Long-Acting Angiotensin-Converting Enzyme Inhibitors in Congestive Heart Failure: Does Multiple-Daily Dosing Provide Additional Benefit over Once-Daily Dosing?

Objective: To determine if there is clinical evidence supporting the use of twice-daily long-acting angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure (CHF). Data Sources: Articles were identified through searches of MEDLINE and PubMed (1966–June 2005). Search terms included angiotensin-converting enzyme inhibitors, congestive heart failure, dosing, dosing schedules, captopril, enalapril, fosinopril, lisinopril, quinapril, ramipril, and trandolapril. Only articles published in English were included. Additionally, bibliographies of articles cited were used to identify additional articles. Study Selection and Data Extraction: All available articles identified by the data sources were reviewed and those deemed relevant to the review were included. Data Synthesis: Data have suggested that long-acting ACE inhibitors are more effective than short-acting ACE inhibitors for the treatment of CHF. A few ACE inhibitors approved for the treatment of CHF have twice-daily dosing schedules; these same ACE inhibitors have once-daily dosing schedules when used in the treatment of hypertension. Recent data propose greater adrenergic blockage, and, thus, decreased stimulation of the renin–angiotensin–aldosterone system, with the twice-daily dosing schedule of the long-acting ACE inhibitors. This controversy has led some providers to prescribe all long-acting ACE inhibitors twice daily in the setting of CHF, which, when unnecessary, can lead to decreased compliance, increased morbidity, and decreased quality of life. Conclusions: The available clinical studies comparing dosing schedules of long-acting ACE inhibitors have many limitations. Until a well-designed, randomized, double-blind trial of appropriate duration evaluating clinical outcomes is conducted, multiple-daily dosing schedules do not provide additional benefit over once-daily dosing schedules of long-acting ACE inhibitors in the treatment of CHF.