COMPARATIVE AND COMBINED EFFICACY OF DOXAZOSIN AND ENALAPRIL IN HYPERTENSIVE PATIENTS

Twenty patients with essential hypertension were randomised to a 7-wee k period of dose titration with doxazosin, 1-8mg/day or enalapril, 5-2 0mg/day. In a further 7-week period the dosage level reached with the initial drug was halved, and titration with the second agent was carri ed out. Blood pressure responses at the end of each treatment period w ere assessed by clinic measurements made 24 hours post-dose. In the fi rst treatment period, enalapril (mean dose 19mg/day) reduced serum fre e ACE activity by 40% and had a greater effect than doxazosin (mean do se 5.2mg/day) on clinic supine blood pressure (systolic and diastolic) . In the second period, the addition of enalapril to doxazosin was ass ociated with a significant fall in clinic standing blood pressure (sys tolic and diastolic), despite the doxazosin dose reduction and consequ ent decrease in median plasma doxazosin concentration (from 10.6 to 5. 2ng/ml). Alternatively, when doxazosin was added to enalapril, free AC E activity remained 40% decreased despite enalapril dose reduction, an d blood pressure was not further affected. Plasma renin activity was i ncreased 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 postdose, most of the antihyper tensive effect was attributable to the enalapril component. However, a mbulatory blood pressure monitoring 0-12 hours postdose in a subset of patients suggested a contribution of doxazosin earlier in the dose in terval.