Twice-Daily Administration of a Long-Acting Angiotensin-Converting Enzyme Inhibitor Has Greater Effects on Neurohumoral Factors than a Once-Daily Regimen in Patients with Chronic Congestive Heart Failure

Although many clinical trials have evaluated the use of long-acting angiotensin-converting enzyme (ACE) inhibitors in patients with chronic congestive heart failure (CHF), there are no data regarding whether a once-daily or twice-daily regimen is preferable with respect to effects on the neuroendocrine system. To address this issue, the authors evaluated the comparative effects of the administration schedule on neurohumoral factors and autonomic nervous activity in patients with CHF. Thirty-two patients with mild compensated CHF received lisinopril (5-20 mg/d) orally either once a day (n = 17) or twice a day (n = 15) for more than 3 months. After this initial therapy, patients receiving a once-daily regimen switched to a twice-daily regimen and vice-versa, and patients were followed for an additional 3 months. Neurohumoral factors and the coefficient of variance in the electrocardiographic R-R interval (CVRR) were measured. Hemodynamic parameters, renal function, plasma concentrations of brain natriuretic peptide and aldosterone, and CVRR did not differ between the two regimens. However, the plasma concentration of norepinephrine was significantly lower, and plasma renin activity tended to be lower with the twice-daily regimen. These findings suggest that twice-daily administration of long-acting ACE inhibitors may have better effects on the neuroendocrine system than a once-daily regimen in patients with mild CHF.