The effect of eplerenone vs. placebo on cardiovascular mortality

August 29, 2011, European Society of Cardiology

Today results from a new sub-analysis of the EMPHASIS-HF study showed significant reductions in death and hospitalization for five pre-defined high-risk patient sub-groups with chronic heart failure (CHF) and mild symptoms treated with eplerenone in addition to standard therapy versus those treated with placebo and standard therapy.

Commenting on the findings presented for the first time during the Congress (ESC) Hot Line Session on 29th August 2011, EMPHASIS-HF investigator Professor Bertram Pitt, Division of Cardiology, University of Michigan School of Medicine, U.S., said: "The 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 (CV mortality/hospitalization for HF) over an additional 7 months of follow up on douBle blind TherApy in #Onjunction with the prior benefi#iaL requLts fr/m EPHESUS presents compelling evidence for the use of eplerenone in patients with systolic chronic HF NYHA class II and mild symptoms."

Eplerenone has been shown to reduce the primary endpoint of or hospitalization for (CV mortality/Hosp.HF ), as well as total mortality, total hospitalizations, and new onset atrial fibrillation/flutter in patients with NYHA class II chronic (NEJM 2011;364:11-21-and ESC-HF 2011). To further determine the applicability of these results to clinical practice the efficacy and safety of eplerenone 25-50 mg/day was evaluated in 5 pre-specified high-risk subgroups including: Age > 75 years, (DM), estimated (eGFR) < 60 ml/min /1.73 m2, Left ventricular ejection fraction (LVEF) < 30 %, and Systolic blood pressure ( SBP) < median of 123 mm Hg.

Results – primary endpoint-for high-risk patient subgroups

In patients > 75 years of age 78 (23.6%) of 330 patients on eplerenone and 107 (32.7%) of 327 on placebo had a primary endpoint - Hazard ratio (HR) 0.66, p<0.004, 95% Confidence Intervals (CI ) 0.49-0.88.

In patients with history of diabetes 99 (21.6%) of 459 on eplerenone and 141 (35.2%) of 400 on placebo had primary endpoint - HR 0.54, p= <0.0001, (CI) 0.42-0.70.

In patients with eGFR< 60 ml/min /1.73 m2 107 (24.4%) of 439 on eplerenone and 163 (34.5%) of 473 on placebo had a primary endpoint - HR 0.62, p=0.0001, CI 0.49-0.79.

In patients with a LVEF <30% 180 (19.3%) of 934 patients on eplerenone and 267 (27.3%) of 978 on placebo had a primary endpoint - HR 0.65, p<0.0001, CI 0.53-0.78.

In patients with a SBP< median 123 mm Hg 138 (20.6%) of 669 patients on eplerenone and 201 (29.4 %) of 683 on placebo had a primary endpoint –HR 0.63, p=<0.0001, CI 0.51-0.79.

No new safety information emerged as a result of this analysis. In each of these high risk subgroups patients receiving eplerenone had a significant increase (p<0.05) in the incidence of hyperkalaemia (K+> 5.5 mmol/l). However, there was no significant increase in serious hyperkalemia (K+>6.0 mmol/l), hyperkalaemia leading to drug discontinuation, hospitalization for hyperkalemia, or hospitalization for worsening renal function.

Importantly, after the trial was prematurely stopped for efficacy on March 25, 2010 (primary endpoint [CV mortality and HF hospitalization] – HR 0.63, p< 0.0001, CI 0.54-0.74) additional primary endpoints were observed while patients remained on double blind therapy over an additional mean 7 months of follow up (primary endpoint - HR 0.66 , p< 0.0001 CI 0.57-0.77). This new sub-analysis further demonstrated that the beneficial effect of eplerenone remained significant across the wider study population over the additional follow-up period.

Results – secondary endpoints

In the five pre-specified high risk groups, the key secondary endpoints of all-cause hospitalization and HF hospitalization, achieved statistically significant (p<0.01) relative risk reductions for the eplerenone group compared to the placebo group.

Explore further: EMPHASIS HF: Study shows epleronone to reduce atrial fibrillation

Related Stories

EMPHASIS HF: Study shows epleronone to reduce atrial fibrillation

May 22, 2011
The aldosterone antagonist eplerenone (Inspra, Pfizer) significantly reduced the development of new onset atrial fibrillation and flutter (AFF) in patients with class 2 heart failure, concludes a sub-analysis of the EMPHASIS-HF ...

Sexual health of men with chronic heart failure significantly improves with CRT

June 2, 2011
A new study published in the journal Clinical Cardiology reveals that in men with chronic heart failure, cardiac resynchronization therapy (CRT) improves patients' libido, erectile dysfunction, and sexual performance.

Telemonitoring can improve overall survival of HF patients

May 22, 2011
Two trials presented at the Heart Failure Congress 2011, organized by the Heart Failure Association of the European Society of Cardiology (HFA of the ESC), will help to define the precise populations of patients with chronic ...

Recommended for you

Eating yogurt may reduce cardiovascular disease risk

February 15, 2018
A new study in the American Journal of Hypertension, published by Oxford University Press, suggests that higher yogurt intake is associated with lower cardiovascular disease risk among hypertensive men and women.

Newly discovered gene may protect against heart disease

February 14, 2018
Scientists have identified a gene that may play a protective role in preventing heart disease. Their research revealed that the gene, called MeXis, acts within key cells inside clogged arteries to help remove excess cholesterol ...

Blood thinners may raise stroke risk in over-65s with kidney disease

February 14, 2018
People over 65 years old may be increasing their stroke risk by taking anticoagulants for an irregular heartbeat if they also have chronic kidney disease, finds a new study led by UCL, St George's, University of London and ...

Cardiac macrophages found to contribute to a currently untreatable type of heart failure

February 14, 2018
A team of Massachusetts General Hospital (MGH) investigators has discovered, for the first time, that the immune cells called macrophages contribute to a type of heart failure for which there currently is no effective treatment. ...

Study maps molecular mechanisms crucial for new approach to heart disease therapy

February 13, 2018
Creating new healthy heart muscle cells within a patient's own ailing heart. This is how scientists hope to reverse heart disease one day. Today, a new study led by UNC-Chapel Hill researchers reveals key molecular details ...

Quality toolkit improves care in Indian hospitals

February 13, 2018
A simple toolkit of checklists, education materials and quality and performance reporting improved the quality of care but not outcomes in hospitals in the south Indian state of Kerala and may have the potential to improve ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.