Therapeutic implications of escape from angiotensin-converting enzyme inhibition in patients with chronic heart failure.
The level of inhibition of the angiotensin-converting enzyme (ACE) provided by standard doses of ACE inhibitors may only be partial during long-term treatment in patients with severe chronic heart failure (CHF). Partial ACE inhibition with time is often referred to as escape from ACE inhibition and labeled ACE escape. Several lines of evidence suggest that ACE escape occurs in patients with severe CHF. Plasma levels of angiotensin II rise above initial values during long-term ACE inhibition, and the effects of ACE inhibitors on cardiac remodeling and lowering of sympathetic nervous system activity attenuate after 1 year of treatment. Moreover, angiotensin II type I receptor blockade (ARB) produces clinical and hemodynamic benefits in patients with CHF who are already receiving ACE inhibitors. The therapeutic implications of ACE escape include evaluation of higher- than-standard doses of ACE inhibitors and routine addition of ARB to ACE inhibition in patients with severe CHF. Data are reviewed to demonstrate that ACE escape reflects inadequate ACE dosage rather than a decrease in ACE inhibition occurring with time.
Ennezat
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Albert Einstein College of Medicine, Division of Cardiology, Forchheimer Building, Room G 46,1300 Morris Park Avenue, Bronx, NY 10461, USA.
Berlowitz
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M
Sonnenblick
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EH
Le Jemtel
T H
TH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013777:Tetrazoles / Q000627:therapeutic use; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D004656:Enalapril; C081643:candesartan