The use of angiotensin-converting enzyme (ACE) inhibitors to treat congestive heart failure (CHF) has been shown to improve symptoms and reduce cardiovascular mortality rates. This finding has been proved in multiple studies using different drugs from this class. Despite the number of studies performed, little information exists concerning the optimal dose of ACE inhibitors in the treatment of CHF. Nanas and colleagues designed a study to observe the impact of high-dose versus standard-dose ACE inhibitors on mortality, morbidity and clinical status in patients with CHF.
Patients with moderate to severe symptoms of CHF were enrolled in the study. Subjects in group 1 took the maximal tolerable dose of enalapril (up to 20 mg per day); the enalapril doses for the subjects in group 2 were titrated up to a maximum of 60 mg per day. The enalapril dose was not increased if systolic blood pressure was less than 90 mm Hg or if the drug induced symptoms of hypotension. Patients were evaluated on a weekly basis until they reached their maximal dose and, thereafter, were followed at three, six and 12 months. In addition to the clinical assessment, patients underwent a blinded assessment of left ventricular function. Morbidity and mortality were recorded for each group.
The results from the study showed no difference in mortality or morbidity rates between the standard-dose and high-dose enalapril groups. In addition, there was no difference between the two groups in hospital admission rates for CHF exacerbations. The initiation of treatment in both groups resulted in improvements in clinical conditions within the first three months, but no further improvement occurred during the rest of the study. At the end of the study, there also was no difference between the groups in left ventricular function and New York Heart Association class.
The authors conclude that high doses of ACE inhibitors do not appear to improve survival rates in patients with CHF. A 20-mg daily dose of enalapril seems to be the optimal dose in these patients. The authors add that selected patients may benefit from higher doses of enalapril, but further trials need to be performed to determine which patients might benefit.