Drug Strongly Reduces Risk of Heart Failure in Children After Cardiac Surgery; Clinical Trial Was Largest Ever Following Heart Surgery in Children

02/27/2003

PHILADELPHIA, Feb. 27 /PRNewswire/ -- Infants and young children with heart defects benefited from a drug they received shortly after cardiac surgery. The drug, milrinone, significantly reduced the risk of low cardiac output syndrome (LCOS), a life-threatening reduction in the heart's pumping ability.

The study, involving 238 patients at 31 hospitals in the United States and Canada, was the largest randomized trial in children following heart surgery. Researchers from the Cardiac Center at The Children's Hospital of Philadelphia led the study, which appears in the Feb. 25 issue of Circulation, the official journal of the American Heart Association.

Nearly one of every 100 children is born with a heart defect, of which more than one-third will require surgery. The children in this study all had heart conditions that required corrective open-heart surgery under cardiopulmonary bypass, usually within their first year of life.

The patients were randomly divided into three groups: one receiving a low dose of milrinone, one receiving a high dose, and a group that received a placebo. During the critical first 36 hours after surgery, the high-dose group was 55 percent less likely to suffer LCOS compared to the placebo group. "This provides hard evidence for using this drug in children," said co-principal investigator Gil Wernovsky, M.D., medical director of the Cardiac Intensive Care Unit at Children's Hospital.

Milrinone improves the heart's ability to squeeze and relax, as well as lowering blood pressure in blood vessels. It has been used to treat adults with acute heart failure, and has previously been used to treat children after they had developed LCOS following heart surgery. The current study, called PRIMACORP for prophylactic intravenous use of milrinone after cardiac operation in pediatrics, was the first to investigate use of the drug before LCOS symptoms developed.

"This trial was a genuine partnership between industry and academic medicine," said Dr. Wernovsky. Sanofi-Synthelabo Inc., which manufactures milrinone, sponsored the study at 31 medical centers. "It was particularly important that milrinone's side effects and efficacy were fully tested in children in a large, placebo-controlled trial. Many drugs used for children have never been thoroughly tested in children, and we can't assume that children are just small adults." He added that data from this trial can be further analyzed for pharmacokinetics - how children's bodies process the drug - which may be different from the results in adults.

Side effects of milrinone that have been reported in adults, such as low blood pressure, blood platelet abnormalities, and irregular heart rhythms, occurred infrequently in the children studied, and were not more common in patients receiving milrinone compared to those who received a placebo.

"Although this trial did not directly study other benefits such as shorter hospitalizations and fewer postoperative complications, we believe that these benefits may result from reducing low cardiac output," said co-principal investigator Timothy M. Hoffman, M.D. "Those questions need to be pursued in future research."

Drs. Wernovsky and Hoffman submitted the study from the Cardiac Center at The Children's Hospital of Philadelphia, as did a third co-author, Thomas L. Spray, M.D., chief of the Division of Cardiothoracic Surgery. (Dr. Hoffman is currently at Ohio State University.) The Cardiac Center is a comprehensive center for the care of infants, children and young adults with congenital and acquired heart disease. Other co-authors represented pediatric cardiology programs at six other hospitals.

Founded in 1855 as the nation's first pediatric hospital, The Children's Hospital of Philadelphia is ranked today as he best pediatric hospital in the nation by a comprehensive Child magazine survey. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 381- bed hospital recognition as a leading advocate for children and adolescents from before birth through age 19. For more information, visit http://www.chop.edu.

CONTACT: John Ascenzi of The Children's Hospital of Philadelphia, 215-590-7332 or Ascenzi@email.chop.edu.