Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Jump to navigation Jump to search

WikiDoc Resources for Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Articles

Most recent articles on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Most cited articles on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Review articles on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Articles on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Images of Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Photos of Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Podcasts & MP3s on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Videos on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Evidence Based Medicine

Cochrane Collaboration on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Bandolier on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

TRIP on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Clinical Trials

Ongoing Trials on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study at Clinical Trials.gov

Trial results on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Clinical Trials on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

NICE Guidance on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

NHS PRODIGY Guidance

FDA on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

CDC on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Books

Books on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

News

Eplerenone Post-Ami Heart Failure Efficacy And Survival Study in the news

Be alerted to news on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

News trends on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Commentary

Blogs on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Definitions

Definitions of Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Patient Resources / Community

Patient resources on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Discussion groups on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Patient Handouts on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Directions to Hospitals Treating Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Risk calculators and risk factors for Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Healthcare Provider Resources

Symptoms of Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Causes & Risk Factors for Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Diagnostic studies for Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Treatment of Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Continuing Medical Education (CME)

CME Programs on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

International

Eplerenone Post-Ami Heart Failure Efficacy And Survival Study en Espanol

Eplerenone Post-Ami Heart Failure Efficacy And Survival Study en Francais

Business

Eplerenone Post-Ami Heart Failure Efficacy And Survival Study in the Marketplace

Patents on Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Experimental / Informatics

List of terms related to Eplerenone Post-Ami Heart Failure Efficacy And Survival Study

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Acronym

EPHESUS stands for Eplerenone Post-AMI Heart Failure Efficacy and Survival Trial.

Background

Eplerenone is an aldosterone antagonist that blocks the mineralocorticoid receptor. In contrast to spironolactone, it does not block the glucocorticoid, progesterone, or androgen receptors and for that reason it may may be associated with fewer side effects than spironolactone. Pre clinical studies have demonstrated that aldosterone antagonism may improve ventricular remodeling and collagen formation among patients who sustain LV dysfunction following an MI.

The EPHESUS study builds upon the RALES study (Randomized Aldactone Evaluation Study) which demonstrated that aldosterone inhibition with the older agent spironolactone reduced mortality when added to an ACE inhibitor among patients with severe congestive heart failure. In the older RALES study, only 10% of patients were on a beta blocker, and the benefit of an aldosterone antagonist on top of beta blockade was not adequately tested.

Methods

Entry criteria included a left ventricular ejection fraction <40% a range of 3 to 14 days following MI (median = 7 days). Diabetics required only a LVEF < 40%. Patients (n=6632) were randomized to administration of either eplerenone at a starting dose of 25 mg (titrated to a maximum of 50 mg q day, mean dose 43 mg) versus placebo. Exclusion criteria included a baseline K+ of > meq/li and a baseline Cr of > 2.5 mg/dl. This was an event driven trial that was continued until there were 1012 deaths. There was a median of 16 months of follow-up.

Results

All cause death, and cardiovascular death, and cardiovascular death plus rehospitalization were all significantly reduced over 16 months of follow-up.


End point

Eplerenone, No. (%)

Placebo, No. (%)

Relative risk (95% CI)

p

Mortality (Prim Endpt) 478 (14.4) 554 (16.7) 0.85
(0.75-0.96)
0.008
Cardiovascular mortality 407 (12.3) 483 (14.6) 0.83
(0.72-0.94)
0.005
CV mortality or hospitalization for CV events* 885 (26.7) 993 (30.0) 0.87
(0.79-0.95)
0.002

Sudden death from cardiac causes was reduced (p=0.03). Among those patients who would qualify for an AICD by MADIT II criteria (an LVEF <30%), there was a 33% reduction in sudden cardiac death. When the analysis was restricted to those patients who were treated with optimal evidence based therapy with an ACE/ARB, aspirin, statin, beta-blockade and reperfusion therapy there was still a 26% reduction in all cause mortality.

Number Needed to Treat (NNT) = 50 patients to save one life, and 33 to prevent one cardiovascular death or rehospitalization.

Adverse Events

As might be expected from an aldosterone inhbitor, the risk of hyperkalemia was significantly increased among those patients with a Cr clearance < 50 cc / minute on entry into the trial. There were no deaths attributable to hyperkalemia. As a result, potassium levels should be monitored in patients on eplerenone. Interestingly, the risk of hypokalemia was actually twice as high as the risk of hyperkalemia. It is notable that eplerenone reduced the risk of hypokalemia. The investigators hypothesized that reducing the risk of hypokalemia was important in so far as the presence of hypokalemia reversed any benefit from antihypertensive therapy in the SHEP trial.

Summary

Among MI patients with LV dysfunction, the administration of eplerenone (Inspra®, Pharmacia) in addition to evidence based therapy is associated with a 15% reduction in all cause mortality. In addition, cardiovascular death, and CV death and hospitalization were also significantly reduced.

References