Ephesus

50 %
50 %
Information about Ephesus

Published on October 16, 2016

Author: IsabellaLai

Source: slideshare.net

1. EPHESUS OVMC LANDMARK TRIALS SERIES Pitt B, et al. "Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction". The New England Journal of Medicine. 2003. 348(14):1309-21.

2. 2003 Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)

3. BACKGROUND  The RALES and EMPHASIS-HF trials showed that aldosterone antagonists reduced mortality in heart failure patients with reduced EF (HFrEF)  Mechanism of Aldosterone blockade for Mortality:  Likely through preventing ventricular remodeling and collagen formation in patients with LV dysfunction after MI  Eplerenone is an aldosterone blocker that selectively blocks mineralocorticoid NOT glucocorticoid receptors  Benefit over Spironolactone is lower rates of Gynecomastia  However, it is unknown if post-acute MI, the role of aldosterone antagonist can still apply

4. CLINICAL QUESTION After a patient has an acute MI complicated by HFrEF <40%, does addition of epelrenone (aldosterone antagonist) help reduce mortality?

5. DESIGN  Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial  N=6,642  Eplerenone (n=3,313)  Placebo (n=3,319)  Setting: 674 centers in 37 countries  Enrollment: 1999-2001  Median follow-up: 16 months  Primary outcomes:  All-cause mortality  CV mortality or hospitalization for CV events

6. POPULATION Inclusion Criteria  MI in prior 3-14 days  LVEF <40%  HF (defined as pulmonary crackles, CXR with pulmonary venous congestion, or S3 heart sound)  No symptoms required in diabetic patients Exclusion Criteria  Use of potassium-sparing diuretics  Creatinine >2.5 before randomization  Serum potassium >5 before randomization

7. INTERVENTIONS  Randomized to a group:  Eplerenone  25mg for 4 weeks  Then, if tolerated, 50mg qday, HOLD for hyperkalemia >5.5  Placebo  All patients received optimal medical therapy, including ACE inhibitors, ARBs, diuretics, beta- blockers, and coronary revascularization

8. BOTTOM LINE Among patients with acute MI complicated by LV dysfunction with reduced EF<40%, the addition of eplerenone to optimal medical therapy showed a 15% REDUCTION in morbidity and mortality by

9. CRITICISMS  This study was funded by Pharmacia, the makers of Inspra (Eplerenone)  Beta-blockers was established as the standard of care and used widely during the study period, as opposed to when RALES study was performed (RALES study only showed 10% improvement in benefits)  The RALES trial used Spironolactone. The cost of Eplerenone is significantly higher.

10. DISCUSSION QUESTIONS  What is the benefit of Eplerenone over Spironolactone? Disadvantage?  How is the EPHESUS Trial different than the RALES trial?  According to the EPHESUS trial, in patients after an acute MI, should aldosterone antagonist be started? If so, when?

11. DISCUSSION QUESTIONS/ANSWERS  What is the benefit of Eplerenone over Spironolactone? Disadvantage?  ANSWER:  Benefit: Lower rates of Gynecomastia  Cost: Eplerenone is more expensive  How is the EPHESUS Trial different than the RALES trial?  ANSWER: The RALES trial showed that aldosterone blockade reduces mortality in severe systolic heart failure. The EPHESUS trial showed that mineralcorticoid antagonist after an acute MI is beneficial  According to the EPHESUS trial, in patients after an acute MI, should aldosterone antagonist be started? If so, when?  ANSWER: Yes, Aldosterone antagonist should be started in patients after an acute MI if HFrEF is present (LVEF <40%)

12. BOARD-LIKE QUESTION A 61 yo women, with hx DM2, HTN, HLD, is 5 days s/p DES in LAD for STEMI For the past few days, she is chest pain free. Meds include Aspirin 81, Ticagrelor, Metoprolol, Lisinopril, atorvastatin, and sublingual nitroglycerin PRN. Physical examination: HR 78, BP 121, 72. BMI 22. Lungs clear Heart: RRR, normal S1/S2, no S3/S4/gallops/murmurs Labs: K 4.5, Creatinine 1.7 (baseline) Echo: LVEF 25% (ADAPTED from MKSAP 17) QUESTION Which of the following is the most appropriate adjustment to his discharge medications? A. Get repeat Echo is 3 months B. Add Eplerenone C. Increase Metoprolol D. Start Clopidogrel and stop Ticagrelol E. No Changes

13. BOARD-LIKE QUESTION Educational Objective: How to manage patients post-ACS and PCI. Key Point: - Optimal medical therapy: Lifestyle changes and pharmacologic therapy -- Aspirin, BB, ACEi, Statin. Additionally, post-PCI patients should be on a P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) for at least 1 year - Aldosterone antagonist to be added in patients with reduced EF <40% after MI; however, <35% if has HFrEF not post MI. - This patient’s EF is reduced so Eplerenone should be started ANSWER Which of the following is the most appropriate adjustment to his discharge medications? A. Get repeat Echo is 3 months B. Add Eplerenone C. Increase Metoprolol D. Start Clopidogrel and stop Ticagrelol E. No Changes

14. AHA/ACCF HEART FAILURE RECOMMENDATIONS  Aldosterone antagonists recommended if NYHA class II-IV, LVEF ≤35% unless contraindicated (class I, level A)  If NYHA class II, should have prior CV hospitalization or elevated BNP (or analogous test)  Aldosterone antagonists recommended after MI if LVEF ≤40% with HF symptoms or DM unless contraindicated (class I, level B)  Aldosterone antagonists harmful if creatinine >2.5 mg/dL in men or >2.0 mg/dL in women (GFR <30 mL/min/1.73 m2) or potassium ≥5.0 mEq/L (class III, level B)

Add a comment