Treatment of hypertension with enalapril and hydrochlorothiazide or enalapril and atenolol: contrasts in hypotensive interactions.

To determine the nature of the resultant effect on blood pressure when angiotensin converting enzyme (ACE) inhibitors are combined with other hypotensive agents in the treatment of uncomplicated essential hypertension, two randomized, double-blind, crossover trials were conducted. In each trial there were four treatment phases, each 4 weeks in duration, comprising a 2 X 2 factorial experiment. Twenty-one patients completed the first study in which the effects of enalapril (10 mg twice daily) were compared with hydrochlorothiazide (25 mg twice daily), with the two drugs in combination and with placebo. All blood pressure parameters were reduced in the three active treatment phases compared with placebo (P less than 0.001). Enalapril and hydrochlorothiazide were equally effective and in combination their hypotensive effects were fully additive. Sixteen patients completed the second study which compared the effects of enalapril (20 mg daily), atenolol (50 mg daily), the two drugs in combination and placebo. All blood pressure parameters were again reduced in all phases compared with placebo (P less than 0.001). Enalapril and atenolol were also equally effective, but in combination their hypotensive effects were less than fully additive, with attenuation of the potential additive response by 30-50%. These results indicate that a diuretic-ACE inhibitor combination can be expected to have a greater hypotensive effect than a beta-blocker-ACE inhibitor combination. Both hydrochlorothiazide and atenolol increased plasma atrial natriuretic peptide (ANP) concentrations (P less than 0.01), suggesting that ANP could contribute to the hypotensive effects of these two drug classes.