Real-world analysis of adherence, persistence, and outcomes in patients receiving four-drug antihypertensive therapy
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
- Outcome
- High adherence (class subcohort)
Methodological detailsItalian administrative healthcare databases, Cox proportional hazards model
- Italian administrative healthcare databases
- Cox proportional hazards model
Main finding
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | Risk reduction | P value |
|---|---|---|
| Risk reduction for CVE and mortality, persistent vs. non-persistentPersistent vs non-persistent · CVE, class subcohort | 12.4% | P < 0.001 |
| Risk reduction for CVE and mortality, persistent vs. non-persistentPersistent vs non-persistent · mortality, class subcohort | 16.4% | P < 0.001 |
| Risk reduction for CVE and mortality, persistent vs. non-persistentPersistent vs non-persistent · CVE, molecule subcohort | 20.9% | P = 0.003 |
| Risk reduction for CVE and mortality, persistent vs. non-persistentPersistent vs non-persistent · mortality, molecule subcohort | 20.9% | 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.
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