Study Suggests Drug Used for Treatment for Heart Failure in Adults May Not Be Beneficial for Children and Teens

CHICAGO, Sept. 11, 2007—Preliminary findings indicate a heart failure medication used by adults, carvedilol, may not significantly improve heart failure outcomes for children and adolescents, according to an article in the September 12 issue of JAMA.

“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 write.

Robert E. Shaddy, M.D., of Children’s Hospital of Philadelphia and the University of Pennsylvania, and colleagues evaluated the effects of the beta-blocker 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 the 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 write. “...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.”
(JAMA. 2007;298(10):1171-1179. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

EDITORIAL: THE IMPORTANCE OF RANDOMIZED CONTROLLED TRIALS IN PEDIATRIC CARDIOLOGY

In an accompanying editorial, Samuel S. Gidding, M.D., of Nemours Cardiac Center, Wilmington, Del., comments 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.”
(JAMA. 2007;298(10):1214-1216. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Please see the article for additional information, including other affiliations, financial disclosures, funding and support, etc.

For More Information: Contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or email: mediarelations@jama-archives.org .

Posted: September 2007

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