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Zofenopril or irbesartan plus hydrochlorothiazide in elderly patients with isolated systolic hypertension untreated or uncontrolled by previous treatment

a double-blind, randomized study

Modesti, Pietro A.; Omboni, Stefano; Taddei, Stefano; Ghione, Sergio; Portaluppi, Francesco; Pozzilli, Paolo; Volpe, Massimo; Arca, Marcello; Calabrò, Paolo; Fulgheri, Paolo L. Dessì; Bucci, Marco; Berra, Sergio; Villani, Giovanni Q.; Vladoianu, Mircea; Popescu, Elena; Velican, Valerica G.; Pirvu, Octavian

doi: 10.1097/HJH.0000000000000805
ORIGINAL PAPERS: Therapeutic aspects

Objective: To compare zofenopril + hydrochlorothiazide (Z + H) vs. irbesartan + hydrochlorothiazide (I + H) efficacy on daytime SBP in elderly (>65 years) patients with isolated systolic hypertension (ISH), untreated or uncontrolled by a previous monotherapy.

Methods: After a 1-week run-in, 230 ISH patients (office SBP ≥ 140 mmHg and DBP < 90 mmHg + daytime SBP ≥ 135 mmHg and daytime DBP < 85 mmHg) were randomized double-blind to 18-week treatment with Z + H (30 + 12.5 mg) or I + H (150 + 12.5 mg) once daily, in an international, multicenter study. Z and I doses could be doubled after 6 and 12 weeks, and nitrendipine 20 mg added at 12 weeks in nonnormalized patients.

Results: In the full analysis set (n = 216) baseline-adjusted average (95% confidence interval) daytime SBP reductions after 6 weeks (primary study end point) were similar (P = 0.888) with Z + H [7.7 (10.7, 4.6) mmHg, n = 107] and I + H [7.9 (10.7, 5.0) mmHg, n = 109]. Daytime SBP reductions were sustained during the study, and larger (P = 0.028) with low-dose Z + H at study end [16.2 (20.0, 12.5) mmHg vs. 11.2 (14.4, 7.9) mmHg I + H]. Daytime SBP normalization (<135 mmHg) rate was similar under Z + H and I + H at 6 and 12 weeks, but more common under Z + H at 18 weeks (68.2 vs. 56.0%, P = 0.031). Both drugs equally reduced SBP in the last 6 h of the dosing interval and homogeneously reduced SBP throughout the 24 h. The proportion of patients reporting drug-related adverse events was low (Z + H: 4.4% vs. I + H: 6.0%; P = 0.574).

Conclusion: Elderly patients with ISH respond well to both low and high-dose Z or I combined with H.

aDepartment of Clinical and Experimental Medicine, Careggi Hospital, University of Florence, Florence

bItalian Institute of Telemedicine, Varese

cThe ZEUS Study Group, Italy

dThe ZEUS Study Group, Romania

Correspondence to Professor Pietro A. Modesti, Department of Clinical and Experimental Medicine, Careggi Hospital, University of Florence, Viale Giovan Battista Morgagni 85, 50134 Firenze, Italy. Tel: +39 055 7949376; fax: +39 055 4378638; e-mail:

Abbreviations: ABPM, ambulatory blood pressure monitoring; ACE, angiotensin-converting enzyme; ACR, albumin–creatinine ratio; AI, augmentation index; ARB, angiotensin II receptor blocker; BP, blood pressure; DBP, diastolic blood pressure; ISH, isolated systolic hypertension; PWV, pulse wave velocity; RAS, renin angiotensin system; SI, smoothness index; SBP, systolic blood pressure

Received 24 June, 2015

Revised 3 September, 2015

Accepted 20 October, 2015

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