Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of heart failure caused by left ventricular systolic dysfunction

• Published in: Progress in cardiovascular diseases Vol. 41; no. 4; pp. 265 - 300
• Main Authors: Sander, Gary E, McKinnie, James J, Greenberg, Stanley S, Giles, Thomas D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.1999
• Subjects: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Blood Vessels - metabolism; Heart Failure - drug therapy; Heart Failure - etiology; Heart Failure - metabolism; Humans; Myocardium - metabolism; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin - metabolism; Treatment Outcome; Ventricular Dysfunction, Left - complications; Ventricular Dysfunction, Left - metabolism; Ventricular Dysfunction, Left - physiopathology
• ISSN: 0033-0620; 1532-8643
• DOI: 10.1053/pcad.1999.0410265

Activation of the renin-angiotensin-aldosterone system (RAAS) in left ventricular systolic dysfunction is a critically important determinant in the pathophysiologic processes that lead to progression of heart failure and sudden death. Angiotensin II, acting at the specific angiotensin receptor (AT 1-R), activates a series of intracellular signaling sequences which are ultimately expressed within the cardiovascular system as vasoconstriction and associated vascular hypertrophy and remodeling. Angiotensin converting enzyme (ACE) inhibition leads to increases in the vasodilatory peptides bradykinin and substance P and at least an initial reduction in angiotensin II concentrations. AT 1-R blocking drugs prevent access of angiotensin II to the AT 1-R and thus prevent cellular activation. ACE inhibitors have clearly been demonstrated through a large number of clinical trials to increase survival in congestive heart failure, primarily by reducing the rate of progression of left ventricular dilatation and decompensation. However, this beneficial effect diminishes over time. Preliminary short-term clinical studies evaluating the efficacy of AT 1-R blocking drugs in the treatment of heart failure have suggested that they elicit similar hemodynamic and neuroendocrine effects as do the ACE inhibitors. The combination ACE inhibitors and AT 1-R blocking drugs offer the theoretical advantage of increasing bradykinin while blocking the actions of angiotensin II, and thus possibly show a synergistic effect. Again, preliminary studies have yielded encouraging results that are difficult to interpret because neither ACE inhibitor nor the AT 1-R blocking drug doses were titrated to tolerance. Pharmacological manipulation of the RAAS has led to better understanding of its role in heart failure and improved clinical outcomes. Copyright © 1999 by W.B. Saunders Company Progress in Cardiovascular Diseases, Vol. 41, No. 4 (January/February), 1999: pp 265-300