Medical Device Daily

In just a few days a panel of federal health officials and outside experts will meet in Washington to scrutinize the safety of drug-eluting stents (DES), a growing controversy in the cardiovascular sector. Adding to the debate is a recent study led by the Cleveland Clinic (Cleveland) that found as much as a four- to five-fold increased relative risk for late thrombosis, or blood clot formation, in patients with DES compared to those with bare-metal stents.

The meta-analysis, published in the December issue of the American Journal of Medicine, is the first published analysis of its kind, according to the Cleveland Clinic.

Drug-eluting and bare-metal stents are commonly used to treat patients with coronary artery disease. There has been a growing body of evidence that drug-eluding stents, when compared to bare-metal stents (BMS), may increase the risk of blood clot formation long after they are implanted, potentially triggering a heart attack.

Deepak Bhatt, MD, associate director of the Cleveland Clinic Cardiovascular Coordinating Center and the senior author of the study, told Medical Device Daily that for an individual patient the risk of clotting after the drug-eluting stents are implanted is “very small.” But the analysis provides valuable information, he said, for the physicians implanting the stents as well as other physicians caring for the patients after the stents have been implanted.

“Our analysis found there is a small, but real, hazard of late stent thrombosis with drug-eluting stents more so than with bare-metal stents, likely in the setting of discontinuation of anti-clotting drugs,” Bhatt said. “This does not, however, mean that drug-eluting stents should not be used, as other studies have shown that they do significantly reduce the need for repeat procedures compared with bare-metal stents.”

Fourteen studies with 6,675 total patients were included in the analysis comprising nine sirolimus stent trials and five paclitaxel stent trials. Eight of the trials reported more than a year of clinical follow-up. The sirolimus trials mandated anti-clotting medication for at least two to three months and the paclitaxel trials required six months.

Bhatt said he believes the analysis provides useful information for the physician implanting the stent to consider and might encourage them to “just be a bit more cautious” when using drug-eluting stents. For example, if a patient has a higher-than-average risk of bleeding or a history of non-compliance with medication, the physician may want to consider using a BMS instead of a DES, he said. Similarly, if a patient is likely to face surgery in the coming year BMS may be a better choice because the patient’s surgeon will most likely stop their anti-clotting medication prior to surgery.

The analysis might also encourage the patient’s other doctors — such as their primary care physician or surgeon — to put some extra thought into their care or perhaps even consult the implanting physician before discontinuing their anti-clotting medication, Bhatt said.

“I think drug-eluting stents are really quite advanced in the treatment of cardiovascular disease,” Bhatt said.

But like any medical treatment, he said, there is a risk of side effects.

“The key is just proper patient selection and some care with the use of anti-clotting medication,” Bhatt said.

The analysis precedes an FDA Advisory Panel set to meet Thursday and Friday in Washington to discuss and make recommendations regarding issues related to stent thrombosis in coronary drug-eluting stents. The panel charged with evaluating the cardiovascular devices is likely to pay the most attention to products by the two makers with FDA-approved devices — Cordis (Miami Lakes, Florida), a unit of Johnson & Johnson (New Brunswick, New Jersey) and Boston Scientific (Natick, Massachusetts).

The debate concerning DES technology was a panel discussion at the annual scientific sessions of the American Heart Association (AHA; Dallas) in Chicago last month (Medical Device Daily, Nov. 15, 2006). During the AHA panel, David Williams, MD, of Rhode IslandHospital (Providence) reported on a comparison of 3,000 patients in the National Heart, Lung, and Blood Institute Dynamic Registry who received either DES or BMS. Though DES patients tended to have more complex disease, they had lower rates of mortality in-hospital and at one year. Heart attack was slightly higher in the DES group, but DES patients required less repeat revascularization. And the researchers supported use of DES “in standard clinical practice.”

Presenting the anti-DES position at AHA, Joseph Muhlestein, MD, professor of medicine at the University of Utah and director of research at LDS Hospital (Salt Lake City), reviewed a three-year comparison of the Cypher and Taxus stents, the two that are FDA-approved and the focus of the debate. That comparison showed an “all-cause” rate of death higher in DES patients than BMS and a greater rate of adverse events, such as heart attacks, and repeat revascularization procedures out to three years.

Earlier this year Cordis, maker of the Cypher stent, issued a study at the Transcatheter Cardiovascular Therapeutics (TCT) conference in Washington on what it called the multiple factors of stent-related thrombosis (MDD, Oct. 25, 2006). Its study showed that the Cypher stent is not associated with an increased overall risk of thrombosis when compared to BMS out to four years.

Bhatt said Cleveland Clinic’s analysis is based on a randomized clinical trial and he emphasized that more research on drug-eluting stents is needed.

Cleveland Clinic Heart & Vascular Institute is a world leader in diagnosis and treatment of cardiovascular disease and has been ranked No. 1 in the nation for cardiac care by U.S. News & World Report every year since 1995. Cleveland Clinic is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education.