Advances in Heart Failure Loop Diuretics in Acute Decompensated Heart Failure Necessary? Evil? A Necessary Evil?

Acute decompensated heart failure (ADHF) is the most common cause of hospital admission in patients 65 years, accounting for 1 million hospitalizations, 6 million hospital days, and $12 billion in costs annually in the United States alone.1,2 The prognosis of patients admitted with ADHF is dismal, with rates of rehospitalization or death approaching 50% within 6 months.3,4 Despite these alarming and oft-cited statistics, the development of new therapies in ADHF has changed little over recent decades,5 and short-term and intermediate-term outcomes have remained poor.6 In addition to spurring the development of new therapies for ADHF, these data suggest the need for an active reappraisal of current therapy. This review will focus on the data (or lack thereof) supporting the efficacy and safety of loop diuretics in ADHF, discuss the challenges in performing clinical trials of diuretics in ADHF, and describe an ongoing clinical trial designed to rigorously evaluate optimal diuretic use in this syndrome. Loop diuretics are the foundation of current ADHF therapy. Data from the ADHF National Registry demonstrate that approximately 90% of patients hospitalized with ADHF in the United Sates receive IV loop diuretics during the hospitalization.7 This nearly ubiquitous use of loop diuretics in ADHF is understandable given that the majority of ADHF hospitalizations are related to volume overload and congestion,8 and decades of clinical observation has shown that IV administration of loop diuretics results in prompt diuresis and relief of symptoms in most patients. Despite this breadth of clinical experience, however, high quality data supporting the safety and efficacy of loop diuretics in ADHF are sparse. Accordingly, the most recent practice guidelines for ADHF from the Heart Failure Society of America recommend loop diuretics at “doses needed to produce a rate of diuresis sufficient to achieve an optimal volume status.”9 Notably, this guideline has the strongest level of recommendation (is recommended) but the lowest level of evidence (C, based on expert opinion only). Current guidelines from the American College of Cardiology and the American Heart Association do not address the treatment of ADHF.10 Although modern phase II development programs for new drugs go to great lengths to identify the range of doses that best balance safety and efficacy, these fundamental clinical questions have not been rigorously investigated for loop diuretics. Given the lack of available evidence to guide diuretic therapy, it is not surprising that practice patterns vary widely between physicians and centers. In a study identifying unanswered questions in heart failure management, 50% of the questions were related to the most appropriate use of diuretics.11