eplerenone and Acute-Disease

Aldosterone is one of the major factors to cause organ damage during an acute phase of heart failure (HF), and many reports have demonstrated that patients with acute decompensated HF (ADHF) have high blood aldosterone concentrations, and the high aldosterone concentrations predict poor prognosis in patients with HF. These findings suggest that eplerenone, an antagonist of aldosterone receptors may provide a new concept and strategy for the treatment of ADHF, protecting the heart and other organs during chronic phases, depending on the restoration of hemodynamic abnormalities.. EARLIER is an event-driven clinical trial with an estimated enrolment of 300 patients hospitalized with ADHF with reduced left ventricular ejection fraction. ADHF includes ischemic or non-ischemic HF, and patients can be enrolled within 72 h after the visit to the hospital. We randomize the patients taking standard therapies for ADHF to the eplerenone and placebo groups. Eplerenone, either 25 or 50 mg, is administered for 6 months in the eplerenone group, and the corresponding placebo is administered in the placebo group on top of the standard care. We set the primary endpoint as the incidence of the composite endpoint (cardiac death or first re-hospitalization due to cardiac disease) 6 months after the enrollment, and also check the quality of life, i.e., exercise capacity and safety features of eplerenone.. EARLIER is a clinical trial of eplerenone targeting ADHF and also the first multicenter investigator-initiated phase III trial in the cardiovascular field in Japan, funded by the Japanese government.

Topics: Acute Disease; Adult; Clinical Protocols; Double-Blind Method; Early Medical Intervention; Eplerenone; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Spironolactone; Young Adult

Several clinical trials have shown that in patients with acute myocardial infarction (MI), statin therapy improves cardiovascular (CV) outcomes, but in these trials patients with acute heart failure (HF) were excluded or only a few were included. In patients with chronic HF, statin therapy does not reduce all-cause or CV mortality. We aimed to assess the association between statin therapy and clinical outcomes in the setting of acute HF with systolic dysfunction complicating acute MI.. We performed a post-hoc analysis in 6632 patients included in the EPHESUS trial. The mean age of patients was 64 years and 71% were male. Overall, 47% of patients had a statin prescribed at baseline. Cox regression models and a secondary analysis using propensity score matching were fit to assess the association between statin prescription and clinical outcomes. During a mean follow-up of 16 ± 7 months, all-cause death occurred in 385 (12%) patients with and in 647 (18%) patients without a statin (P < 0.001). After extensive adjustment, the risk of all-cause death was 20% lower in patients on statin [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.69-0.92, P = 0.001]. This positive association was mostly due to a lower risk of CV death (HR 0.76, 95% CI 0.65-0.88, P = 0.0002). In contrast, statin use was associated with a higher risk of non-CV hospitalizations (HR 1.16, 95% CI 1.02-1.33, P = 0.02).. Our results suggest that patients with acute HF complicating acute MI may benefit from being on statin therapy. Prospective clinical trials are required to validate these findings.

Topics: Acute Disease; Aged; Double-Blind Method; Drug Therapy, Combination; Eplerenone; Female; Heart Failure, Systolic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Propensity Score; Spironolactone; Stroke Volume; Survival Analysis; Treatment Outcome; United States

Although a variety of prognostic tools have been shown to predict rehospitalization and mortality in heart failure patients, their utility in assessing future costs is less clear. We assessed whether health status assessment with the Kansas City Cardiomyopathy Questionnaire (KCCQ) predicts future costs in stable heart failure outpatients with left ventricular dysfunction after myocardial infarction.. We evaluated 12-month cost utilization data from 1516 heart failure outpatients enrolled in the Quality-of-Life Substudy of the Eplerenone Post-Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Multivariable hierarchical models assessed whether the KCCQ (categorized as 0 to <25, 25 to <50, 50 to <75, and 75 to 100) was an independent predictor of future resource use. At baseline, 685 patients (45.2%) had good health status (KCCQ scores > or =75), whereas 510 (33.6%), 262 (17.3%), and 59 (3.9%) had fair (KCCQ, 50 to 74), poor (KCCQ, 25 to 49), and the worst (KCCQ <25) health status, respectively. After multivariable adjustment, compared with patients with good health status, patients with fair health status incurred incremental 1-year costs of $1520 (cost ratio, 1.23; 95% confidence interval, 1.05 to 1.43), whereas patients with poor and the worst health status incurred incremental 1-year costs of $4265 (cost ratio, 1.63; 95% confidence interval, 1.34 to 1.99) and $8999 (cost ratio, 2.34; 95% confidence interval, 1.62 to 3.38), respectively (P<0.0001 for association with KCCQ). Further adjustment for New York Heart Association class led to only partial attenuation of this relationship (P=0.0002).. Health status assessment predicts resource use and costs over the next year in stable heart failure outpatients with left ventricular dysfunction after myocardial infarction.

