eplerenone and Aortic-Valve-Stenosis

The aim of the study is to determine whether the selective aldosterone-receptor antagonist eplerenone delays onset of left ventricular (LV) systolic dysfunction or reduces LV hypertrophy in asymptomatic patients with moderate to severe aortic stenosis. Effects of eplerenone on LV diastolic function and progression of valve stenosis were also evaluated.. Sixty-five asymptomatic patients with a peak aortic valve velocity >3.0 m/s and normal LV function were randomized double blind to eplerenone, 100 mg daily (n = 33), or placebo (n = 32) for a median of 19 (interquartile range 15 to 25) months. Cardiac magnetic resonance imaging and echocardiography were performed and N-terminal pro-brain natriuretic peptide was measured at baseline and follow-up.. Symptomatic deterioration occurred in 13 subjects randomized to eplerenone and 11 to placebo (P = .34). Change in LV mass index (mean change +/- SD -0.3 +/- 14.6 vs +5.1 +/- 15 g/m(2) per year, P = .3), LV ejection fraction (+0.0% +/- 5.7% vs +0.8% +/- 5.7% per year, P = .9), and LV end-systolic volume index (-1.2 +/- 9 vs +0.04 +/- 12 mL/m(2) per year, P = .8) were small and similar for patients randomized to eplerenone and placebo, respectively. Decrease of aortic valve area (-0.11 +/- 0.22 vs -0.18 +/- 0.24 cm(2)/y, P = .2), worsening of LV diastolic dysfunction by echo-Doppler (E/E' +0.49 +/- 0.7 vs +1.32 +/- 2.0/year, P = .4), increase in the plasma level of N-terminal pro-brain natriuretic peptide (+63% vs +12% per year, P = .1), and decline in physical function score (9 +/- 34 vs 12 +/- 37/year, P = .7) were similar for subjects randomized to eplerenone and placebo, respectively.. In asymptomatic patients with moderate-severe aortic stenosis, eplerenone did not slow onset of LV systolic or diastolic dysfunction, decrease LV mass, or reduce progression of valve stenosis.

Topics: Aged; Aortic Valve Stenosis; Blood Flow Velocity; Echocardiography, Doppler; Eplerenone; Female; Humans; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Mineralocorticoid Receptor Antagonists; Spironolactone; Statistics, Nonparametric; Ventricular Dysfunction, Left

The conventional reporting of composite endpoints in clinical trials has an inherent limitation in that it emphasizes each patient's first event, which is often the outcome of lesser clinical importance. To overcome this problem, we introduce the concept of the win ratio for reporting composite endpoints. Patients in the new treatment and control groups are formed into matched pairs based on their risk profiles. Consider a primary composite endpoint, e.g. cardiovascular (CV) death and heart failure hospitalization (HF hosp) in heart failure trials. For each matched pair, the new treatment patient is labelled a 'winner' or a 'loser' depending on who had a CV death first. If that is not known, only then they are labelled a 'winner' or 'loser' depending on who had a HF hosp first. Otherwise they are considered tied. The win ratio is the total number of winners divided by the total numbers of losers. A 95% confidence interval and P-value for the win ratio are readily obtained. If formation of matched pairs is impractical then an alternative win ratio can be obtained by comparing all possible unmatched pairs. This method is illustrated by re-analyses of the EMPHASIS-HF, PARTNER B, and CHARM trials. The win ratio is a new method for reporting composite endpoints, which is easy to use and gives appropriate priority to the more clinically important event, e.g. mortality. We encourage its use in future trial reports.

Topics: Angiotensin II Type 1 Receptor Blockers; Aortic Valve Stenosis; Benzimidazoles; Biphenyl Compounds; Cardiac Catheterization; Cardiovascular Diseases; Clinical Trials as Topic; Endpoint Determination; Eplerenone; Heart Failure; Hospitalization; Humans; Matched-Pair Analysis; Mineralocorticoid Receptor Antagonists; Proportional Hazards Models; Risk Factors; Spironolactone; Tetrazoles

Topics: Antihypertensive Agents; Aortic Valve Stenosis; Asymptomatic Diseases; Atrial Fibrillation; Eplerenone; Heart Ventricles; Humans; Hypertension; Spironolactone

Topics: Antihypertensive Agents; Aortic Valve Stenosis; Asymptomatic Diseases; Atrial Fibrillation; Eplerenone; Humans; Hypertension; Spironolactone

Topics: Aortic Valve Stenosis; Eplerenone; Humans; Mineralocorticoid Receptor Antagonists; Potassium; Spironolactone; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Topics: Aortic Valve Stenosis; Eplerenone; Humans; Mineralocorticoid Receptor Antagonists; Potassium; Spironolactone