Real-world analysis of adherence, persistence, and outcomes in patients receiving four-drug antihypertensive therapy.

AIMS: Describe real-world use, adherence, persistence, and risk of non-fatal cardiovascular events (CVE) and mortality among patients receiving four-drug antihypertensive therapy. METHODS AND RESULTS: This was a retrospective, longitudinal cohort study of Italian administrative healthcare databases (N=7,160,298). Eligible patients were ≥18 years and received four-drug therapy between 2018 and 2022. Class- and molecule-level subcohort analyses required data for ≥1 year either side of four-drug therapy identification. Adherence and persistence were based on prescription availability. A Cox proportional hazards model was used for risk assessment.Among 228,594 eligible patients, 113,755 received either an angiotensin-converting enzyme inhibitor (ACEi; n=57,473) or angiotensin II receptor blocker (n=56,282), thiazide/thiazide-like diuretic (DIU), calcium channel blocker (CCB), and a fourth class (mostly beta-blockers [BBs]; n=87,022).In the Class subcohort (ACEi+DIU+CCB+BB; n=41,903), high adherence was more frequent among patients receiving two (52.1%) versus three (40.2%) or four (25.0%) pills (global P<0.001); persistence was also improved (P<0.02 from 6 months). Adherence and persistence were significantly higher with two versus three pills in the Molecule subcohort (perindopril, indapamide, amlodipine, and bisoprolol; n=8007). For persistent versus non-persistent patients, there was a risk reduction for CVE (12.4%; P<0.001) and mortality (16.4%; P<0.001) in the Class subcohort, with similar findings in the Molecule subcohort (20.9% [P=0.003] and 20.9% [P=0.002], respectively). CONCLUSION: In patients receiving four-drug antihypertensive therapy, adherence and persistence were significantly improved with lower pill burden. Persistence was associated with lower risks of CVE and mortality.