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Adding eplerenone to standard therapy reduces the incidence of new onset atrial fibrillation / flutter in patients with systolic heart failure, sub-analysis of new study shows
- Study also reveals that eplerenone reduces risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms
Singapore, 13 September 2011 - The pre-specified sub-analysis of a new study, eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)1 showed that eplerenone, when added to standard recommended therapy, significantly reduced the incidence of new onset atrial fibrillation (AF) & atrial flutter (AFL) in patients with systolic heart failure and mild symptoms compared with placebo plus standard therapy.
The EMPHASIS-HF trial enrolled 2,737 subjects with chronic systolic heart failure (NYHA class II) and mild symptoms. The sub-analysis looked at subjects without a history of AF/AFL based on the baseline ECG and physical examination (911 in the eplerenone group and 883 in the placebo group). New onset AF/AFL occurred in 25 (2.7%) patients in the eplerenone group versus 40 (4.5%) patients in the placebo group.2
Eplerenone reduces risk of death and hospitalization
The latest findings add to the already positive results of the EMPHASIS-HF trial published in the New England Journal of Medicine. Eplerenone, an aldosterone antagonist, had proven to be effective in reducing the risk of death or hospitalizations due to heart failure. The promising results have led its maker, Pfizer, to make the drug available in Singapore.
The results showed that eplerenone in comparison to placebo produced a 37% reduction in the primary end point of the composite of death from cardiovascular causes or hospitalization for heart failure, a 24% reduction in cardiovascular death, and a 42% reduction in hospitalization for heart failure for patients with class II or mild heart failure.
Aldosterone antagonists have long been a mainstay in the treatment regimen of those with moderate to severe heart failure. However, according to Dr Bernard Kwok, Consultant Cardiologist from Mount Elizabeth Medical Centre, and President of the Singapore Cardiac Society, “The results of this study indicate that eplerenone should be extended to a larger population of those suffering from systolic heart failure. Those who have been diagnosed with mild heart failure also stand to benefit from this treatment.”
Heart failure may be caused by several factors including myocardial infarctions and hypertension. In Singapore, 7,143 new cases of acute myocardial infarctions were seen in 2008 alone3. While the latest 2010 National Health Survey has revealed that almost one in four Singaporeans suffer from hypertension.4
Results consistent for sub-analysis of pre-defined high-risk patient sub groups
A new sub analysis of EMPHASIS-HF was presented at the recent European Society of Cardiology Congress (ESC) Hot Line Session5 held in Paris, France. The results show a consistency of the efficacy and safety of eplerenone in addition to standard therapy on pre-specified “high-risk subgroups” and the persistence of a significant beneficial effect on the primary endpoint. These pre-specified high-risk sub groups are: Age > 75 years, Diabetes Mellitus (DM), estimated glomerular filtration rate (eGFR) < 60 ml/min /1.73 m2, Left ventricular ejection fraction (LVEF) < 30%, and Systolic blood pressure (SBP) < median of 123 mm Hg.
“These latest findings may make a difference in the way we treat heart failure. It is clear that under treatment can be avoided by considering the addition of eplerenone to all heart failure regimens. In addition to reducing risk of death and hospitalization it may reduce the incidence of AF/AFL in heart failure patients. AF/AFL is a serious condition which increases complications rates in patients with heart failure," added Dr Kwok.
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About the EMPHASIS-HF trial
EMPHASIS HF (A6141079) is a phase 3B, multinational (2,737 patients from 272 centres in 29 countries), randomized, double-blind placebo-controlled, parallel-group trial. It was conducted in patients with chronic systolic heart failure with mild symptoms (NYHA II) and ejection fraction ≤30% or ≤35% if QRS duration >130msecs, which is a distinct population from the EPHESUS study5 population (patients with left ventricular dysfunction - LVEF ≤ 40 % - and clinical evidence of heart failure after recent myocardial infarction).
The primary objective of this trial was to evaluate the efficacy and safety of eplerenone plus standard heart failure (HF) therapy - including an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin receptor blocker (ARB), plus a beta–blocker – versus placebo plus standard HF therapy on the cumulative incidence of cardiovascular (CV) mortality and HF hospitalization (a composite primary endpoint). The mean follow-up time was 21.1 months.
Patients were randomized (1:1) to receive eplerenone 25 mg once daily (OD) or matching placebo. At four weeks, the dose of study drug could be increased to 50 mg OD (two 25mg tablets of eplerenone or two matching placebo tablets once daily) based on serum potassium level. The trial was designed to enroll 3,100 patients and to continue until a total of 813 adjudicated primary endpoint events were reported.
In May 2010, Pfizer announced that it would halt recruitment to the EMPHASIS-HF trial early on the recommendations of the trial’s independent Executive Steering Committee (ESC). The recommendations followed a second interim analysis by the independent Data Safety Monitoring Committee (DSMC) of the EMPHASIS-HF trial confirming the study has reached its primary efficacy endpoint early according to the protocol pre-defined stopping rules.
The results of the EMPHASIS study were published in 2010. The study was funded by Pfizer.
About Eplerenone
Eplerenone is a steroid nucleus-based mineralocorticoid receptor (MR) antagonist with a higher degree of selectivity than spironolactone. Eplerenone is thought to be a more selective blocker at the mineralocorticoid receptor since there is evidence that some of the effects result from a blockade of cortisol stimulation of the MR-receptor.
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- Zannad F, McMurray JJV, Krum H, et al. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. New England Journal of Medicine. 2011;364:11-21.
- Swedberg K, Zannad F, Krum H et al. Eplerenone reduces the incidence of new onset atrial fibrillation/flutter in patients with systolic heart failure [abstract]. Presented at ESC Heart Failure 2011, Gothenburg.
- 11.02.11, National Registry of Diseases Office, Information paper on acute myocardial infarction in Singapore,2007-2008, Retrieved 26.07.11
- 26 November 2010. Diabetes rate in Singapore rises to a 12-year high. Singapore Government News. Retrieved 28.04.11
- Pitt B et al, Emphasis-HF: The effect of eplerenone versus placebo on cardiovascular mortality or heart failure hospitalization in subjects with NYHA class II chronic systolic heart failure: An analysis of the “high-risk groups. Presented at ESC Hot Line Session 29th August 2011, Paris.