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

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. 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. 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%). 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. Real-world evidence suggests that simplifying treatment for high blood pressure by combining several medicines into a single pill helps patients to manage their therapy, ultimately improving both adherence and persistence. This, in turn, may be linked to a lower risk of cardiovascular events. However, previous studies have been limited by short follow-up, preventing assessment of whether these benefits persist over time. In this study, we examined whether the previously described benefits of single-pill combinations are maintained over a longer period—up to 10 years—and whether they are associated with a meaningful reduction in illness and death related to high blood pressure. We analysed data from more than 24,000 people with hypertension in Italy who were treated with combinations of blood pressure medications containing perindopril (chosen because these were among the first single-pill combinations available on the Italian market). Our analysis showed that compared with taking multiple, separate pills, treatment with a single pill was linked with patients taking their daily medication more consistently over a 10-year period. People receiving single pills also had a lower risk of heart disease and death. Our study shows that receiving single pill treatments for high blood pressure instead of multiple, separate pills could result in better clinical outcomes for real-world patients.