Medical Device Daily

Depending on whether you are a glass-half-empty or glass-half-full type, the wealth of data and commentary just published in the New England Journal of Medicine on drug-eluting stents (DES) compared to their less costly bare-metal stent (BMS) cousins can be extrapolated as either positive or negative.

In other words: the data are largely inconclusive, the reported studies disagreeing as to statistical advantage or disadvantage.

This must have been disappointing to DES makers Johnson & Johnson (J&J; New Brunswick, New Jersey) and Boston Scientific (Natick, Massachusetts) — the two current players in the U.S. market — obviously hoping that this issue of NEJM would help clear up the controversy surrounding DES devices over the past year. Instead, the data — offered in five articles, two commentaries and an editorial — may only muddy the waters further.

These new studies might offer reassurance that the stents are safe. Or they may indicate that the stents should be used much more rarely. Or, on the extreme end of the half-empty-to-entirely empty scale, they represent a failure of medical device regulation.

In the past year, some studies have shown that in rare instances deadly blood clots may form with DES use, causing heart attacks or even death, dropping sales for Boston Scientific and J&J.

An article on the NEJM studies in the New York Times yesterday said that recent earnings reports from those two companies suggest that DES use has leveled off and may even be waning. The article noted that cardiologists have shifted enough patients to BMD to cut the DES share to 73% from last spring's peak of about 88%.

Since DES devices cost about $2,200 apiece in the U.S. vs. about $800 for BMS, the Times estimated that the shift in use has cost the two companies close to $500 million in domestic sales alone.

All of the studies published online Monday by the NEJM were previously discussed at a meeting in December, organized by the FDA to review the data (Medical Device Daily, Dec. 12, 2006).

Some of the data shows increased risk when the stents are used as directed. But Gregory Curfman, MD, a cardiologist and editor of the NEJM, editorializes that when DES are used in FDA-approved ways, "we're free and clear." A caveat here: Patients need to take the blood-thinner Plavix for a year or more.

But Curfman and his colleagues in the NEJM editorial say that off-label use — about 60% of all use — further clouds the DES data waters.

DES "were approved for use in stable patients with relatively noncomplex coronary stenoses," they write, "but they have been used in many patients whose clinical features and coronary anatomy fall outside the original specifications." Such off-label use "has made assessments of stent safety beyond the setting of clinical trials more challenging."

Curfman also notes that while the FDA panel in December agreed that the use of antiplatelet therapy in the form of Plavix after placement of a DES, "the optimal duration of therapy has not been established yet."

Perhaps the most negative study data comes from a 20,000-patient analysis from Sweden showing an increased risk of death in patients implanted with a DES compared to a BMS up to three years after implantation.

In a statement of response, Boston Scientific criticized this study, saying that the data did not come from patients randomized to DES or BMS devices. It said that, instead, the study tracked patients from a national database and that the DES-implanted patients were sicker.

The Swedish researchers tried to correct for this difference, and some outside researchers have said the result is worrisome.

Gregg Stone, a professor of medicine at Columbia University (New York) and the author of an analysis of Boston Scientific's stent data published in the NEJM, said he is worried that doctors have pulled back too much from using DES, in even off-label uses. "I do believe it's going down too much," said Stone.

In a perspective piece in the NEJM, William Maisel, MD, of Beth Israel Deaconess Hospital (Boston) and the chair of the December FDA advisory panel meeting on DES, writes that in the Swedish registry stent selection "was not randomized among registry patients, so the observed differences may be due to confounding factors such as physician bias in stent preference. Thus, current data are inadequate for assessment of the relative benefit of off-label use of drug-eluting stents as compared with either bare-metal stents or coronary-artery bypass surgery."

"The Swedish registry data are provocative, but far from definitive," said Donald Baim, MD, chief medical and scientific officer for Boston Scientific in the company's response to the Swedish study. "The raw data showed no increase in death or heart attack for drug-eluting stents, and a small increase was suggested only after statistical adjustment was performed in an effort to correct for the significantly greater number of high-risk patients in the drug-eluting stent group. In addition, the counting of adverse events was restarted beyond the first six months, after drug-eluting stents have already provided their greatest benefit."

In a podcast that accompanied the journal articles, Steven Nissen, MD, a cardiologist at the Cleveland Clinic Foundation (Cleveland) and current president of the American College of Cardiology (Washington), presented an opposing view, saying that the Swedish study suggests that bigger clinical trials comparing the two types of stents are greatly needed

"If the Swedes are right, we will regret putting [DES] into individuals," Nissen said.

The ultimate question here is clear: Will publication of these data and commentaries in the NEJM alter the DES market?

In an audio conference sponsored by Medical Device Daily yesterday on "Unblocking the Truth About Coronary Stents," Deepak Bhatt, MD, associate director of the Cleveland Clinic Cardiovascular Coordinating Center (Cleveland), said he doesn't believe this latest data released by the journal will greatly alter physician practice.

"They're all well-done studies, but they all, in a sense, are reaching different conclusions, depending on how you're interpreting them," said Bhatt.

He suggested, however, that this latest batch of data will continue to focus attention on the questions surrounding DES.

"I don't think the issue is going to go away either," he said.

Bhatt said that the negative data over the past several months has somewhat impacted the utilization of DES, but only by about 5%-10% over the peak of DES use that he characterized as being "in the 90-plus-percent range."