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REVIEW ARTICLES

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

^a Baker Medical Research Institute, Melbourne, 8008, Australia

Manuscript received August 12, 1998; revised manuscript received November 23, 1998, accepted January 5, 1999.

Reprint requests and correspondence: Dr. Hans Peter Brunner-La Rocca, Baker Medical Research Institute, PO Box 6492, Melbourne 8008, Victoria, Australia

One possible intervention to interrupt the deleterious effects of the renin-angiotensin system is suppression of angiotensin II (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 1 (AT1) receptors are believed to promote the known deleterious effects of Ang II. Therefore, AT1 receptor antagonists have been recently introduced into therapy for hypertension and congestive heart failure (CHF). Although there are significant differences between the effects of AT1 receptor antagonists and ACE inhibitors including the unopposed stimulation of angiotensin II type 2 (AT2) receptors by AT1 receptor antagonists, the discussion of whether ACE inhibitors, AT1 receptor antagonists or the combination of both are superior in the pharmacotherapy of CHF is still largely theoretical. Accordingly, AT1 receptor antagonists are still investigational. Angiotensin-converting enzyme inhibitors remain first line therapy in patients with CHF due to systolic dysfunction. However, in patients not able to tolerate ACE inhibitor induced side effects, in particular cough, AT1 receptor antagonism is a good alternative. In clinical practice, emphasis should be placed on increasing the utilization of ACE inhibitors, as more than 50% of patients with CHF do not receive ACE inhibitors. In addition, the majority of those on ACE inhibitors receive doses lower than the dosage used in the large clinical trials. Although not yet completely proved, it is likely that high doses of ACE inhibition are superior to low doses with respect to prognosis and symptoms.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   Ang = angiotensin   AT1 = angiotensin II type 1   AT2 = angiotensin II type 2   B1 = bradykinin type 1   B2 = bradykinin type 2   CHF = congestive heart failure   MCP-1 = monocyte chemoattractant protein-1   PAI-1 = plasminogen activator inhibitor C-1   RAS = renin angiotensin system   t-PA = tissue plasminogen activator

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