A remarkable medical story: benefits of angiotensin-converting enzyme inhibitors in cardiac patients

Abstract

The development of angiotensin-converting enzyme inhibitors (ACE inhibitors) has been one of the most remarkable stories in the treatment of cardiovascular diseases. Angiotensin converting enzyme inhibitors have several acute and sustained hemodynamic effects that are beneficial in the presence of left ventricular (LV) dysfunction. They increase cardiac output and stroke volume and reduce systemic vascular resistance as well as pulmonary capillary wedge pressure. The hemodynamic benefits are associated with improvement in the signs and symptoms of congestive heart failure (CHF) as well as decreased mortality, regardless of the severity of CHF. In patients with asymptomatic LV dysfunction, therapy with ACE inhibitors prevented the development of CHF and reduced hospitalization and cardiovascular death. They also increase survival when administered early after an acute myocardial infarction (MI). Most recently, ACE inhibition was associated with improved clinical outcomes in a broad spectrum of high-risk patients with preserved LV function. The mechanism of ACE inhibitors benefits is multifactorial and includes prevention of progressive LV remodeling, prevention of sudden death and arrhythmogenicity and structural stability of the atherosclerotic process. Evidence suggests that ACE inhibitors are underutilized in patients with cardiovascular diseases. Efforts should be directed to prescribe ACE inhibitors to appropriate patients in target doses. It is reasonable to believe that ACE inhibitors have a class effect in the management of LV dysfunction with or without CHF and acute MI. Whether the same is true for ACE inhibitors in the prevention of ischemic events is not known yet.

Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association

“…217,218 As such, ACEIs are considered a cornerstone of treatment for HF with reduced EF in adults, with benefits in all New York Heart Association functional classifications.…”

“…Of course, for any patient with NMD and dilated cardiomyopathy, ACEI or ARB treatment is recommended on the basis of clinical trials showing benefits in the absence of NMD. 217,218 Use of an ACEI carries risks of angioedema, chronic cough, and other side effects that are attributable to the mechanism of action of this category of medications. Selective pharmacological blockade of the angiotensin receptor was developed to bypass this mechanism of action while still achieving favorable neurohormonal antagonism.…”

Navigating the Crossroads of Coronary Artery Disease and Heart Failure

“…71,72 Several studies have shown that ACE inhibition reduces the incidence of HF and mortality after an acute MI, possibly by preventing LV remodeling, reinfarction, and sudden death. 73 In the SAVE trial, which enrolled patients with LVEF Ͻ40% and no symptoms and signs of HF, captopriltreated patients had a significantly reduced incidence of mortality and experienced a 22% reduction in the risk of hospitalization for HF and 25% of recurrent MI. 33 The Acute Infarction Ramipril Efficacy (AIRE) trial differed from SAVE in that the patients had overt signs of HF after an acute MI and a measure of LVEF was not obtained in all patients.…”

A possible role for hydrochlorothiazide (HCTZ) as "enhancer" of zofenopril activity at the tissue level

“…Angiotensin II has been shown to have a deleterious effect at different levels including the cardiac, vascular and renal tissues [4]. Pharmacological agents such as ACE inhibitors, that actively prevent the formation of angiotensin II, may therefore have favourable effects in terms of end-organ protewction, beyond their activity on blood pressure (BP) [5].…”