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Eplerenone: new drug. Recent myocardial infarction with heart failure: a spironolactone me too
Insights
Spironolactone is preferred for heart failure due to better efficacy and lower hyperkalemia risk compared to eplerenone. Eplerenone may benefit select patients with recent myocardial infarction and heart failure.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Heart failure diagnosis relies on clinical symptoms and cardiac function evaluation, with left ventricular dysfunction defined by ejection fraction <40%.
- Established treatments for chronic heart failure include ACE inhibitors, diuretics, beta-blockers, and spironolactone, with spironolactone demonstrating significant mortality reduction in trials.
- Eplerenone, a spironolactone derivative, is indicated for left ventricular dysfunction post-myocardial infarction.
Purpose of the Study:
- To evaluate the efficacy and safety of eplerenone in patients with heart failure and recent myocardial infarction.
- To compare the clinical outcomes of eplerenone versus spironolactone in heart failure management.
Main Methods:
- The EPHESUS study, a double-blind, placebo-controlled trial, assessed eplerenone's effect on overall mortality in 6632 patients with heart failure and recent myocardial infarction.
- Indirect comparisons of available data were used to assess eplerenone versus spironolactone efficacy and safety profiles.
- Cost-effectiveness analysis was considered, with eplerenone being significantly more expensive than spironolactone in France.
Main Results:
- Eplerenone significantly reduced overall mortality in heart failure patients post-myocardial infarction (16.7% vs. 14.4%, p=0.008), primarily due to early treatment effects.
- Severe hyperkalemia was frequent with eplerenone (5.5%), with increased risk in renal failure and concurrent use of potassium-sparing agents.
- Indirect comparisons favored spironolactone for better efficacy and a lower risk of hyperkalemia in heart failure patients post-myocardial infarction.
Conclusions:
- Spironolactone remains the preferred treatment for heart failure with dyspnea despite standard therapy, offering superior efficacy and safety.
- Eplerenone may have a role in managing non-severe heart failure following recent myocardial infarction.
- Further head-to-head trials are needed to directly compare eplerenone and spironolactone.
Abstract:
(1) Heart failure is diagnosed on the basis of both clinical symptoms and evaluation of cardiac function (preferably measured by echocardiography). Left ventricular dysfunction is defined as a left ventricular ejection fraction (LVEF) below 40%. The drugs of choice for chronic heart failure are certain angiotensin-converting-enzyme (ACE) inhibitors, some diuretics, some betablockers, and spironolactone. In one trial, spironolactone greatly reduced mortality at 24 months (35%, compared with 46% on placebo, p <0.001). (2) Eplerenone, a spironolactone derivative, is marketed for the treatment of left ventricular dysfunction in heart failure patients with recent myocardial infarction. (3) The EPHESUS study, a double-blind, placebo-controlled trial involving 6632 patients, showed a significant reduction in the overall mortality rate among patients with heart failure and recent myocardial infarction treated with eplerenone for 16 months (16.7% versus 14.4%; p = 0.008). This improvement was mainly due to a reduction in mortality during the first month of treatment. Eplerenone has not been compared with spironolactone, although the latter was known to be effective before the EPHESUS trial was conducted. (4) Severe hyperkalemia is frequent with eplerenone, occurring in 5.5% of patients. The risk of hyperkalaemia increases with renal failure and co-administration of potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists and nonsteroidal antiinflammatory drugs. (5) In the short term, the incidence of gynecomastia in patients taking eplerenone seems to be low. (6) In patients who develop heart failure after myocardial infarction, an indirect comparison of available data favours spironolactone over eplerenone (better efficacy, lower risk of hyperkalemia). (7) In France, treatment with eplerenone is about 9 times more expensive than spironolactone. (8) Spironolactone remains the treatment of choice for patients with heart failure and incapacitating dyspnea despite ACE inhibitor and diuretic therapy. Eplerenone may possibly be useful for patients who have non severe heart failure after recent myocardial infarction.
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