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Long-term diuretic use and increased mortality and hospitalization in heart failure

Diuretic use has long been a mainstay in the management of symptomatic heart failure with pulmonary or systemic congestion, or both. Physicians of a certain age may remember when the order "mercuhydrin 2 cc IM" was used for the patient presenting to the emergency department with heart failure, often with pulmonary edema. There were few other choices. Long-term diuretic use with thiazides became common in the latter part of the 20th century, and in the late 1960s and 1970s, loop diuretics, such as furosemide (Lasix), became the diuretics of choice for patients with heart failure and fluid retention. There is little doubt that these potent diuretics have eased the management of this condition, and most patients can now be kept reasonably free of severe edema and pulmonary congestion. For most patients with advanced heart failure, there is no alternative to the use of potent diuretics to manage the symptoms that have the greatest effect on quality of life.

Is there a cost, medically, to this use of long-term potent diuretics? Clearly, excessive diuresis with volume depletion is to be avoided, certainly in the heart failure patient who may need normal or even increased volume to optimize cardiac output via the Starling effect. And the adverse effects of diuretics in patients with renal insufficiency are well recognized, if often difficult to manage.

With the more recent awareness of the critical importance of the neurohormonal aspects of heart failure, we now recognize that diuretics may have deleterious effects on the heart itself. Blood volume contraction, via diuretics or otherwise, stimulates the renin-angiotensin-aldosterone system (RAAS), which in turn stimulates the sympathetic nervous system, resulting in progression in the structural and functional disorder that characterizes heart failure.

In this issue of Cardiology Review, Ahmed presents an analysis of the Digitalis Investigation Group (DIG) trial showing that diuretic use appears to increase the risk of mortality and hospitalization. The investigators used "propensity scores" to compare patients with otherwise similar risk profiles who did or did not take diuretics.

As the author mentions, most of these patients were taking angiotensin-converting enzyme (ACE) inhibitors, which would be expected to ameliorate at least some of the adverse effects of RAAS stimulation by diuretics. Most were not taking beta blockers, which had not yet become standard treatment for heart failure when the DIG trial was undertaken. Nor were they taking aldosterone inhibitors, which have since become widely used for severe heart failure and for heart failure occurring with acute myocardial infarction. As the author is careful to mention, the study was not a prospective randomized trial, and thus, a further difference between the 2 groups, those without and those with diuretic use may have escaped the analysis.

What is one to make of this study regarding the treatment of patients? Several lessons may be drawn. Diuretic use on a daily basis should be reserved for those patients who truly need it. It is better to individualize diuretic dosage, especially for those patients who may retain fluid only occasionally. Indeed, weight-based administration of diuretics is a successful strategy in many patients with class I or class II heart failure. Even the more severely symptomatic patient can use dose adjustment based on weight to avoid the daily use of the most potent regimen. In addition, it would appear likely that the worst effects of neurohormonal stimulation by diuretics can be antagonized by use of ACE inhibitors or angiotensin receptor blockers, or both; beta blockers; and at least in selected cases, aldosterone antagonists.

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