Evolving rationale for angiotensin-converting enzyme inhibition in chronic heart failure.
The rationale behind the use of angiotensin-converting enzyme (ACE) inhibitors has evolved considerably since their approval for the treatment of hypertension. The initial rationale behind their use for the treatment of chronic heart failure was to duplicate with one agent the hemodynamic effects produced by the hydralazine-isosorbide dinitrate combination, i.e., increasing cardiac output while reducing ventricular filling pressures. The observation that the acute hemodynamic effects of ACE inhibitors did not predict long-term clinical benefits led to the search for mechanisms other than hemodynamic improvement. Attenuation or even reversal of left ventricular dilatation after myocardial infarction, which was first reported with ACE inhibition in an experimental model of myocardial infarction and subsequently in patients with recent myocardial infarction, provided a new rationale for the use of these inhibitors for chronic heart failure. However, this apparent prevention of left ventricular dilatation by ACE inhibitors is less apparent in patients with congestive heart failure due to left ventricular systolic dysfunction (decreased ejection fraction) than in patients with recent myocardial infarction. Furthermore, the unexpected finding that long-term ACE inhibition decreases the incidence of recurrent myocardial infarction in patients with coronary artery disease and an already reduced systolic function, suggested the hypothesis that vascular protection may provide most of the clinical benefits of ACE inhibitors. This hypothesis was successfully tested by demonstrating a lower incidence of cardiovascular events in high-risk vascular patients randomized to long-term ACE inhibition with ramipril. Accordingly, the current rationale behind the use of ACE inhibitors in patients with chronic heart failure is largely that of vascular protection.
Banerjee
Anita
A
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Talreja
Ashok
A
Sonnenblick
Edmund H
EH
LeJemtel
Thierry H
TH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002908:Chronic Disease; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans
D000806:Angiotensin-Converting Enzyme Inhibitors