Effect of angiotensin-converting enzyme inhibitors on ventricular remodeling and survival following myocardial infarction.

Abstract

OBJECTIVE:

To discuss the effects of angiotensin-converting enzyme (ACE) inhibitors on ventricular remodeling and survival after acute myocardial infarction (AMI). An overview is provided of the pathophysiologic changes produced by AMI and the ventricular remodeling process. ACE inhibitors have been studied for their use in the prevention of ventricular remodeling and reduction in postinfarction mortality. Trials in humans and animals are reviewed, including study methods, results, and limitations.

DATA SOURCES:

MEDLINE searches identified applicable literature, including experimental trials and review articles.

STUDY SELECTION:

All clinical trials of ACE inhibitors following AMI were reviewed.

DATA EXTRACTION:

Morbidity and mortality data evaluating the effect of postinfarction ventricular remodeling are rare. At the time of publication, all available clinical trials studying the effects of ACE inhibitors on postinfarction ventricular remodeling were included, regardless of whether morbidity and mortality were assessed. Data from the Survival and Ventricular Enlargement (SAVE) and Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II) trials include almost 10,000 patients. Data were extracted by two independent observers. Data quality and validity were assessed based on sample size, stratification of study population, and statistical power of the studies.

DATA SYNTHESIS:

ACE inhibitors may prevent the deleterious consequences of AMI, including ventricular remodeling and neurohumoral activation. Ventricular hypertrophy begins acutely following infarction, an early physiologic response to myocardial injury. Hemodynamic benefits from the initial phase of left ventricular hypertrophy include increased ventricular working capacity, normalized systolic wall stress, and maintenance of stroke volume. Although acute dilatation may delay hemodynamic deterioration for six to eight months, it also results in reduced coronary reserve, decreased ventricular compliance, and altered myocardial contractility. With chronic dilatation, the beneficial effects reach a plateau, stroke volume decreases, contractility is reduced, and cardiac failure may ensue. Ventricular hypertrophy is associated with worsened prognosis following infarction and may be the most important single determinant of late prognosis. Ventricular hypertrophy contributes to postinfarction heart failure, angina, and sudden death. Clinical trials show a beneficial effect of the ACE inhibitor captopril on the prevention of left ventricular dysfunction. Although captopril therapy significantly improved survival and myocardial function following AMI in the SAVE trial, these results cannot be generalized to all patient subpopulations. The CONSENSUS II trial demonstrated a decreased survival rate when enalapril was administered within 24 hours of AMI, indicating that timing of therapy may be an important consideration. Captopril therapy may positively affect outcome when initiated 3-16 days following infarction in patients with ejection fractions below 40 percent and who have no signs of ischemia or heart failure. Based on the CONSENSUS II results, enalapril therapy immediately following AMI cannot be recommended.

CONCLUSIONS:

Clinical trials have demonstrated that ACE inhibitors can limit ventricular hypertrophy following AMI, resulting in clinical benefit and improved survival. These effects may be secondary to modulation of neurohumoral activation or the antiischemic effect of ACE inhibitors, which may also reduce the incidence of reinfarction. Early intervention with ACE inhibitors (within 3-16 days of infarction) can slow the progression of cardiovascular disease and improve the survival rate.

• Authors: C Beckwith, M A Munger
• Journal: The Annals of pharmacotherapy (Ann Pharmacother) Vol. 27 Issue 6 Pg. 755-66 (Jun 1993) ISSN: 1060-0280 [Print] United States
• PMID: 8329800 (Publication Type: Journal Article, Review)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
• Animals
• Clinical Trials as Topic
• Heart Ventricles (drug effects, physiopathology)
• Humans
• Hypertrophy, Left Ventricular (etiology, prevention & control)
• Hypertrophy, Right Ventricular (etiology, prevention & control)
• Myocardial Infarction (drug therapy, mortality)
• Prognosis