Heart Failure Drug Not Effective
DURHAM, N.C. --More than 5 million people in the U.S. are affected with chronic heart failure (CHF), a condition that results in approximately 1 million hospitalizations annually. Hospitalization usually is associated with a poor prognosis, high hospital readmission rates and death within 30 to 60 days after discharge.
In this patient population, placebo-control, randomized clinical studies, the "gold standard of medicine" from which evidence-based management guidelines normally are derived, are lacking, says heart failure expert Mihai Gheorghiade, M.D., professor of medicine and vice-chief of cardiology at The Feinberg School of Medicine and Northwestern Memorial Hospital.
By contrast, there are many placebo-controlled, randomized clinical studies for other conditions that normally result in hospitalization, namely, acute myocardial infarction (MI), or heart attack.
"When compared to MI, CHF is just as devastating for patients, but there hasn't been nearly the number of large clinical trials," said Duke University Medical Center cardiologist Michael Cuffe, M.D. "The problem is that these trials are very difficult to conduct, and that?s what makes this study so important."
Gheorghiade and Cuffe, with co-researchers from Duke and other medical centers, conducted the first large placebo-controlled, randomized trials of existing therapies for exacerbation of chronic CHF in order to help develop treatment guidelines for this condition.
Results of one of these studies, on the use of milrinone, an intravenous drug administered to increase heart muscle contractility and approved by the FDA to treat worsening CHF, were published in the March 27 issue of the Journal of the American Medical Association.
Results of the other studies, which are investigating the use of beta-blockers, new diuretics or other drugs, are forthcoming from the same group of researchers.
In the current study, 950 patients from 78 medical institutions participated in the so-called OPTIME-CHF, for Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure.
The study evaluated whether the short-term use of milrinone in addition to standard therapy could improve outcomes, i.e., shorten hospitalizations, improved symptoms or improve dosing of life-saving therapies.
The researchers found that the routine addition of IV milrinone, a relatively common intervention for these patients, did not improve outcome, but, rather, was associated with increased early treatment failure, particularly due to new atrial arrhythmias and significant lowering of blood pressure.
The results of the OPTIME-CHF study therefore do not support the routine use of milrinone for patients hospitalized for worsening heart failure, and they point out the importance of evaluating existing therapies or new therapies with placebo-controlled, randomized trial protocols for patients hospitalized with worsening heart failure.
"Milrinone is labeled for use in patients hospitalized with an exacerbation of their CHF. What is significant is that we found over the intermediate term that milrinone not only didn?t appear to help these patients, but also was associated with additional problems," Cuffe said.
"The difference between this study and the studies that led to milnirone's approval was that we looked at how the patients actually fared over the longer term, beyond its short-term effects on hemodynamics," he said.
Other researchers on OPTIME-CHF were Dr. Robert Califf and Dr. Christopher O'Connor, from Duke; Dr. Kirkwood F. Adams, Jr., University of North Carolina at Chapel Hill; Dr. Barry M. Massie, VAMC, San Francisco; Dr. Ileana Pina, University Hospital of Cleveland, Ohio; Dr. Rebecca Quigg, The Feinberg School of Medicine, Chicago; and Dr. Marc A. Silver, Christ Hospital and Medical Center, Oak Lawn, Ill.
This investigator-initiated study was sponsored by Sanofi-Synthelabo, Inc., New York, N.Y. All authors served as consultants and/or received grants from Sanofi-Synthelabo.