Comparative and Combined Efficacy of Doxazosin and Enalapril in Hypertensive Patients

Twenty patients with essential hypertension were randomised to a 7-week period of dose titration with doxazosin, 1-8mg/day or enalapril, 5-20mg/day. In a further 7-week period the dosage level reached with the initial drug was halved, and titration with the second agent was carried out. Blood pressure responses at the end of each treatment period were assessed by clinic measurements made 24 hours post-dose. In the first treatment period, enalapril (mean dose 19mg/day) reduced serum free ACE activity by 40% and had a greater effect than doxazosin (mean dose 5.2mg/day) on clinic supine blood pressure (systolic and diastolic). In the second period, the addition of enalapril to doxazosin was associated with a significant fall in clinic standing blood pressure (systolic and diastolic), despite the doxazosin dose reduction and consequent decrease in median plasma doxazosin concentration (from 10.6 to 5.2ng/ml). Alternatively, when doxazosin was added to enalapril, free ACE activity remained 40% decreased despite enalapril dose reduction, and blood pressure was not further affected. Plasma renin activity was increased by enalapril. No changes were observed in plasma aldosterone or lipid concentrations with either drug. The combination of doxazosin and enalapril was well tolerated and lowered blood pressure overall. Judged by clinic measurements 24 hours post-dose, most of the antihypertensive effect was attributable to the enalapril component. However, ambulatory blood pressure monitoring 0-12 hours post-dose in a subset of patients suggested a contribution of doxazosin earlier in the dose interval.