Drug-eluting stents now dominate most applications of coronary artery stenting because they dramatically cut the rate of restenosis. But a new issue has emerged: late thrombosis.
Until more data are collected to better define the late-thrombosis risk, concern about this complication will haunt drug-eluting stents and dampen their use.
Late thrombosis occurs when a thrombus forms within a stent and abruptly closes the coronary artery a month or more after the stent was placed—a time when bare-metal stents are generally believed to have become a benign part of a patient's vasculature.
“Late thrombosis has been extremely rare with bare-metal stents,” noted Mark J. Eisenberg, M.D., an interventional cardiologist at McGill University in Montreal.
That's why a report of four cases of fatal, late thrombosis in patients with drug-eluting stents in The Lancet last October caught cardiologists' attention. Even more compelling were the circumstances that tied the four cases together. In every patient, the abrupt occlusions appeared about a year after the stents were placed, and soon after the patients stopped long-term aspirin therapy (Lancet 2004;364:1519-21).
A team of physicians from the Thorax Center in Rotterdam, the Netherlands, and from the Washington Hospital Center published the clinical details of four patients who developed stent thrombosis 11-14 months after receiving a drug-eluting stent. Three patients had anterior myocardial infarctions, while the fourth manifested chest pain. Two patients had sirolimus-eluting stents (Cypher), and the other two had paclitaxel-eluting stents (Taxus). When the stents were placed, dual platelet-inhibitor therapy with aspirin and clopidogrel was used for 3-6 months, followed by aspirin-only treatment. In all four cases, the thrombosis occurred 4-14 days after aspirin was stopped (one patient was also still taking clopidogrel, which was stopped along with aspirin). In three cases, the antiplatelet drugs were stopped prior to surgery.
The risk of late thrombosis is based on the same properties that let drug-eluting stents block restenosis. As explained by Dr. Eisenberg in a comment that accompanied the four case reports, bare-metal stents become endothelialized within a few weeks of implantation, which is why their rate of late thrombosis is so low. In contrast, drug-eluting stents delay endotheliazation, which is why dual platelet inhibition is routinely used for up to 6 months.
“I've changed the way I use drug-eluting stents” because of the reports of late thrombosis, said Deepak Bhatt, M.D., an interventional cardiologist at the Cleveland Clinic. “If I know a patient will have surgery soon, I ask myself if he or she really needs the coronary stent before surgery. I try to defer stenting when possible. If stenting must be done immediately, then I tend to use bare-metal stents. I think most of my colleagues would too,” Dr. Bhatt said in an interview.
Another approach that some cardiologists have taken is to put even greater emphasis on anti-thrombotic treatment, without cutting back on using drug-eluting stents. “The reports of subacute stent thrombosis have not prompted me nor any other interventional cardiologist who I know to change practice, other than to extend the duration of dual, oral antiplatelet therapy,” said Herbert D. Aronow, M.D., director of the cardiac catheterization laboratories at the Veterans Affairs Medical Center in Philadelphia. “I typically continue aspirin and clopidogrel through surgery, if possible. When not possible, I try to continue aspirin alone. If both aspirin and clopidogrel must be stopped, I typically delay surgery until the risk of stent thrombosis is much lower, and I balance the need for surgery against the risk of stent thrombosis.”
“If we find that the late thrombosis rate is two- or threefold higher [with drug-eluting stents, compared with bare metal stents] after stopping dual antiplatelet therapy or 1 year after an implant, then we will need to reconsider … our use patterns of drug-eluting stents until we develop safer systems,” Martin B. Leon, M.D., said at the American Heart Association scientific sessions last November in New Orleans. “Safety is more important in this case than antirestenosis efficacy,” added Dr. Leon, associate director of the Center for Interventional Vascular Therapy at Columbia University in New York.
From the time drug-eluting stents were introduced, physicians were concerned about an increased incidence of late thrombosis. Last year, Dr. Eisenberg and his associates did a metaanalysis of data collected in 11 trials that had compared sirolimus- and paclitaxel-eluting stents with bare-metal stents in a total of 5,103 patients (Lancet 2004;364:583-91). The results showed that the pooled rate of stent thrombosis was 0.5% among the patients who received bare-metal stents and 0.7% among those who received drug-eluting stents, a nonsignificant difference. But because the rate of thrombosis is low, even this large analysis did not have the statistical power to completely rule out a twofold difference in risk between the two stent types.