Antihypertensive Efficacy of Olmesartan Medoxomil and Ramipril in Elderly Patients with Mild to Moderate Hypertension Grouped According to Renal Function Status

Abstract

The objective of this study was to compare the antihypertensive efficacy and safety of the angiotensin II antagonist olmesartan medoxomil and the ACE inhibitor ramipril in elderly patients with mild to moderate essential hypertension, grouped according to renal function. We performed a post hoc analysis of pooled data from two randomized, double-blind, parallel-group, multicentre studies. After a 2-week placebo wash-out period, 1453 mild to moderate hypertensive subjects were randomized to a 12-week treatment with olmesartan medoxomil 10 mg/day or ramipril 2.5 mg/day. After 2 and 6 weeks, doses were increased up to a maximum of 40 mg/day (olmesartan medoxomil) and 10 mg/day (ramipril) in non-normalized subjects (office systolic blood pressure [SBP] ≥ 140 mmHg or diastolic blood pressure [DBP] ≥90 mmHg in non-diabetic subjects and office SBP ≥ 130 mmHg or DBP ≥80 mm Hg in diabetic patients). Office blood pressure (BP) was measured at 0, 2, 6 and 12 weeks, 24-hour ambulatory BP at 0 and 12 weeks. 284 patients treated with olmesartan medoxomil 40 mg/day at the end of the double-blind period entered a 36-week, open-label follow-up. Renal function (Cockroft-Gault equation) was evaluated as normal or increased estimated glomerular filtration rate (eGFR) [≥90 mL/min/1.73 m(2)], mild eGFR reduction (60-90 mL/min/1.73 m(2)) and moderate or severe eGFR reduction (<60 mL/min/1.73 m(2)). 181 (12.7%) subjects had normal or increased eGFR, 840 (58.9%) mild eGFR reduction, and 405 (28.4%) moderate or severe eGFR reduction. Baseline-adjusted office BP reductions were superior with olmesartan medoxomil than with ramipril in normal or increased (olmesartan medoxomil - ramipril difference SBP: 5.0 mmHg [95% CI 9.1, 0.9], p = 0.018; DBP: 2.7 mmHg [4.8, 0.6], p = 0.011) and mildly reduced eGFR patients (SBP: 1.6 mmHg [3.5, 0.2], p = 0.080; DBP: 1.2 mmHg [2.3, 0.2], p = 0.022). In the group with moderately or severely reduced eGFR the two treatments were comparable (SBP: 1.9 mmHg [4.6, 0.9], p = 0.185; DBP: 0.8 mmHg [2.3, +0.7]; p = 0.296). At 12 weeks, the rate of normalized patients was 46.1 % with olmesartan medoxomil versus 23.9% with ramipril (p = 0.002) in the normal, and 49.9% versus 42.7% (p = 0.037) in the mild eGFR reduction group. No significant differences in normalization rate were observed in the moderately or severely reduced eGFR group (olmesartan medoxomil 49.5% vs ramipril 46.3%, p = 0.519). eGFR did not show any significant change during treatment. Olmesartan medoxomil provides a more effective BP control, similar if not superior to that of ramipril, independently from the patient's renal function status.