PER-based SPCs were chosen to allow the longest follow-up. RESULTS: Between 2010 and 2022, 24,121 patients with hypertension were treated with PER-based SPCs (n = 22,663) or FPCs (n = 1458). Throughout the 10-year period, ≥ 73% of SPC users had high adherence (PDC ≥ 80%), compared with ≤ 44% of FPC users. Over a 3-year follow-up, discontinuation rates were lower with SPCs (20%) than FPCs (50%). SPCs were associated with lower risks of all-cause mortality (- 27%), CV events (- 31%), ischaemic heart disease (IHD) (- 22%), cerebrovascular events (- 46%), and a composite of mortality/CV events (- 29%) compared with FPCs. Compared with patients with low adherence, those with high adherence had lower risks of all-cause mortality (- 22%), CV events (- 21%), IHD (- 17%), cerebrovascular events (- 33%), and the composite of mortality/CV events (- 22%). CONCLUSION: SPCs are associated with sustained, better adherence and persistence to antihypertensive pharmacological treatments compared with FPCs, which may contribute to real-world clinical benefits. Graphical abstract available for this article.