Zofenopril or irbesartan plus hydrochlorothiazide in elderly patients with isolated systolic hypertension untreated or uncontrolled by previous treatment: a double-blind, randomized study

Objective: To compare zofenoprilRhydrochlorothiazide (ZRH) vs. irbesartanRhydrochlorothiazide (IRH) 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 SBP140mmHg and DBP<90mmHgRdaytime SBP135mmHg and daytime DBP<85 mmHg) were randomized double-blind to 18-week treatment with ZRH (30R12.5 mg) or IRH (150R12.5 mg) once daily, in an international, multicenter study. Z and I doses could be doubled after 6 and 12 weeks, and nitrendipine 20mg added at 12 weeks in nonnormalized patients. Results: In the full analysis set (n¼216) baseline-adjusted average (95% confidence interval) daytime SBP reductions after 6 weeks (primary study end point) were similar (P¼0.888) with ZRH [7.7 (10.7, 4.6) mmHg, n¼107] and IRH [7.9 (10.7, 5.0) mmHg, n¼109]. Daytime SBP reductions were sustained during the study, and larger (P¼0.028) with low-dose ZRH at study end [16.2 (20.0, 12.5)mmHg vs. 11.2 (14.4, 7.9)mmHg IRH]. Daytime SBP normalization (<135 mmHg) rate was similar under ZRH and IRH at 6 and 12 weeks, but more common under ZRH at 18 weeks (68.2 vs. 56.0%, P¼0.031). 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 (ZRH: 4.4% vs. IRH: 6.0%; P¼0.574). Conclusion: Elderly patients with ISH respond well to both low and high-dose Z or I combined with H.