Hydrochlorothiazide and spironolactone in hypertension

Abstract

A double-blind study of hydrochlorothiazide and spironolactone, alone and in combination, was conducted in 49 patients with mild-to-moderate essential hypertension after a 4-wk placebo washout period. In the whole group mean arterial blood pressure fell to levels of less than or equal to 107 mm Hg or declined by more than 15 mm Hg in 78% of the patients after twelve weeks of treatment. Sixty-nine percent of patients receiving hydrochlorothiazide alone developed serum potassium levels lower than 3.5 mEq/L; serum potassium levels were above 5.5 mEq/L in 2 patients (5.5%) receiving spironolactone 400 mg/day. Uric acid levels rose in all patients, more in those on hydrochlorothiazide, but clinical gout did not develop in any subject. Hydrochlorothiazide, spironolactone, and the combination of the two are effective antihypertensives. Spironolactone in doses of 200 and 400 mg/day was associated with side effects but did not induce a greater antihypertensive effect than doses of 100 mg/day. Our data suggest that when hydrochlorothiazide is associated with potassium loss, when gout or elevated uric acid levels are of concern, or when carbohydrate tolerance is abnormal, supplementation or replacement with spironolactone (up to 100 mg/day) may be useful in controlling blood pressure while reducing side effects.

A Comparison of the Aldosterone‐blocking Agents Eplerenone and Spironolactone

“…In two studies that defined hyperkalemia as serum potassium 5.5 mEq/L, the incidence of hyperkalemia ranged from 3% to 6% at spironolactone doses of 12.5 to 400 mg/day. 23,24 At the 5.5 mEq/L threshold, the incidence of eplerenone-induced hyperkalemia ranged from 1%-3% at doses of 50-200 mg/day. 25 -27 For studies that used a serum potassium threshold 6.0 mEq/L, the incidence of hyperkalemia ranged from 0% to 11% at eplerenone doses of 50-200 mg/day.…”

Valsartan and hydrochlorothiazide in patients with essential hypertension. A multiple dose, double-blind, placebo controlled trial comparing combination therapy with monotherapy

“…8,9 Hydrochlorothiazide (HCTZ) is a thiazide diuretic which is commonly used for the treatment of essential hypertension, at recommended doses of 12.5 mg or 25 mg. 10 In published clinical studies, HCTZ has been shown to act additively in combination with several classes of antihypertensive medication. [11][12][13][14] In addition to its diuretic effect HCTZ is known to activate the renin-angiotensin system.…”

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

“…Asymptomatic hypokalemia may be a greater risk factor for sudden death than has previously been recognized 1 " 3 and invariably occurs when proximal tubule or loop diuretics are used. 4 Diuretic-induced increases in uric acid may precipitate gout in rare patients or predispose them to urolithiasis. In addition, uric acid has been shown to be a risk factor for coronary artery disease.…”