Heart Failure Drug Fails in Trial
But a second medication appears more promising
WEDNESDAY, March 27, 2002 (HealthDayNews) -- A drug that relaxes blood vessels doesn't appear to help people with flare-ups of chronic heart failure and may even worsen the problem, a new study has found.
The study, appearing in today's issue of the Journal of the American Medical Association, showed that heart patients were better off without the drug, called milrinone, which increased the risk of seriously low blood pressure and abnormal heartbeats.
"Milrinone isn't working," said Dr. Mihai Gheorghiade, a Northwestern University cardiologist who led the study.
Dr. Philip Poole-Wilson, a cardiologist at Imperial College in London and author of an editorial accompanying the journal articles, said milrinone "has probably been used too much and the indications for its use are getting very much more narrow." An earlier study showed that the drug was not effective -- and potentially dangerous -- for people with chronic heart failure.
However, Poole-Wilson said, the drug may be appropriate for people with other forms of congestive heart failure. Who these patients are isn't yet known, he added, because of the paucity of good clinical evidence for treatments of this disease.
A second study, also appearing the journal, found that a newer medication markedly improved blood flow in a similar group of patients.
Experts said the two studies are important because they represent the first large-scale, placebo-controlled trials of drugs to treat worsening heart failure.
Almost 5 million Americans suffer from heart failure, and 200,000 a year die from the disease, which involves a fluid build-up in the lungs that forces patients to strain for breath. Fluid can also pool in the legs. Heart failure can lead to liver congestion, abnormal heart rhythms, and, ultimately, death.
Beta-blockers, ACE inhibitors and a variety of other drugs can improve heart function in patients with chronically weak pumps. But doctors have hit on nothing so far that prolongs life in those hospitalized with acute failure.
The problem, heart experts said, is that patients, their families and their physicians are frustrated by the lack of a successful remedy for severe exacerbations of heart failure. Everyone wants to do something, but nothing seems to work. So drugs that might ordinarily be avoided are tried, in the hope that patients might have a glimmer of improvement.
In the first study, a team led Gheorghiade compared intravenous milrinone with placebo therapy in 949 men and women hospitalized with worsening congestive heart failure (CHF). The patients' average age was 65. "This basically reflects how patients admitted with CHF look. It's not a unique population," Gheorghiade said.
Despite being approved to treat heart failure, milrinone -- sold as Primacor by Sanofi-Synthelabo Inc., which funded the trial -- appeared to be a lesser option than sugar water in the study.
Patients receiving infusions of the drug had three times as many bouts of seriously low blood pressure (10.7 percent vs. 3.2 percent) and were three times as like to develop new arrhythmias (4.6 percent vs. 1.5 percent) as patients who got the placebo.
Both groups spent about the same number of days in the hospital over the next 60 days (six times vs. seven times) and had roughly the same rates of death.
"Although we're using medications, their use is empiric, and many times we don't know what we're doing," said Gheorghiade, associate chief of cardiology at Northwestern's Feinberg School of Medicine in Chicago.
Gheorghiade said milrinone might be better for people with more severe heart failure. Its failure in this trial "doesn't mean doctors shouldn't use it, but they should make sure that other therapies are not working first."
In the second paper, researchers found that IV infusions of the drug nesiritide were better than dummy treatment and nitroglycerin at improving blood flow and pressure readings in people hospitalized for worsening congestive heart failure.
Patients on nesiritide, a synthetic hormone secreted by the heart that's sold as Natrecor by Scios Inc., also reported less dyspnea (shortness of breath) three hours after treatment than those on placebo, though not compared with those taking nitroglycerin. In a 24-hour comparison between the two drugs, Natrecor was better than nitroglycerin at improving blood flow, but not at easing breathing or bettering overall clinical status.
Dr. James Young, medical director of the Kaufman Center for Heart Failure at the Cleveland Clinic Foundation and a co-author of the study, said the findings support using Natrecor. "You much more rapidly get patients feeling better," and, with the help of a diuretic, get them dried out, said Young. "These changes and these differences are clinically significant."
The Food and Drug Administration approved Natrecor in 2001, making it the first new IV drug for heart failure in more than a decade. Young said the drug is now being widely prescribed.
But he added, neither study followed heart failure patients for very long, and there's no evidence that either Natrecor or Primacor can help reduce deaths from the disease.
"We have no idea what either of these drugs do to survival," he said.
Roughly half the people who develop advanced heart failure die within a year.
What's needed in addition to more trials, Gheorghiade said, are clinical guidelines like those in place for treating heart attacks and chest pain.
Officials at Sanofi-Synthelabo could not be reached for comment.