Topics: Acute Disease; Aged; Cohort Studies; Eplerenone; Female; Follow-Up Studies; Health Care Costs; Health Status; Heart Failure; Humans; Internationality; Male; Middle Aged; Myocardial Infarction; Spironolactone; Survival Rate; Ventricular Dysfunction, Left

Topics: Acute Disease; Diabetes Complications; Drug Administration Schedule; Drug Therapy, Combination; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Spironolactone; Treatment Outcome

Differences in the clinical impacts of the aldosterone receptor antagonists spironolactone and eplerenone in patients with heart failure (HF) are unclear. Among 838 prospectively enrolled patients hospitalized for HF, 90 treated with eplerenone were compared with 90 treated with spironolactone. The primary endpoint was a composite of cardiovascular death and hospitalization. A serial evaluation of the clinical parameters was performed 1 year after discharge. The mean dose of spironolactone was 27 ± 8 mg and of eplerenone was 34 ± 15 mg. During follow-up (mean 594 ± 317 days), primary endpoints occurred in 27 patients in the eplerenone group (30.0%) and 25 patients in the spironolactone group (27.8%). There were no significant intergroup differences in the primary endpoint (log-rank, p = 0.956). Serial changes in left ventricular ejection fraction, serum brain natriuretic peptide, systolic blood pressure, and estimated glomerular filtration rate did not differ significantly between groups. Although gynecomastia in men was common in the spironolactone group (p = 0.018), the discontinuation rates due to adverse events were similar in the two groups (p = 0.135). Subgroup analyses suggested that eplerenone was associated with a lower hazard rate of the primary endpoint in female patients (interaction, p = 0.076). Among patients with HF, eplerenone and spironolactone have similar impacts on cardiovascular outcomes and safety.

Topics: Acute Disease; Aged; Eplerenone; Female; Follow-Up Studies; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Prospective Studies; Spironolactone; Time Factors; Treatment Outcome; Ventricular Function, Left

This study aimed to evaluate the role of eplerenone on the modulation of interleukin (IL)-1β and IL-33/sST2 signaling pathway in an experimental model of left ventricular (LV) systolic dysfunction after acute myocardial infarction (MI). MI rats were randomly assigned to no treatment (MI group, n = 10), to receive eplerenone (Epl group, n = 10), or anakinra (Ana group, n = 10). LV function was assessed by echocardiography. IL-1β, IL-33/sST2, and cardiac fibrosis biomarkers were analyzed by quantitative real-time reverse transcription polymerase chain reaction (PCR). Rats with MI showed significant reduction of LV systolic function, but treatment with eplerenone or anakinra improved left ventricular end-diastolic volume (LVEDV) and LVEDV/mass values. In the infarcted myocardium, compared with sham animals, the MI group had higher level of IL-33, sST2, and IL-1β, as well as higher concentrations of markers of fibrosis and inflammation. Treatment with anakinra downregulated sST2 but with no effects on IL-33. Eplerenone reduced levels of sST2 and IL-1β significantly. Both anakinra and eplerenone treatments were associated with lower levels of fibrosis and inflammatory markers. IL-1β could induce expression of sST2, accelerating the progression of heart failure after acute MI. Eplerenone could improve LV function by reducing expression of IL-1β and sST2.

Topics: Acute Disease; Animals; Antihypertensive Agents; Eplerenone; Interleukin-1beta; Interleukin-33; Male; Myocardial Infarction; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-1; Signal Transduction; Ventricular Dysfunction, Left

Topics: Acute Disease; Catecholamines; Collagen; Eplerenone; Heart Rate; Humans; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Randomized Controlled Trials as Topic; Spironolactone; Treatment Outcome; Ventricular Dysfunction; Ventricular Remodeling