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

Abstract

SUMMARY 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. 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. Diuretics were among the first antihypertensive agents, followed by a number of increasingly specialized and effective agents. Since the advent of antihypertensive therapy, several studies have been conducted demonstrating the beneficial effect of blood pressure reduction on cardiovascular morbidity and mortality. Recent studies have been interpreted by some investigators as suggesting that certain antihypertensive drugs, particularly those of the diuretic

Once vs twice daily administration of a fixed combination of captopril plus hydrochlorothiazide in essential hypertension: a double‐blind crossover study in known responders to a standard combination.

“…The results of this multicentre trial of mild to moderate essential hypertension show that the fixed combination of C 50/HCTZ 25 once daily provided an antihypertensive effect equal in magnitude to that of the fixed combination of C 25/HCTZ 12.5 twice daily in patients already controlled by the co-administration of C 25 mg and HCTZ 12.5 mg twice daily. Moreover this study confirms previous reports (Weinberger, 1982(Weinberger, , 1983(Weinberger, , 1985 demonstrating the additive effect of the two agents on blood pressure. Indeed, beneficial blood pressure response (normalized blood pressure or decreased by 10% or more) was seen in 88% of the patients as reported by Clementy et al (1988).…”

Effectiveness and metabolic effects of perindopril and diuretics combination in primary hypertension

“…8,22,23 Accordingly, previous studies have shown that the addition of ACE inhibitors to thiazides can blunt or even prevent the metabolic consequences of diuretic therapy, while they enhance their antihypertensive effect. [6][7][8][9][10][11] Nonetheless, there seem to be a few studies concerning the metabolic consequences of added thiazide diuretics to ACE inhibitors. Additionally, comparison of the observed biochemical derangements between hydrochlorothiazide and indapamide when added to ACE inhibitors is lacking.…”

“…26 Furthermore, the ACE inhibitor dosage could have also played a role in its influence in the carbohydrate tolerance, since in one study the administration of only high doses of captopril (Ͼ100 mg/day) mitigated the hyperglycaemic effect of hydrochlorothiazide. 6 Therefore, a placebo-controlled study to address the effect of ACE inhibition on sensitivity to insulin in essential hypertension needs to be carried out.…”

“…[2][3][4][5] Even though diuretics exert adverse metabolic effects, ACE inhibitors appear to exhibit a neutral or even a beneficial effect on lipid and carbohydrate metabolism, leading to an attenuation of the biochemical sequalae commonly associated with diuretic therapy. [6][7][8][9][10][11] However, indapamide has been reported to induce a moderate change in the serum metabolic parameters. 12,13 Therefore, we undertook the present study to examine the efficacy as well as the metabolic effects evoked a small but statistically significant increase in serum glucose levels while fasting as well as during the 75 g oral glucose challenge.…”

Preventing Thiazide‐Induced Hyperglycemia: Opportunities for Clinical Pharmacists

“…As an alternative, hypokalemia can be minimized if ACE inhibitors or angiotensin II receptor blockers are added to the regimen. 27 …”