Cochrane for Clinicians
Putting Evidence into Practice
Diuretics for Treatment of Patients with Heart Failure?
Am Fam Physician. 2006 Aug 1;74(3):411-413.
This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). EB CME is clinical content presented with practice recommendations supported by evidence that has been reviewed systematically by an AAFP-approved source. The practice recommendations in this activity are available at http://www.cochrane.org/reviews/en/AB003838.html.
A 60-year-old woman with known heart failure presents with worsening dyspnea and increased lower-extremity edema.
Should diuretics be used for treatment of patients with heart failure?
Compared with other active medications, diuretics can improve exercise capacity in patients with heart failure by about 30 percent. Withdrawal of diuretic therapy from patients with heart failure may increase the risk of hospital readmission or death. About eight deaths are prevented for every 100 patients treated.1
Heart failure affects more than 5 million persons in the United States,2 and loop diuretics have been a standard component of treatment for heart failure since they were introduced in the 1960s. In recent years, there has been growing evidence for the use of other medications in the management of heart failure, including angiotensin-converting enzyme (ACE) inhibitors,3 beta blockers,4 aldosterone antagonists,5 and angiotensin-receptor blockers (ARBs),6 as well as further investigation of the use of digitalis.7 With these advances, the specific benefits of diuretics and their place in the management of heart failure has become less clear.
Guidelines released by the American Heart Association (AHA) and the American College of Cardiology (ACC) in 2005 proposed a staging system to describe the progression of heart failure as a chronic disease and made new recommendations for its medical management using a stage-based assessment of disease severity in individual patients (Table 1). 2 For patients at high risk of developing heart failure (stage A), the guidelines recommend controlling risk factors and using ACE inhibitors or ARBs in patients with vascular disease; for patients who have cardiac structural abnormalities but have never developed clinical heart failure (stage B), the guidelines recommend beta blockers and ACE inhibitors or ARBs, as well as close monitoring for the development of clinical heart failure. Diuretics are recommended for the control of fluid retention in patients with clinical heart failure or a history of heart failure symptoms (stage C), as well as for patients with refractory end-stage heart failure (stage D) who need close attention to fluid balance and control of fluid retention.2
TABLE 1 ACC/AHA Heart Failure Staging System
ACC/AHA Heart Failure Staging System
Patients at high risk of developing heart failure
Patients with cardiac structural abnormalities or remodeling (e.g., left ventricular dysfunction from a prior infarction) who have not developed heart failure symptoms
Patients with cardiac structural abnormalities or remodeling and current or prior symptoms of heart failure
Patients with refractory end‐stage heart failure
ACC = American College of Cardiology; AHA = American Heart Association.
Information from reference 2.
The studies retrieved by this Cochrane review1 mainly were small, older trials, and most used loop diuretics such as furosemide (Lasix). The applicability of their findings to current heart failure management is limited by several factors. First, some of the diuretic studies excluded patients with reduced ejection fractions, whereas current evidence-based recommendations for heart failure management are based on studies of ACE inhibitors, ARBs, and beta blockers in patients with documented systolic dysfunction. One of the diuretic withdrawal trials also excluded patients with a “positive cardiac history” because diuretics were “judged to be mandatory” in these patients. Thus, these studies failed to truly evaluate the necessity of diuretics in patients with more severe clinical heart failure. Second, all the studies were completed before beta blockers became a standard part of recommended heart failure therapy; and third, the three studies that reported mortality all had relatively short follow-up (four, 12, and 52 weeks) and so could not provide data on long-term benefits of diuretic therapy for mortality in heart failure.
Background. Chronic heart failure is a major cause of morbidity and mortality worldwide. Diuretics are regarded as the first-line treatment for patients with congestive heart failure because they provide symptomatic relief. The effects of diuretics on disease progression and survival remain unclear.
Objectives. To assess the harms and benefits of diuretics for chronic heart failure.
Search Strategy. The authors1 searched the Cochrane Central Register of Controlled Trials (Issue 2, 2004), MEDLINE 1966-2004, EMBASE 1980-2004, and HERDIN database. They hand searched pertinent journals and inspected reference lists of papers. They also contacted manufacturers and researchers in the field.
