April 25, 1997

NIH study halted early due to defibrillator’s effectiveness

NIH study halted early due to defibrillator's effectiveness

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Dr. Mark Wathen talks with patient Danny Moffit about a new, highly effective, implantable defibrillator.

An implantable defibrillator has proven so much more effective than medication in reducing deaths from life-threatening heart arrhythmias that the National Institutes of Health has called an early halt to a study comparing the two.

The landmark trial was conducted at Vanderbilt University Medical Center and 49 other centers in the United States. VUMC was the only participating center in Tennessee.

The study found a nearly 25 percent reduction in deaths among patients with the implantable cardiac defibrillators (ICDs) compared with those who had been treated with medication, according to an NIH news release announcing the results.

If the results were applied to the total population at risk, more than 1,000 lives could be saved each year in the United States, the news release stated.

"We have called all the patients that we enrolled in the study and their referring physicians to tell them the results of the trial," said Dr. Mark S. Wathen, assistant professor of Medicine, the principal investigator in the trial at VUMC.

"We have already implanted an ICD in one patient who had been randomized to drug therapy in the trial. We have learned what the best medicine is, and we're practicing it."

Co-investigators at VUMC were Dr. Dan M. Roden, professor of Medicine and Pharmacology; Dr. Katherine T. Murray, assistant professor of Medicine and Pharmacology; Dr. John T. Lee, associate professor of Medicine; Dr. Mark E. Anderson, assistant professor of Medicine; and Dr. Jeffrey Rottman, associate professor of Medicine. The nursing coordinator was Nancy Conners.

The Antiarrhythmics vs. Defibrillators (AVID) Trial enrolled patients with a history of life-threatening abnormal heart rhythm involving the ventricles, the pumping chambers of the heart.

Half the participants had a dangerously chaotic rhythm called ventricular fibrillation (VF), while the other half had a serious ventricular tachycardia (VT) – a too-fast heart beat originating from rapid electrical impulses in the ventricles.

Of the estimated 350,000 sudden cardiac deaths that occur in the United States each year, most are believed to be due to these two conditions. Heart attack and cardiomyopathy (heart muscle disease) are common causes of VF and VT.

In the AVID trial, patients were randomly assigned to be treated with either antiarrhythmic drugs or with an ICD.

An ICD recognizes dangerous arrhythmias and works to restore a normal rhythm by pacing the heart or delivering an electric shock. It is implanted beneath the skin in the chest and is attached to the heart with leads.

After one year, patients in the ICD group experienced a nearly 38 percent reduction in deaths compared to the group of patients who were treated with medication. In the second and third years, the ICD group had about a 25 percent reduction in deaths.

"Even though the relative benefit for the implantable defibrillators compared to drugs declined over time, the difference between the two treatment strategies – even at three years – was still very significant," Dr. Claude Lenfant, director of the National Heart, Lung and Blood Institute, said in the news release.

The trial initially was designed to recruit 1,200 patients, but the Data and Safety Monitoring Board recommended that the study be stopped on April 7, after only 1,016 patients had been enrolled.

Enrollment of new patients stopped immediately, and the data were presented to AVID investigators on April 9-10. At that time, investigators began informing participants of the results.

A clinical trial is designed to have periodic review of the data so that the trial can be stopped as soon as the objective is reached, Wathen said.

The results of the AVID trial illustrate the need for randomized clinical trials to determine the best therapy, Wathen said.

"Prior to this study, many physicians thought they knew what was best, and we now know that half of them were wrong," Wathen said. "Before the trial began, a poll of cardiologists was conducted that found about half of them believed that drugs would be more effective than the device. So this points up the extreme importance of randomized clinical trials."