Recent insight into therapy of congestive heart failure: Focus on ACE inhibition and angiotensin-II antagonism

One possible intervention to interrupt the deleterious effects of the renin -angiotensin system is suppression of angiotensin LI (Ang II) formation by inhibition of angiotensin-converting enzyme (ACE). However, ACE inhibition incompletely suppresses Ang II formation and also leads to accumulation of bradykinin. Angiotensin II type I (AT1) receptors are believed to promote t he known deleterious effects of Ang II. Therefore, ATI receptor antagonists have been recently introduced into therapy for hypertension and congestive heart failure (CHF). Although there are significant differences between th e effects of AT1 receptor antagonists and ACE inhibitors including the unop posed stimulation of angiotensin II type 2 (AT2) receptors by AT1 receptor antagonists, the discussion of whether ACE inhibitors, AT1 receptor antagon ists or the combination of both are superior in the pharmacotherapy of CHF is still largely theoretical. Accordingly AT1 receptor antagonists are stil l investigational. largely first line therapy in patients with CHF due Angi otensin-converting enzyme inhibitors remain to systolic dysfunction. Howeve r, in patients not able to tolerate ACE inhibitor induced side effects, in particular cough, AT1 receptor antagonism is a good alternative. In clinica l practice, emphasis should be placed on increasing the utilization of ACE inhibitors, as more than 50% of patients with CHF do not receive ACE inhibi tors. In addition, the majority of those on ACE inhibitors receive doses lo wer than the dosage used in the large clinical trials. Although not yet com pletely proved, it is likely that high doses of ACE inhibition are superior to low doses with respect to prognosis and symptoms. (C) 1999 by the Ameri can College of Cardiology.