Pilot study of combined blockade of the renin-angiotensin system in essential hypertensive patients

Background Additive hemodynamic effects of combined blockade of the renin-a ngiotensin system by an angiotensin I converting enzyme inhibitor and an an giotensin II antagonist have been observed in sodium-depleted normotensive volunteers and in patients with congestive heart failure. Objective To investigate whether the same additive hemodynamic effects occu r in patients with hypertension and to verify the safety of such an approac h. Design Multicenter, randomized, double-blind, parallel-group, pilot study. Patients 177 patients with mild-to-moderate hypertension [diastolic blood p ressure (DBP): 95-115 mmHg after a 4-week placebo run-in period] were inclu ded in the study. Intervention Combination therapy consisting of 50 mg losartan daily and 10 mg enalapril daily was administered for 6 weeks. The effects of this therap eutic regimen was compared with similar groups of patients who received eit her 50 mg losartan daily or 10 mg enalapril daily Main outcome measures 24-hour ambulatory mean DBP and clinic DBP measured a t trough after 6 weeks of treatment. Results 24-hour ambulatory mean DBP did not significantly differ between tr eatment groups although the combination tended to lower BP more. The combin ation therapy was more effective on clinic DBP measured at trough than was losartan by 3.2 mmHg [confidence interval (95%, CI) 0.7-5.7 mmHg, P = 0.012 ], and more effective than enalapril by 4.0 mmHg (95% CI, 1.5-6.4 mmHg, P = 0.002). In a subgroup of 28 patients, higher plasma active renin and angio tensin I levels during blockade by the combination therapy were observed. T his finding confirmed that the combination of the two agents inhibited the renin-angiotensin system to a greater extent than did either agent alone. Conclusion A combination of 10 mg enalapril daily and 50 mg losartan daily safely induces a supplementary, although modest, fall in clinic DBP in pati ents with mild-to-moderate essential hypertension. J Hypertens 2000, 18:113 9-1147 (C) Lippincott Williams & Wilkins.