EFFECTS OF QUINAPRIL ADD-ON TREATMENT ON ALDOSTERONE BREAKTHROUGH IN PATIENTS WITH ESSENTIAL HYPERTENSION RECEIVING VALSARTAN: PP.24.466

Abstract

Objective: Angiotensin II receptor antagonists (ARB) are the first choice for treatment on hypertension in patients with essential hypertension (EH). ARB decrease plasma aldosterone concentration (PAC). However, long-term ARB therapy is associated with increased PAC, which is known as ‘ealdosterone breakthrough’. Coadministration of ARB and angiotensin converting enzyme inhibitors (ACEI) is more effective for the treatment of hypertension than monotherapy of either. Nevertheless, little is known about the effect of coadministration of both agents on aldosterone breakthrough. Design and Method: The study was designed to compare the effects of adding quinapril (ACEI) to valsartan (ARB) and doubling the dose of valsartan in patients whose blood pressure did not reach the therapeutic goal (140/90 mmHg) by valsartan (80 mg/day) monotherapy. Sixty-six patients with EH (61±8 years old, 35 men and 31 women, serum creatinine levels <2 mg/dL) already on valsartan 80 mg/day were assigned to receive either a double dose of valsartan (160 mg) or quinapril (10 mg) added to valsartan (80 mg) for 48 weeks. Plasma renin activity (PRA) and PAC were measured at 0, 12, 24 and 48 weeks. Results: Both groups showed significant decreases in blood pressure during the treatment period. In the quinapril add-on group, PAC decreased from 94±6 at 0 week to 71±6 pg/mL at 12 weeks (P < 0.05) and maintained similar levels during therapy. However, in the valsartan double-dose group, PAC initially decreased from 92±8 (0 week) to 74±6 pg/mL (P < 0.05) at 12 weeks but returned to the baseline level (98±9 pg/mL) at 24 weeks. PRA increased from 2.1±0.4 (0 week) to 4.1±1.0 ng/mL/h (p < 0.05, 24 week) in the quinapril add-on group and from 2.6±0.6 (0 week) to 4.5±1.1 ng/mL/h (p < 0.05, 48 week) in the valsartan double-dose group. Conclusion: These findings suggest that adding quinapril to valsartan suppresses aldosterone breakthrough more effectively than increasing the dose of valsartan. Aldosterone increases cardiac fibrosis and promotes ventricular remodeling. Thus, coadministration of ACEI and ARB may minimize these aldosterone-induced deleterious effects.