Heart Failure by Johann Bauersachs Javed Butler & Peter Sandner

Author:Johann Bauersachs, Javed Butler & Peter Sandner
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

4.2 Eplerenone in HFrEF: EPHESUS and EMPHASIS-HF

Eplerenone was investigated in patients with acute MI complicated by HF due to impaired LV systolic dysfunction (LVSD) – the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study, EPHESUS (Pitt et al. 2003). A total of 6,642 patients from 37 countries were randomized within 14 days following the acute MI to either eplerenone 25 mg OD or placebo on top of SoC. After 4 weeks of treatment, the dose was increased to 50 mg OD provided serum potassium levels were within the required range. The mean dose-equivalent of study medication was 42.6 mg in the eplerenone group. Patients had a mean of 64 years with the majority of them receiving SoC including ACEIs/ARBs, beta-blockers, diuretics, and aspirin. After a mean follow-up of 16 months, the primary endpoint, death from any cause or hospitalization for CV events, was significantly reduced by eplerenone (HR 0.87; 95% CI 0.79–0.95; p < 0.002). This reduction was solely attributed to the prevention of sudden cardiac death. Serious hyperkalemia (≥6 mmol/L) was observed in 5.5% of the eplerenone versus 3.9% of the placebo patients (p = 0.002), respectively.

The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), (Zannad et al. 2011) completed the investigation of steroidal MRAs in the HFrEF spectrum by investigating eplerenone in mild symptomatic HF patients. In this trial, 2,737 patients with NYHA class II, an ejection fraction ≤35% and a CV hospitalization within the last 6 months were randomized to eplerenone or placebo. Based on baseline estimated glomerular filtration rate (eGFR), patients were starting with eplerenone 25 mg OD or 25 mg every other day (EOD) with a potential up-titration to the next higher dose level after 4 weeks of treatment. Mean dose at 5 months in the eplerenone group was 39.1 mg. Patients had a mean age of 69 years, being mainly male and having an ischemic heart disease as the leading cause for HF. Approximately half of the patients had a previous HHF at baseline. The majority of the patients received SoC including ACEIs/ARBs as well as beta-blockers. This trial was stopped early (median follow-up 21 months) because of a significant reduction in the primary composite endpoint – death from any cause or HHF – (HR 0.63; 95% CI 0.54–0.74, p < 0.001) for patients being treated with eplerenone. The incidence of severe hyperkalemia (serum potassium >6 mmol/L) was 2.5% versus 1.9% (p = 0.29) for eplerenone versus placebo, respectively.

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