Further research on defibrillator candidates called for
Research has shown that implantable cardiac defibrillators can save the lives of certain patients.
However, two articles published recently in the New England Journal of Medicine illustrate the need for further research to determine which patients are most likely to benefit from the devices (ICDs), say Vanderbilt cardiologists involved in the studies.
One of the articles reported the results of the landmark Anti-arrhythmics vs. Implantable Defibrillators (AVID) trial, which clearly demonstrated the mortality-reducing benefits of ICDs in patients with a history of life-threatening ventricular arrhythmias. VUMC was the only center in Tennessee among the 50 participating centers across the country.
The other trial studied ICDs in patients with severe heart disease who underwent elective coronary artery bypass graft (CABG) surgery. Nicknamed the CABG Patch Trial, this study found no difference in survival between those who received an ICD and those who did not. Dr. Jeffrey N. Rottman, associate professor of Medicine, was among the investigators in the trial, which was conducted at 30 centers in the United States and Germany.
"The results of these two studies are not inconsistent at all because they involved very different patient populations," said Rottman, who joined the Vanderbilt faculty earlier this year.
"ICDs decrease mortality in certain patients ‹ that has been very well established ‹ but it is not true for all patients at high risk of cardiovascular death. We still need to do a very careful and thoughtful job of picking out those patients for whom the benefits will outweigh the risks. We still have a lot of work to do from a research standpoint."
Results of the AVID trial were so dramatic that the National Institutes of Health called an early halt to the study last spring. The study found a nearly 25 percent reduction in deaths among patients with ICDs compared to those treated with medication. 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 NIH said.
Since the trial was stopped, participants who had been randomized to medication have been offered an ICD, and most have had an ICD implanted, said Dr. Mark S. Wathen, assistant professor of Medicine and principal investigator in the trial at VUMC.
The results are beginning to change clinical practice, Wathen said, with ICDs now becoming the first choice for many patients with ventricular fibrillation or ventricular tachycardia.
As a result, the length of hospitalization is dramatically reduced, from an average three weeks when a patient is put on medication to six days and decreasing, Wathen said.
"Because it's a life-or-death issue for these patients, we keep them in the hospital while we determine the medication and dosage that is most effective," he said.
The CABG Patch trial involved patients who had not developed an arrhythmia but whose heart disease was severe enough that they were at high risk of developing a life-threatening arrhythmia.
"The patients had an expected mortality rate of about 20 percent over the next two years, and it was thought that about half those deaths would be sudden — due to an arrhythmic event," Rottman said.
The patients were randomized: only half received the ICD as part of their elective coronary artery bypass graft (CABG) surgery. Because the ICD implant was performed in the context of scheduled cardiac surgery, no additional procedure with its corresponding risks was necessary.
"Mortality would have been expected to be high for these patients, and it was high, but it was not significantly different between the two groups," Rottman said.
Speculation is that perhaps the bypass surgery itself already offers protection against arrhythmias and placement of an ICD provides no added benefit, Rottman said.
"What we don't know at the moment is the role of surgical revascularization in protecting against arrhythmias," he said. "It is possible that the CABG surgery itself protected against future arrhythmias.
"An alternative is that only a small number of patients in the CABG Patch Trial were at high risk of future arrhythmias. We suspect that the occurrence of spontaneous heart rhythm abnormalities or the ability to provoke these abnormalities on testing might select a patient population more likely to benefit from ICDs," he said.
"A follow-up study will help in telling us whether we picked the 'wrong' patients or inadvertently picked the right therapy in CABG Patch."