The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has stopped a clinical trial comparing two treatment strategies for patients with life-threatening heart arrhythmias: an implantable cardiac defibrillator versus antiarrhythmic drug treatment. The Institute's action was prompted by a significant reduction in deaths in the group of patients whose arrhythmia (abnormal heart rhythm) was treated with a defibrillator.
"This landmark study is the first large controlled study to show that implantable cardiac defibrillators improve overall survival in patients with serious ventricular arrhythmias," said NHLBI Director Dr. Claude Lenfant. "We've known for some time that these devices stop arrhythmias and restore normal heart rhythm, but it has not been known -- until now -- whether they improve overall survival," he said.
In the Antiarrhythmics Vs. Implantable Defibrillators (AVID) Trial, patients with a history of ventricular fibrillation (VF) or serious ventricular tachycardia (VT), both of which are life-threatening, were randomly assigned to receive treatment with either a defibrillator or with a drug -- amiodarone or sotalol. The objective of the study was to determine which strategy offered the greatest reduction in mortality. Some patients in each group were given other drugs as needed, including beta-blockers, aspirin, and ACE-inhibitors. Since AVID began as a pilot study in 1993, 1016 patients, average age 65 years, have been studied at 50 clinical sites in the U.S. and Canada. Before the study was stopped, the AVID investigators had planned to recruit 1200 patients into the trial.
Half of the patients in the study had VT and half had VF. After one year, patients in the defibrillator group experienced a nearly 38 percent reduction in deaths compared to the group of patients taking an antiarrhythmic drug. The defibrillator group had about a 25 percent reduction in deaths in years two and three. Dr. Lenfant stressed, "Even though the relative benefit for implantable defibrillators compared to drugs declined over time, the difference between the two treatment strategies -- even at 3 years -- was still very significant. If we apply the results of AVID to the population at risk, over 1000 lives would be saved each year in the U.S."
Of the estimated 350,000 sudden cardiac deaths that occur in the U.S. each year, most are thought to be due to VF and VT. In ventricular fibrillation, the ventricles quiver in an irregular chaotic way so that no blood is pumped out, and the body, particularly the brain, is deprived of oxygen. In ventricular tachycardia, the heart beats too fast because of rapid electrical impulses starting in the ventricles, which also decreases bloodflow and deprives the body of oxygen. Heart attacks and cardiomyopathy (heart muscle disease) are the most common causes of ventricular tachycardia and ventricular fibrillation.
Currently, patients with VT and VF are treated with either an antiarrhythmic drug such as amiodarone or sotalol or with an implantable cardiac defibrillator. Both treatment options are used widely although there have been no large randomized studies comparing their efficacy.
"The results of this study will streamline the therapeutic approach for patients with life-threatening arrhythmias," said Dr. Douglas Zipes, chair of the AVID Steering Committee, which was responsible for the scientific conduct of the study, and Distinguished Professor of Medicine and Chief of Cardiology, Indiana University School of Medicine. "It is clear that these patients should be treated first with an implantable cardiac defibrillator," he said.
Patients who have ventricular fibrillation or ventricular tachycardia and are currently taking an antiarrhythmic drug should talk to their physician about an implantable cardiac defibrillator. Patients currently enrolled in the AVID trial are being notified by phone and registered mail. The AVID investigators will discuss treatment options--including an implantable defibrillator -- with those patients who received antiarrhythmic drugs during the study.
"The implantable cardiac defibrillator is like having an emergency room implanted in your chest," asserted Dr. Zipes. "The device will monitor your heart rhythm and respond with appropriate therapy," he said.
An implantable cardiac defibrillator does not prevent dangerous arrhythmias from starting, but it recognizes them and works to restore a normal rhythm by pacing the heart or giving an electric shock to the heart. The devices also store the information collected so that it can be evaluated by physicians. In some future models, the information will be sent to physicians over the phone. Most of the devices used in the AVID study were implanted without open chest surgery. The procedure is done under anesthesia by putting an electrode into the heart through a vein near the collarbone. A second larger wire may also be placed under the skin of the chest. These wires are then connected to the defibrillator that is placed under the skin of the abdomen or near the shoulder.
The AVID cost data shows that the average hospital charges for a defibrillator implantation are $66,600. The average charges for monitoring a patient who is in the hospital for administration of anti-arrhythmic drugs is $34,000. Dr. Zipes speculated that the defibrillator strategy may become less costly over time. "Ultimately the device strategy may become less expensive because it will require fewer days in the hospital compared to patients on antiarrhythmic drugs -- who must be hospitalized for the initial administration of these drugs," he said. The AVID investigators are currently evaluating the cost-effectiveness and quality of life of the two strategies.
The AVID study was stopped on April 7 after a review of the data by the study's Data and Safety Monitoring Board (DSMB). The DSMB's recommendation to halt the study was approved by Dr. Lenfant and enrollment of new patients ceased immediately. On April 9 and 10, the data were presented to the AVID investigators at a meeting of the Steering Committee. On April 10, investigators began informing patients about results of the study.
For more information, or to interview Eleanor Schron, the NHLBI AVID project director, please call the NHLBI Communications Office at (301) 496-4236. To contact Dr. Zipes, please call (317) 630-6640.
NHLBI press releases, fact sheets, and other materials are available online at http://www.nhlbi.nih.gov/.