HypertensionCohort study

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

Eur Heart J Cardiovasc PharmacotherPublished

  • retrospective, longitudinal cohort study
  • Italian administrative healthcare databases
  • Cox proportional hazards model

Authors' 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.

Study context

Population
Patients ≥18 years receiving four-drug antihypertensive therapy between 2018 and 2022eligible patients, databases n = 7,160,298 · class subcohort (angiotensin-converting enzyme inhibitor (ACEi) + diuretic (DIU) + calcium channel blocker (CCB) + BB) 41,903 · molecule subcohort (perindopril, indapamide, amlodipine, and bisoprolol) 8,007
Participants
228,594 patients
Exposure
two vs. three or four pills; persistent vs. non-persistent patients

Main finding

As reported in the abstract

High adherence (class subcohort)

Observational data: associations, not effects.

Further findings

Outcomerisk reductionP value
Risk reduction for CVE and mortality, persistent vs. non-persistent — persistent vs non-persistent · CVE, class subcohort12.4%P < 0.001
Risk reduction for CVE and mortality, persistent vs. non-persistent — persistent vs non-persistent · mortality, class subcohort16.4%P < 0.001
Risk reduction for CVE and mortality, persistent vs. non-persistent — persistent vs non-persistent · CVE, molecule subcohort20.9%P = 0.003
Risk reduction for CVE and mortality, persistent vs. non-persistent — persistent vs non-persistent · mortality, molecule subcohort20.9%P = 0.002

Persistence (class subcohort) · from 6 months

persistence was also improved
P < 0.02

Adherence and persistence (molecule subcohort)

significantly higher with two vs. three pills

Regimen composition

received ACEi or angiotensin II receptor blocker, DIU, CCB, and a fourth class
113 755
ACEi
n = 57 473
angiotensin II receptor blocker
n = 56 282
fourth class (mostly beta-blockers [BBs])
n = 87 022

Original publication

Real-world analysis of adherence, persistence, and outcomes in patients receiving four-drug antihypertensive therapy. Eur Heart J Cardiovasc Pharmacother. Published 15 September 2026. doi:10.1093/ehjcvp/pvag073

Summarised from the published abstract; every number is checked against it