Clinical Trial to See if Small Doses of Radiation can Prevent Re-Clogging of Blood Vessels After Angioplasty
DURHAM, N.C. –- In the hands of cardiologists, tiny balloons on the ends of hair-like wires open blocked coronary arteries of more than 1 million Americans each year.
The procedure is called balloon angioplasty, and as effective as it has been in keeping heart patients from undergoing major and costly surgery, up to one-half of all these treated coronary arteries tend to re-clog within six months, a process known as restenosis.
Cardiologists thought they could significantly reduce restensosis rates by using tiny flexible girders called stents inserted into the arteries to hold them open after angioplasty. Stents reduced the rate of restenosis but one-fifth of the arteries still clogged again.
Cardiologists now hope that a new approach, using radiation either with or without stents, can reduce the restenosis rate even more. Based on preliminary studies on a small group of patients, minute doses of radiation administered for as little as five minutes at the time of angioplasty shows such promise.
Thirty-two centers, including Duke University Medical Center, are now enrolling heart patients in a FDA-approved clinical trial to find out if radiation will prove to be the weapon to attack angioplasty's Achilles Heel.
"While the data from previous trials are preliminary, it does appear that radiation has the potential to significantly reduce the rate of restenosis after angioplasty," said Duke cardiologist Dr. Michael Sketch, principal investigator for the trial at Duke. "Radiation has the same potential for making a huge impact on angioplasty as stents have done."
In angioplasty, a tiny balloon is threaded through the arteries to the site of blockage, where it is inflated, pushing the atherosclerotic plaque to the side. While this process opens a larger channel for blood to flow through, it also stimulates the abnormal growth of new endothelial cells, which can then re-block the treated artery. This process is called neointimal hyperplasia.
Researchers believe that radiation, when delivered at the same time the artery is re-opened, interferes with the endothelial cells proliferative response.
"A recent study involving 35 patients at Emory University showed that only11 percent of the patients showed restenosis after radiation treatment, while 42 percent of the control group had restenosis," Sketch said. "While this effect was shown in a very small number of patients, the results are promising, and exciting."
That study, called BERT (Beta Energy Restenosis Trial), as well as the current multi-center trial, involves the Beta-Cath system developed by the Novoste Corp., Norcross, Ga.
In the radiation procedure, after the balloon angioplasty device is withdrawn from the patient, a slender hollow tube is inserted through the artery to the site of treatment. Once at the site, small amounts of radiation is sent through the tube in a liquid solution to the site, where it stays for about five minutes. At no time does the solution leave the device and come into contact with tissue, Sketch said.
The radiation procedure adds about 10 minutes to the typical angioplasty.
According to Duke radiation oncologist Dr. Greg Sibley, a co-investigator in trial, it is important to note that beta radiation is used in the current trial. Beta is a form of radiation that is extremely safe for both patients and health care workers, Sibley said, because a significant amount of radiation only travels a distance of a few centimeters from the source, meaning that surrounding tissues are not affected. It also means that health care workers and patients don't need cumbersome protective clothing, and special containment facilities aren't needed for the product.
While researchers do not know the precise reasons why radiation has a positive effect on benign cellular proliferation, Sibley said radiation has been used successfully in treating other conditions involving abnormal (non-cancerous) cell growth.
"Beta radiation has been used for decades to treat keloids, large growths of scar tissue on the skin caused by proliferation of normal tissue in response to an injury," Sibley explained. "If you give a small amount of radiation after removing keloids, they seldom come back. We're hoping the same will principal is at work in the coronary vessels."
Radiation is also being used at Duke to prevent the abnormal proliferation of bone cells after total hip replacement, and will be soon studied as a means of preventing blockage of hemodialysis access grafts.