The drug-eluting stent (DES) market has been hit hard over the past year or more with reports of potentially deadly clots forming in such stents.

Now, a new meta-analysis study published in The Lancet, a London-based medical journal, may help ease safety concerns about the popular, yet frequently debated technology. The analysis of 38 randomized controlled trials involving more than 18,000 patients found that the death risks associated with DES and bare-metal stents (BMS) are about the same.

However the findings of the analysis, which compares the only two FDA-approved drug-eluting stents — the Cypher from Cordis (Miami Lakes, Florida) and the Taxus from Boston Scientific (Natick, Massachusetts) — does not bode well for the Taxus stent.

The data suggests that patients who received the Taxus stent were a bit more likely to suffer heart attacks than those who received the Cypher. The research also shows a slightly elevated risk of potentially deadly clots forming in Taxus more than 30 days after implantation, compared with bare-metal stents, while Cypher patients did not run that risk, according to the data. Also, fewer Cypher patients needed follow-up procedures to deal with a recurrence of their coronary blockage.

Christopher Allman, executive director of corporate communications at Cordis, told Medical Device Daily that the 38 trials included in the analysis were funded from different sources. Some of the trials, such as REALITY, SIRIUS, E SIRIUS, RAVEL, were Cordis-funded, he said. The Swiss National Science Foundation funded the meta-analysis of these trials.

“As the largest and most comprehensive analysis done to date for drug-eluting and bare metal stents, we believe physicians and patients will find these results support the long-term safety of drug-eluting stents, but they also clearly show the differences between the two drug-eluting stents, the Cypher stent and the Taxus stent,” Allman said.

But Donald Baim, MD, chief medical and scientific officer for Boston Scientific, said in a statement provided by the company to MDD that the meta-analysis failed to reflect that Taxus was compared in its major trials with a better-performing bare-metal stent (the Express) than Cordis, a Johnson & Johnson (New Brunswick, New Jersey) subsidiary, chose for the Cypher trials. The Cypher was compared to the BX Velocity stent, Baim said.

The Bx Velocity had higher rates of repeated revascularization at four years and higher rates of stent thrombosis than the Express stent used in the Taxus trials, Baim noted.

Also, Baim said, two of the major comparisons with bare-metal stents in the Boston Scientific trials focused on smaller arteries and longer blockages than those tested in Cordis’ trials — conditions where risks of complications would presumably be higher.

“The attempt to force the two different BMS to be equal in the network meta-analysis distorts the estimate of how Cypher and Taxus compare, and leads to the false conclusion that Taxus has 2.7 times as much late-stent thrombosis as Cypher, and 1.4 times as much repeat revascularization as Cypher,” Baim said. “These estimates are not valid, and the Stettler paper actually admits that ‘Criteria for consistency of the network were satisfied for all outcomes except stent thrombosis and target lesion revascularization,’ indicating that the indirect inferences did not even agree with the comparatively small number of direct comparisons included in creating the ‘network.’ This indicates that those indirect comparisons are not to be relied on.”

In the U.S., Taxus controls about 54% of the DES market. Sales of both devices have fallen about 40% in the last year. Medtronic (Minneapolis) and Abbott Laboratories (Abbott Park, Illinois) are anticipating approval to enter the domestic DES market next year.

When asked what impact Cordis expects the meta-analysis to have on Cypher sales, Allman declined to speculate, noting that comments about sales and market share are discussed in the company’s quarterly earnings calls.

Charles Rudnick, a spokesman for Boston Scientific, also declined to comment on the study’s impact on the Taxus, instead pointing to Baim’s statement on the study.

David Kandzari, chief medical officer for Cordis, said in a statement that the study “significantly enriches the large body of evidence that interventional cardiologists have at their disposal to make the right choice for their patients” and clarifies the differences between Cypher and Taxus.

The mortality rates were similar for all three stents: hazard ratios (HR) were 1.00 (95% credibility interval 0.82 to 1.25) for the Cypher vs. bare-metal stents, 1.03 (CI 0.84 to 1.22) for the Taxus vs. bare-metal stents and 0.96 (CI 0.83 to 1.24) for the Cypher vs. the Taxus, Cordis noted.

“This large set of data indicates that the mortality associated with drug-eluting stents and bare-metal stents is comparable. Recent concerns about increases in mortality associated with drug-eluting stents are not supported by this analysis assessing long-term outcomes,” said Christoph Stettler, MD, from the University of Bern (Switzerland), one of the authors of the study. Stettler is with the Department of Endocrinology, Diabetes and Clinical Nutrition there.

“These results have also led us to conclude that the Cypher stent is clinically superior to bare-metal stents and the Taxus stent when the safety and effectiveness outcomes in this analysis are taken into account,” said Peter Juni, MD, also an author of the study. Juni is head of the Division, Clinical Epidemiology and Biostatistics, at the University of Bern.

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