Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines.
OBJECTIVE
To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer.


METHODS
This was a randomized, double-blind, controlled clinical trial comparing enalapril to placebo in 135 long-term survivors of pediatric cancer who had at least one cardiac abnormality identified at any time after anthracycline exposure.


RESULTS
There was no difference in the rate of change in MCI per year between enalapril and placebo groups (0.30 v 0.18 L/min/m(2); P =.55). However, during the first year of treatment, the rate of change in LVESWS was greater in the enalapril group than in the placebo group (-8.59 v 1.85 g/cm(2); P =.033) and this difference was maintained over the study period, resulting in a 9% reduction in estimated LVESWS by year 5 in the enalapril group. Six of seven patients removed from random assignment to treatment because of cardiac deterioration were initially treated with placebo (P =.11), and one has died as a result of heart failure. Side effects from enalapril included dizziness or hypotension (22% v 3% in the placebo group; P =.0003) and fatigue (10% v 0%; P =.013).


CONCLUSIONS
Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year; this reduction was maintained over the study period. Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions.
Center for Outcomes Research, Children's Hospital of Philadelphia, 3535 Market St, Suite 1029, Philadelphia, PA 19104, USA. Silber@email.chop.edu
Jeffrey H
JH
Silber
Avital
A
Cnaan
Bernard J
BJ
Clark
Stephen M
SM
Paridon
Alvin J
AJ
Chin
Jack
J
Rychik
Alexa N
AN
Hogarty
Mitchell I
MI
Cohen
Gerald
G
Barber
Monika
M
Rutkowski
Thomas R
TR
Kimball
Cynthia
C
Delaat
Laurel J
LJ
Steinherz
Huaqing
H
Zhao
D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000627:therapeutic use / Q000633:toxicity*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004311:Double-Blind Method; D004656:Enalapril / Q000008:administration & dosage*; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D006334:Heart Function Tests / Q000187:drug effects; D006801:Humans; D016014:Linear Models; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D017741:Survivors; D016896:Treatment Outcome
D018943:Anthracyclines; D004656:Enalapril