Abstract 265: Morning Dosing of Eplerenone Improves Daytime Blood Pressure Control but Not Fibrinolytic Balance

Abstract

The renin angiotensin-aldosterone system has a diurnal variation, proceeding morning increases in blood pressure and plasminogen activator inhibitor-1 (PAI-1) levels. The RAAS is particularly active in individuals with metabolic syndrome (MetS) resulting in increased blood pressure and elevated PAI-1 levels. Eplerenone is a mineralocorticoid antagonist that is approved for the treatment of hypertension with a half-life of 4-6 hours but can be prescribed once or twice daily. This is a double-blind crossover study that examines the effects of morning (AM) vs. nighttime (PM) administration of eplerenone on blood pressure, PAI-1, plasma renin activity (PRA), and plasma aldosterone levels. Twenty subjects with MetS were studied on three 24-hour inpatient study days on hydrochlorothiazide (25mg) alone and with concomitant morning or evening dosing of eplerenone (100mg). Vital signes were taken and blood was drawn every three hours. There was a statistically significant increase in aldosterone levels with both AM (266±21 ng/dL) and PM (320±31 ng/dL) dosing of eplerenone compared to baseline (194±11 ng/dL) (both p < 0.001) with no significant difference between the two dosing strategies. There was a trend suggesting a daytime (8AM-5PM) systolic blood pressure reduction of 4.9±1.4 mmHg (p = 0.06) with AM dosing. Furthermore, diastolic blood pressure appeared less volatile with AM dosing (range = 38 mmHg vs. 47 mmHg for baseline and PM). There was no difference between baseline, AM and PM dosing with regard to PRA, PAI-1, serum potassium or creatinine. These findings suggest that there may be improved overall control of blood pressure with AM dosing of eplerenone, without obvious deleterious effects such as elevated creatinine or potassium levels. Furthermore, increases in aldosterone did not result in increases in PAI-1. Consequently rational dosing strategies such as this merit further investigation.