Selection Criteria. Only double-blind, randomized controlled trials of diuretic therapy comparing one diuretic with placebo or one diuretic with another active agent (e.g., angiotensin-converting enzyme [ACE] inhibitors, digoxin) in patients with chronic heart failure were eligible for inclusion.
Data Collection and Analysis. Two reviewers independently abstracted the data and assessed the eligibility and methodologic quality of each trial. Extracted data were entered into the Review Manager version 4.2 computer software and analyzed by determining the odds ratio (for dichotomous data) and difference in means (for continuous data) of the treated group compared with control groups. The likelihood of heterogeneity of the study population was assessed by the chi-square test. If there was no evidence of statistical heterogeneity, and pooling of results was clinically appropriate, a combined estimate was obtained using the fixed-effects model.
Primary Results. The authors included 14 trials (525 participants); seven were placebo controlled, and seven compared diuretics against other agents such as ACE inhibitors or digoxin. The authors analyzed the data for mortality and for worsening heart failure. Mortality data were available in three of the placebo-controlled trials (202 participants). Mortality rates were lower among participants treated with diuretics than among those receiving placebo (odds ratio [OR] for death = 0.24; 95% confidence interval [CI], 0.07 to 0.83; P = .02). Admission for worsening heart failure was reduced in those taking diuretics in two trials (169 participants; OR = 0.07; 95% CI, 0.01 to 0.52; P = .01). In four trials comparing diuretics with active control (91 participants), diuretics improved exercise capacity in participants with chronic heart failure (weighted mean difference = 0.72; 95% CI, 0.40 to 1.04; P < .0001).
Reviewers' Conclusions. The available data from several small trials show that in patients with chronic heart failure, conventional diuretics appear to reduce the risk of death and worsening heart failure compared with placebo. Compared with active control, diuretics appear to improve exercise capacity.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of SystematicReviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the originalreviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minorediting changes have been made to the text (http://www.cochrane.org)
Nevertheless, the review does shed some light on the role of diuretics in the long-term management of heart failure. Three studies showed a reduction in mortality among patients taking diuretics, but most deaths occurred in two trials that studied withdrawal of diuretics from clinically stable patients. Two trials of diuretic withdrawal found lower hospital readmission rates among patients who continued to take diuretics. There also was evidence in active-control and crossover studies that diuretics helped improve exercise capacity. Although the evidence to support the use of diuretics in heart failure management is limited in scope and quality, it is unlikely that there will be any future high-quality, placebo-controlled trials to shed further light on this issue.
Based on the available evidence, it appears safe to conclude that diuretics can improve exercise tolerance for patients with heart failure, and that patients with heart failure who are taking diuretics may be at increased risk of hospital readmission or death if the diuretics are withdrawn. Diuretics should be used for relief of heart failure symptoms, with appropriate use of ACE inhibitors and beta blockers, as well as aldosterone antagonists and digoxin, in line with the AHA/ACC recommendations for treatment of patients with stages C and D heart failure.2
1. Faris R, Flather MD, Purcell H, Poole-Wilson PA, Coats AJ. Diuretics for heart failure. Cochrane Database Syst Rev. 2006;(1):CD003838.
2. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2005;112:e154–235.
3. Flather MD, Yusuf S, Kober L, Pfeffer M, Hall A, Murray G, et al. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet. 2000;355:1575–81.
4. Lee S, Spencer A. Beta-blockers to reduce mortality in patients with systolic dysfunction: a meta-analysis. J Fam Pract. 2001;50:499–504.
5. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341:709–17.
6. Lee VC, Rhew DC, Dylan M, Badamgarav E, Braunstein GD, Weingarten SR. Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction [Published correction appears in Ann Intern Med 2005;142:391]. Ann Intern Med. 2004;141:693–704.
7. Hood WB Jr, Dans AL, Guyatt GH, Jaeschke R, McMurray JJ. Digitalis for treatment of congestive heart failure in patients in sinus rhythm. Cochrane Database Syst Rev. 2004;(2):CD002901.
The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. William E. Cayley, Jr., M.D., M.Div., presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a full critique of the review.
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