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 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≥140mmHg and DBP<90mmHg+daytime SBP≥135mmHg and daytime DBP<85mmHg) were randomized double-blind to 18-week treatment with Z+H (30+12.5mg) or I+H (150+12.5mg) 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 (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 (<135mmHg) 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 6h of the dosing interval and homogeneously reduced SBP throughout the 24h. 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.