Use of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction
- Wilson S Colucci, MD
Wilson S Colucci, MD
- Section Editor — Heart Failure
- Professor of Medicine
- Boston University School of Medicine
- Marc A Pfeffer, MD, PhD
Marc A Pfeffer, MD, PhD
- Dzau Professor of Medicine
- Harvard Medical School
- Brigham and Women’s Hospital
- Section Editors
- Stephen S Gottlieb, MD
Stephen S Gottlieb, MD
- Section Editor — Heart Failure
- Professor of Medicine
- University of Maryland School of Medicine
- Richard H Sterns, MD
Richard H Sterns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Professor of Medicine
- University of Rochester School of Medicine and Dentistry
Mineralocorticoid receptor antagonist (MRA) therapy is one component of treatment of patients with systolic heart failure (HF) . Clinical trials have demonstrated that MRA therapy reduces morbidity and mortality in patients with HF due to left ventricular systolic dysfunction.
The indications, efficacy, risks, and mechanisms of benefit of MRA therapy in systolic HF will be reviewed here. Overall management of systolic HF and use of MRAs in patients with diastolic HF are discussed separately. (See "Overview of the therapy of heart failure with reduced ejection fraction" and "Treatment and prognosis of heart failure with preserved ejection fraction".)
MECHANISMS OF ACTION
Two major, not mutually exclusive mechanisms may contribute to the benefits associated with mineralocorticoid receptor antagonist (MRA) therapy in patients with systolic heart failure (HF): maintenance of a higher serum potassium concentration via reduced urinary potassium loss, and blockade of the deleterious effects of aldosterone on the heart. To the degree that the latter effect is important, a similar benefit would not be expected with other potassium-sparing diuretics (such as amiloride).
Raising serum potassium — Mineralocorticoid receptor antagonism may preserve serum potassium concentration and thus counter the risk of hypokalemia and associated arrhythmic risk caused by non-potassium-sparing diuretics. Support for this mechanism comes from observation of increased arrhythmic mortality in patients with HF treated with non-potassium-sparing diuretics alone in a retrospective analysis of data from the SOLVD trial . In this study of data from 6797 patients with symptomatic New York Heart Association (NYHA) (table 1) class II to III HF and a left ventricular ejection fraction (LVEF) less than 36 percent, diuretic use, compared to no diuretic use, was associated with a higher incidence of overall mortality, cardiovascular deaths (11.4 versus 4.6 percent per year), and arrhythmic or sudden death. The risk of arrhythmic death associated with the use of non-potassium-sparing diuretics was significantly elevated (relative risk 1.33) after controlling for disease severity, comorbid illnesses, and concomitant medications, including angiotensin converting enzyme (ACE) inhibitors. In comparison, there was no association between arrhythmic death and use of a potassium-sparing diuretic, either alone or in combination with a non-potassium-sparing agent.
MRA therapy reduced the risk of hypokalemia in patients with systolic HF in clinical trials (eg, in the EPHESUS trial, serum potassium <3.5 mEq/L occurred in 8.4 with eplerenone versus 13.1 percent with placebo) [3,4]
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- MECHANISMS OF ACTION
- Raising serum potassium
- Blocking aldosterone effect on the heart
- Effect of concurrent ACE inhibitors
- OUR APPROACH
- Selection of patients
- Choice of agent
- Timing of initiation
- Class III or IV heart failure
- Class II heart failure
- Post-myocardial infarction with heart failure and/or diabetes
- Combination with other HF medications
- ADVERSE EFFECTS
- Risk of hyperkalemia
- - Effect of renal dysfunction
- - Clinical usage and risk of hyperkalemia
- Adverse endocrine effects
- MAJOR SOCIETY GUIDELINES
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS