The rate is much higher, they said, because earlier clinical trials that pegged the rate at about 1 percent enrolled a highly selective group of patients at high-volume academic centers. They said these patients are not truly representative of the mix of patients routinely treated by cardiologists in their practices.
The use of stents has taken off in the past decade, and it is estimated that up to 80 percent of the nearly 600,000 angioplasty procedures performed each year in the United States also involve the placement of a stent.
The major problem encountered by cardiologists using stents is the formation of a blood clot within the stent. To address this problem, various agents have been developed to keep platelets in the blood from clumping together, which has reduced the rates of clotting, or thrombosis, and increased the success rates of stent procedures.
"The conventional wisdom has been that in this modern era of anti-platelet therapy, the risk of stent thrombosis has been around 1 percent," said Dr. Thaddeus Tolleson, a cardiology fellow at the Duke Clinical Research Institute (DCRI). "When we looked at a different set of data, which we felt was more representative of what cardiologists actually see every day, the rate of stent thrombosis approached 3.5 percent.
"Stent thrombosis is a rare event, but when it happens, it is quite dramatic," Tolleson continued. "They usually occur within the first two weeks of a stent placement and typically involve a large infarction or sudden death. They are infrequent but catastrophic."
Tolleson prepared the results of the DCRI analysis for presentation Monday (Sept. 3) at the annual meeting of the European Society of Cardiology.
In the early trials of anti-platelet therapy during angioplasty, sicker patients with more severe coronary artery disease were typically excluded. For this reason, the Duke researchers combined the data from two clinical trials involving anti-platelet therapies designed expressly for these patients with acute coronary syndromes.
Specifically, they used data gathered from the SYMPHONY (Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events post-acute coronary syndromes) and Second SYMPHONY trials. Both trials, which compared the effectiveness of aspirin to a new class of "super aspirin" to prevent recurrent heart attacks, enrolled 15,904 patients at 716 hospitals in 35 countries. Of those patients, 4,641 went on to receive an angioplasty procedure followed by a stent placement.
"Using a group of patients who were diagnosed with acute coronary syndromes, the overall rate of stent thrombosis was 3.5 percent -- 2.1 percent in the SYMPHONY trial and 4.7 percent in Second SYMPHONY," Tolleson said. "These are the types of patients who were not included in earlier trials, but who can make up a significant percentage of a cardiologist's practice."
In addition, the data from the two trials showed that those who are at the highest risk for having stent thrombosis are patients with diabetes, who are elderly, who are female, or those who have had a prior heart attack or angioplasty procedure.
Ironically, it is the actual placement of the stent itself that seems to ultimately lead to thrombosis. When the stent is expanded within the artery, it inevitably causes irritation of the endothelial lining of the artery. The body responds to this as it would to any other injury – platelets arrive at the scene to initiate the healing process, which usually takes two to four weeks. However, in some patients, this natural response can provoke clots large enough block the stent.
"We will still continue to put stents into our patients with acute coronary syndromes, but as a result of this study, we will do it with a higher awareness that thrombosis is not as rare as we once thought," said Dr. Kristin Newby, a cardiologist at the DCRI and senior author of the study. "Will these findings change practice? Not immediately, but it should stimulate further studies on new treatments – both before and after stent placement – to lower these rates."
The new approaches could include giving patients anti-platelet agents for longer periods either before or after the procedure, as well as the development of a new class of stents impregnated with anti-clotting agents or even radiation, which has been shown to stem the proliferation of endothelial cells.
Newby was the principal investigator for both the SYMPHONY and Second SYMPHONY trials, which were funded by F. Hoffmann-La Roche, Ltd., Basel, Switzerland. The DCRI supported Tolleson's analysis of the data.
Note to editors: Dr. Tolleson can be reached at 919-668-8948 or tolle004@onyx.dcri.duke.edu; Dr. Newby can be reached at 919-668-8805 or Newby001@mc.duke.edu. A color photograph of Tolleson is available at http://www.dukemednews.duke.edu/gallery/detail.php?id=231 and a color photograph of Newby is available at http://www.dukemednews.duke.edu/gallery/detail.php?id=230.