Current evidence supporting the role of diuretics in heart failure: a meta analysis of randomised controlled trials
Introduction
Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide. During the last 2 decades clinical trials have shown that use of angiotensin-converting enzyme (ACE) inhibitors [1], [2], [3], and more recently β-blockers [4], [5] reduce mortality and morbidity in CHF.
Diuretics are regarded as the first-line treatment for patients with CHF since they provide symptomatic relief [6], [7], [8]. Despite widespread clinical acceptance of the use of diuretics, there is uncertainty about their precise therapeutic efficacy because there are no large trials comparable to those of ACE inhibitors [1], [2], [3] and β-blockers [4], [5]. Diuretics reduce pulmonary congestion in patients with heart failure, but their effects on disease progression and survival remain unclear [9], [10]. We conducted a meta-analysis to summarise the current evidence for conventional diuretic therapy in patients with heart failure based on data from published randomised controlled trials to determine whether there were any effects on clinical outcomes.
Section snippets
Methods
Randomised trials of loop or thiazide diuretic therapy in patients with CHF were identified by performing a Medline and Embase search referenced between 1966 and 1999. The search was carried out using the following keywords: heart failure; congestive heart failure; cardiac failure; diuretics; treatment; trials; randomised controlled trials; controlled trials; observational studies and reviews. Hand searching of pertinent journals was carried out and reference lists of papers were inspected. The
Results
Eighteen randomised controlled trials carried out from 1966 to 1999 met our criteria [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33] (Table 1, Table 2). Four studies which did not fulfil our criteria were excluded [12], [13], [14], [15] (Fig. 1). One of these studies was the large RALES trial [15]. This was a double-blind study of the effect of spironolactone vs. placebo on morbidity and mortality in patients with severe heart failure.
Discussion
The principal finding of this systematic overview was that treatment with diuretic therapy produced a relative reduction in mortality of about 70% (absolute reduction of 8%) with wide confidence intervals compared to control in patients with heart failure. If this estimate is correct about 80 deaths could be avoided for every 1000 patients treated. We also demonstrate that diuretic therapy compared to placebo produced a similar reduction in the risk of worsening heart failure. Compared to other
Limitations
This analysis has several limitations. All randomised trials were small with inadequate statistical power to demonstrate clearly the effectiveness of the intervention in terms of reduction in morbidity and mortality rates. There was also great variability in the type of intervention, clinical characteristics of patients, assessment of severity, aetiology of heart failure, study duration, concomitant medications, outcome measures, and drop out rates. The methods of masking and assessment of
Conclusion
Our study provides evidence of the benefits of diuretics on mortality, progression of heart failure and exercise capacity in patients with heart failure. This evidence from trials done is not sufficient by current standards to justify widespread use of diuretics to influence clinical outcomes. On the other hand, clinical experience with diuretics in heart failure following the seminal work of Slater and Nabarro in 1958 [40], provides clinicians with the evidences of experience for continuing to
Acknowledgements
The authors would like to thank Duolao Wang (London School of Hygiene and Tropical Medicine) and Andrew Wright (Clinical Trials and Evaluation Unit) for statistical support.
References (40)
- et al.
Long-term ACE inhibitor therapy in patients with heart failure or left ventricular dysfunction: a systematic overview of data from individual patients
Lancet
(2000) - et al.
The Metoprolol in Dilated Cardiomyopathy (MDC) Study
Lancet
(1993) - et al.
Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in chronic heart failure secondary to coronary artery disease
Am J Cardiol
(1995) - et al.
Symptomatic assessment of patients with heart failure: double-blind comparison of increasing captopril in patients with moderate heart failure
Lancet
(1986) - et al.
Swedish trial in old patients with hypertension (STOP-hypertension)
Lancet
(1991) - et al.
QT dispersion and sudden unexpected death in chronic heart failure
Lancet
(1994) New Engl J Med
(1992)New Engl J Med
(1991)Circulation
(1994)- et al.
Diuretics as essential and sole treatment in chronic heart failure
Cardioscience
(1997)
Untreated heart failure: clinical and endocrine effects of introducing diuretics
Br. Heart J.
Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without heart failure
Circulation
Statistical aspects of the analysis of data from retrospective studies of diseases. Statistical methods for rates and proportion
Acute and chronic effects of a diuretic monotherapy with piretanide in congestive heart failure: a placebo-controlled trial
Cardiovasc. Drugs Ther.
Discontinuation of chronic diuretic therapy in stable congestive heart failure
Am J Cardiol
Effect of spironolactone on morbidity and mortality in patients with severe heart failure
New Eng J Med
The effects of discontinuing long-term diuretic therapy in elderly
Age Ageing
Cited by (200)
Implantable Hemodynamic Monitors Improve Survival in Patients With Heart Failure and Reduced Ejection Fraction
2024, Journal of the American College of CardiologyThe burden of atrial fibrillation and heart failure in hospitalized patients: A real-world survey in a nationwide snapshot
2023, Hellenic Journal of CardiologyHeart failure: pathophysiology and the emergence of novel therapies
2023, Cardiovascular Endocrinology and Metabolism: Theory and Practice of Cardiometabolic MedicineMechanism of action of diuretic and anti-diuretic drugs
2023, How Synthetic Drugs Work: Insights into Molecular Pharmacology of Classic and New PharmaceuticalsPharmacologic Therapy for Heart Failure with Preserved Ejection Fraction
2022, Cardiology ClinicsAlumina catalyst with high density of medium acid sites for N-arylpyrrolidines synthesis
2022, Applied Catalysis A: General