Study of carvedilol in a pediatric population suggests it may not significantly improve outcomes for children and adolescents with heart failure
Preliminary findings on use of carvedilol in a pediatric
population suggest that it may not significantly improve outcomes for children
and adolescents with heart failure, according to an article in the September 12
issue of the Journal of the American Medical Association.
“Heart failure due to systemic ventricular dysfunction
is a significant medical problem for children and represents the reason for at
least 50 percent of pediatric referrals for heart transplantation. To date, there
have been no large randomized controlled trials of any medication in children
and adolescents with chronic heart failure. Treatment recommendations in children
and adolescents with heart failure are extrapolated from the results of clinical
trials conducted in adults, which may be problematic,” the authors wrote.
Robert E. Shaddy, MD, of Children’s Hospital of Philadelphia
and the University of Pennsylvania, and colleagues evaluated the effects of carvedilol
in 161 children and adolescents with heart failure. In addition to treatment with
conventional heart failure medications, patients were randomized to receive placebo
or carvedilol for eight months. The size of the dosage was determined by the weight
of the child.
The researchers found no statistically significant difference
between treatment groups with regard to the percentage of patients who improved,
worsened, or were unchanged during the course of the study. Among 54 patients
assigned to placebo, 56 percent improved, 30 percent worsened and 15 percent were
unchanged. Among 103 patients assigned to carvedilol, 56 improved, 24 percent
worsened and 19 percent were unchanged.
“This study did not detect a treatment effect of carvedilol
on the primary composite end point of clinical heart failure outcomes. It is possible
that children and adolescents with heart failure do not receive benefit from carvedilol;
this would represent the first heart failure population not to show benefit with
beta-blockade and is inconsistent with the many small studies supporting the benefit
of beta-blockade in this patient population to date. It is unclear why carvedilol
would be beneficial in adults with heart failure but not in children and adolescents,”
the authors wrote. “… given the lower than expected event rates, the trial may
have been underpowered. There may be a differential effect of carvedilol in children
and adolescents based on ventricular morphology.”
In an accompanying editorial, Samuel S. Gidding, MD,
of Nemours Cardiac Center, Wilmington, Del., commented on the findings of Shaddy
and colleagues.
“A subtle but important difference between pediatric
and adult research relates to goals. Adult cardiac trials, whether related to
heart failure or prevention of recurrent myocardial infarction, are considered
successful when the inevitable is delayed. For most adults, the inevitable still
occurs. For children with heart disease, the goals are different: to treat pediatric
patients effectively so that they can experience decades of as normal a quality
of life as possible. This difference provides the ethical rationale for independent
pediatric clinical research and rigorous clinical trials in pediatric patients
as opposed to a reliance on adult outcomes, which often are not generalizable
to children. After all, and especially in pediatric cardiology research and treatment,
children are not simply little adults.”
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