Influence of an angiotensin converting-enzyme inhibitor on diuretic-induced metabolic effects in hypertension

Abstract

Diuretic therapy is frequently accompanied by undesirable biochemical changes and side-effects. Two multicenter trials compared the effects of captopril combined with a diuretic to the administration of either agent alone in mild-to-moderate hypertensives. In addition to blood pressure, effects on serum potassium, uric acid, glucose, and cholesterol were examined. The first study (Study A) was conducted on 210 such patients randomly assigned to receive: 1) hydrochlorothiazide (H) 15 mg three times daily (t.i.d.); 2) captopril (C) 25 mg t.i.d.; or 3) C + H for 6 weeks. The second study (Study B) involved 415 patients randomly assigned to receive: 1) C 25 mg twice daily (b.i.d.) + H 25 mg b.i.d.; 2) C 50 mg b.i.d. + H 25 mg b.i.d.; 3) C 50 mg b.i.d. + placebo b.i.d.; 4) placebo b.i.d. + H 25 mg b.i.d.; or 5) placebo b.i.d. + placebo b.i.d. for 6 weeks. In both Studies A and B, all patients except those receiving placebo only (Study B-5) had significant (p < 0.05) blood pressure reductions. In Study A, the combination of C + H (A-3) produced a significantly greater (p < 0.001) reduction in blood pressure than either agent alone. In Study B, both C + H groups (B-l, B-2) had a significantly greater (p < 0.01) blood pressure reduction than that seen with C alone (B-3). In Study A, those treated with H alone (A-l) had a significant (p < 0.05) reduction in serum potassium and increases in uric acid, glucose, and cholesterol when compared to C alone (A-2) where no changes in these parameters were observed. Further, the addition of C to H (A-3) blunted the magnitude of changes in potassium and uric acid and prevented the significant rise in glucose and cholesterol seen with H alone. Similar changes were seen in the Study B where H alone was associated with marked (p < 0.05) changes in potassium, uric acid, and glucose. With C alone, no such changes were observed, and with the combination (B-l, B-2) the magnitude of change was again blunted. Taken together, these studies demonstrate the impressive additive antihypertensive effect of combining an angiotensin converting-enzyme inhibitor with a thiazide diuretic. The observations confirm the multiple metabolic effects of thiazide therapy. Finally, these studies indicate that the addition of captopril to hydrochlorothiazide can blunt or even prevent the metabolic consequences of diuretic therapy while enhancing their antihypertensive effect. Thus, this combination has great promise for the treatment of mild-to-moderate hypertension. © 1983 American Heart Association, Inc.