Diuretics combat the sodium retention of heart failure by inhibiting sodium or chloride resorption at specific sites in the renal tubule. Of the commonly used agents, the loop diuretics, furosemide, torsemide, and bumetanide act in the loop of Henle, whereas thiazides, metolazone, and potassium-sparing agents act in the distal tubule.
All diuretics increase urine volume and sodium excretion, but they differ in their pharmacological properties. Loop diuretics increase sodium excretion to 20% to 25% of the filtered sodium load, enhance free water clearance, and maintain their efficacy unless renal function is severely impaired (creatinine clearance <5 mL/min). In contrast, thiazide diuretics increase fractional sodium excretion to only 5% to 10% of the filtered load, tend to decrease free water clearance, and lose their effectiveness in moderate renal impairment (creatinine clearance <30 mL/min). Loop diuretics are thus preferable in heart failure.
Many short-term controlled studies have shown that diuretics increase urinary sodium excretion and decrease the physical signs of fluid retention in heart failure (jugular venous pressure, pulmonary congestion, ascites, peripheral edema, body weight, etc), within days of starting therapy. Diuretics also relieve symptoms in heart failure, and enhance cardiac function and exercise tolerance. But there have been no long-term studies of diuretic therapy in heart failure, mainly because of ethical difficulties in enrolling symptomatic patients who would benefit from these agents. Thus, their effects on morbidity and mortality are unknown.
Several studies have evaluated the efficacy of diuretic monotherapy in heart failure. In a small study of furosemide alone vs captopril alone, fluid retention was frequent on captopril but not on the diuretic, suggesting that angiotensin-converting enzyme (ACE) inhibitors do not adequately counteract the sodium-avid state that characterizes heart failure. Nevertheless, a large multicenter study in heart failure patients with well-controlled symptoms and fluid retention found that diuretics alone failed to maintain long-term clinical stability. The risk of clinical decompensation was decreased by combining the diuretics with digoxin or an ACE inhibitor. These observations indicate that in fluid retention, diuretics are a necessary component of any successful therapeutic strategy, but are insufficient on their own.
Diuretics play a major role in the treatment of heart failure for three reasons:
Their symptomatic benefit is more rapid than that of any other heart failure drug. They relieve pulmonary and peripheral edema within hours or days, whereas digitalis, ACE inhibitors, and |3-blockers can take weeks or months.
Diuretics are the only drugs that adequately control the fluid retention of heart failure. Although digitalis and low-dose ACE inhibitors enhance urinary sodium excretion, few heart failure patients can maintain sodium balance without using diuretics. However, the successful long-term use of ACE inhibitors and (3-blockers may decrease the need for diuretics in selected patients.
Appropriate use of diuretics is a key element in the success of other heart failure therapies. At inappropriately low doses, diuretics actually cause fluid retention, which can diminish the response to ACE inhibitors and increase the risk of p-blocker therapy. On the other hand, inappropriately high doses cause volume contraction, which can increase the risk of hypotension with ACE inhibitors and vasodilators, and the risk of renal failure with ACE inhibitors and angiotensin II receptor antagonists.
Even in the absence of data showing clear mortality benefit, diuretics will continue to be used routinely in the management of congestive heart failure for symptomatic relief. They must be combined with ACE inhibitors and P-blockers, both of which have favorable long-term effects on cardiac remodeling and hence on survival.
drug; diuretic; management; symptomatic relief; combination therapy; ACEI; fi-blocker