Medical Device Daily Associate

In the wake of recent concerns about the long-term safety of drug-eluting stents (DES), including presentations last month at the World Congress of Cardiology (WCC; Sophia Antipolis, France) (Medical Device Daily, Sept. 6, 2006), an editorial just published on the web site of the American College of Cardiology (ACC; Washington) will add fuel to that fire. It charges that 2,000 patients are dying needlessly each year as a result of DES use.

The guest editorial, “Drug-eluting stents: An Ounce of Prevention for a Pound of Flesh,” said patients face a lower risk if treated with older, less costly, bare-metal stents (BMS) that might work, in many cases, just as well.

Written by Sanjay Kaul, MD, and George Diamond, MD, of Cedars-Sinai Medical Center (Los Angeles), this is the latest expression of concern about the risks of fatal blood clotting and serious heart attacks associated with DES.

”I think the debate here is not the drug-eluting stent vs. the bare metal stent,” Kaul told Medical Device Daily. “There’s a bigger debate here, and that is our obsession with revascularization as the primary therapy for treating stable angina.”

He said that drug therapy should be the first avenue for treating chronic stable angina “and only in those who don’t respond to [drug] therapy should revascularization therapy — whether stenting, angioplasty or bypass surgery — be offered.” He said that in a “quick fix society,” patients demand that approach, and “we are too eager to please them.”

In the U.S., the devices are sold by Boston Scientific (Natick, Massachusetts) and Johnson & Johnson (New Brunswick, New Jersey) via its Cordis (Miami Lakes, Florida) business.

Last month at the WCC meeting, results of a meta-analysis of past clinical trials of first-generation DES showed that DES-implanted patients had a greater risk of heart attack or death than patients BMS-implanted. The increased risk was greatest for J&J’s Cypher stent, at a statistically significant 38%, said Edoardo Camenzind, MD, of University Hospital (Geneva, Switzerland).

For Boston Scientific’s Taxus stent the increased risk was 16%, a figure not meeting statistical significance.

The actual risk of death or heart attack was still low in both groups, at 6.3% for patients given Cypher and 2.6% for Taxus. But because DES is so widely used, thousands of patients could be affected, Camenzind noted.

Kaul said that research suggests the use of the DES increases the risk of clotting by 0.6% annually, compared with BMS-implantation.

With more than one million Americans annually receiving the stents, and at least 80% of them getting DES devices, this works out to an additional 2,160 deaths each year, the doctors calculated. The figure assumes that 45% of the people who suffered such clots had died.

“It’s eerily reminiscent of Vioxx,” Kaul told the New York Times, referring to the popular painkiller that Merck (Whitehouse Station, New Jersey) withdrew from the market in 2004 after being linked to heart attacks. “Initially we didn’t see the signal because the incidence is so rare.”

Kaul said that DES is the proper application for many patients, but that the devices are used far too often in cases where clinical data suggests that BMS use or long-term drug therapy is safer. Only about 20% of DES devices are being inserted in patients who have the kinds of conditions studied in the clinical trials that led federal regulators to approve them, he said.

Kaul told MDD that he is, by nature, a skeptic and that he never got caught up in the DES hype.

He noted that the clinical benefits of DES relative to restenosis and target vessel revascularization (TVR) have been overestimated. For example, he said the TVR rates in the BMS control group were nearly 50% higher in the DES trials than that observed in contemporary interventional trials or in “real-world” clinical practice.

Kaul said he attributes the too-rapid integration of DES into clinical practice in the U.S. to a perfect storm of factors: device companies seeking larger profit margins to support the expense of clinical trials, regulatory approvals and marketing; the pressure of career advancement via rapid research and publication; the drive to feed insurance companies with the data that will drive reimbursement; and hospitals, physicians and patients all wanting cutting-edge treatments and technologies.

“Together,” the authors write, “all these individually understandable incentives conspire to introduce promising new technology too quickly into the medical marketplace and to encourage its rapid overutilization. It is not at all surprising then that conflicts should exist between clinical practice and its evidentiary support, and that many DES interventions are thereby insufficiently justified. . . . [I]t appears that the rules regarding use of DES, while justifiable to combat the knotty problem of restenosis (‘an ounce of prevention’), have inadvertently led to the new and even more intractable problem of late stent thrombosis (‘a pound of flesh’).”

Kaul noted declining use of DES at his hospital, from 95% a year ago to about 80%, “and continuing.”

He said the “real world restenosis rate” is not nearly as high as the off-label uses of the devices would indicate, and that the real rate of use of these devices should be in the10% to 15% range — even lower than the 20% approved by the FDA — as a “bail out” for those patients who present with restenosis following BMS.

These numbers, he said, may further be reduced since those patients who are unable or unlikely to comply with the long-term dual antiplatelet therapy necessary with these devices “should never be given a drug-eluting stent.”

He also suggested that for left main disease and multivessel disease, especially diabetics, coronary artery bypass surgery should remain the treatment of choice, until randomized data prove the effectiveness and safety of DES in these conditions.

Other doctors appear to be backing this trend. Last week, Merrill Lynch analyst Katherine Owen published a survey of 50 interventional cardiologists who implant the devices, finding that 42% said they may implant fewer DES devices, 30% still waiting for more evidence before making a decision.

Based in part on the response, Owen cut her expected penetration of DES in the 2007 U.S. market to 80% from a previous projection of 85%, or to $2.74 billion in sales from $2.92 billion.

And she noted that the Transcatheter Cardiovascular Therapeutics conference later this month in Washington likely will raise further DES concerns.