Angiotensin-Converting Enzyme Inhibitors, Clinical Evidence

Angiotensin-converting enzyme inhibitors affect the peripheral vascular and neurohormonal systems and have direct remodeling effects on the myocardium. Four major studies in more than 7,000 adults with heart failure have shown improved survival with the use of angiotensin-converting enzyme inhibitors [CONSENSUS: 1987] [Captopril-Digoxin: 1988] [SOLVD: 1991] [Cohn: 1991] and improved symptoms in adults with heart failure. Studies have also shown that higher doses of angiotensin-converting enzyme inhibitors are better than lower doses for improving survival and symptoms.[Packer: 1999] [van: 1998]

The role of angiotensin-converting enzyme inhibitors in the treatment of heart failure in children is much less clear. Angiotensin-converting enzyme inhibitors may have acute hemodynamic benefits in children with heart failure caused by large left-to-right shunts [Shaddy: 1988] [Montigny: 1989] [Lloyd: 1989] [Rheuban: 1990] and may also benefit children whose heart failure is caused by systemic ventricular systolic dysfunction. [Bengur: 1991] [Lewis: 1993] However, the only randomized, placebo-controlled trial of angiotensin-converting enzyme inhibitors in children with heart disease was in children with single ventricle physiology who had undergone the Fontan procedure. [Kouatli: 1997] In this study, no difference in exercise capacity between the 2 groups was found. This study was limited by the fact that these patients were not in heart failure and thus may not have been representative of children with heart failure symptoms.

At present, angiotensin-converting enzyme inhibitors are recommended for adults with left ventricular dysfunction with or without symptoms; they should be used with diuretics in patients with fluid retention and should be started at low doses and gradually increased as tolerated.


Helpful Articles

Madriago E, Silberbach M.
Heart failure in infants and children.
Pediatr Rev. 2010;31(1):4-12. PubMed abstract

Kay JD, Colan SD, Graham TP Jr.
Congestive heart failure in pediatric patients.
Am Heart J. 2001;142(5):923-8. PubMed abstract

Page Bibliography

Bengur AR, Beekman RH, Rocchini AP, Crowley DC, Schork MA, Rosenthal A.
Acute hemodynamic effects of captopril in children with a congestive or restrictive cardiomyopathy.
Circulation. 1991;83(2):523-7. PubMed abstract

CONSENSUS Trial Study Group.
Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group.
N Engl J Med. 1987;316(23):1429-35. PubMed abstract

Captopril-Digoxin Multicenter Research Group.
Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. The Captopril-Digoxin Multicenter Research Group.
JAMA. 1988;259(4):539-44. PubMed abstract

Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F, Smith R, Dunkman WB, Loeb H, Wong M.
A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.
N Engl J Med. 1991;325(5):303-10. PubMed abstract

Kouatli AA, Garcia JA, Zellers TM, Weinstein EM, Mahony L.
Enalapril does not enhance exercise capacity in patients after Fontan procedure.
Circulation. 1997;96(5):1507-12. PubMed abstract

Lewis AB, Chabot M.
The effect of treatment with angiotensin-converting enzyme inhibitors on survival of pediatric patients with dilated cardiomyopathy.
Pediatr Cardiol. 1993;14(1):9-12. PubMed abstract

Lloyd TR, Mahoney LT, Knoedel D, Marvin WJ Jr, Robillard JE, Lauer RM.
Orally administered enalapril for infants with congestive heart failure: a dose-finding study.
J Pediatr. 1989;114(4 Pt 1):650-4. PubMed abstract

Montigny M, Davignon A, Fouron JC, Biron P, Fournier A, Elie R.
Captopril in infants for congestive heart failure secondary to a large ventricular left-to-right shunt.
Am J Cardiol. 1989;63(9):631-3. PubMed abstract

Packer M, Poole-Wilson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, Rydén L, Thygesen K, Uretsky BF.
Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group.
Circulation. 1999;100(23):2312-8. PubMed abstract

Rheuban KS, Carpenter MA, Ayers CA, Gutgesell HP.
Acute hemodynamic effects of converting enzyme inhibition in infants with congestive heart failure.
J Pediatr. 1990;117(4):668-70. PubMed abstract

SOLVD Investigators.
Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators.
N Engl J Med. 1991;325(5):293-302. PubMed abstract

Shaddy RE, Teitel DF, Brett C.
Short-term hemodynamic effects of captopril in infants with congestive heart failure.
Am J Dis Child. 1988;142(1):100-5. PubMed abstract

van Veldhuisen DJ, Genth-Zotz S, Brouwer J, Boomsma F, Netzer T, Man In 'T Veld AJ, Pinto YM, Lie KI, Crijns HJ.
High- versus low-dose ACE inhibition in chronic heart failure: a double-blind, placebo-controlled study of imidapril.
J Am Coll Cardiol. 1998;32(7):1811-8. PubMed abstract