TCT: Coronary Stent Makers Open Trial Databases to Quell Safety Debate

October 25, 2006

WASHINGTON -- The drug-eluting coronary stent industry has responded with some additional soothing statistics in efforts to calm fears about the long-term safety of the devices.

WASHINGTON, Oct. 25 -- The drug-eluting coronary stent industry has responded with some additional soothing statistics in efforts to calm fears about the long-term safety of the devices.

Stent makers Boston Scientific and the Cordis Corporation opened their clinical trial databases to so-called independent analyses, which found no increase in death or acute myocardial infarction for the stents, but did confirm a small late stent thrombosis risk.

With both the Cypher (sirolimus-eluting) and Taxus (paclitaxel-eluting) stents, the risk emerged after a year. For Cypher the stent thrombosis rate was 0.6% versus 0.0% for bare-metal stents (P=0.025). For Taxus, the one-year thrombosis rate was 0.7% versus 0.2% in the bare-metal stent group (P=0.033).

The death or myocardial infarction rate after four years was a non-significant 12.4% for Taxus versus 11.8% for controls (P=0.77) and for Cypher it was also non-significant at 11.6% versus 10.3% (P=0.39).

These analyses were presented the same day that Cordis, the Johnson & Johnson company that makes the Cypher (sirolimus-eluting) stent, reported that applying a new definition of stent thrombosis to its clinical data eliminated any significant safety differences between its device and base-metal stents.

Moreover, according to this latest pair of post hoc analyses, drug-eluting stents significantly reduced the rate of target-lesion revascularization and target-vessel revascularization (P<0.0001 for both Taxus and Cypher). This finding that further enhanced the drug-eluting stent safety profile because many of the deaths and MIs in the bare-metal groups were said to be associated with revascularization.

That was the message delivered yesterday of the Transcatheter Cardiovascular Therapeutics (TCT) meeting here by Columbia cardiologists Gregg W. Stone, M.D., and Martin B. Leon, M.D., of the Cardiovascular Research Foundation in New York, who are the TCT course directors

Again and again, Drs. Stone and Leon hammered home their conclusion that drug-eluting stents are safe, a conclusion they based on what they said was an analysis of the best data, the first time it has become available. Moreover, they said this analysis marked a new era of transparency in which industry was willing to open its proprietary databases to scrutiny by what they said were independent reviewers.

Dr. Stone, who was a principal investigator in the TAXUS I, II, IV, V, and VI six trials, said he had absolutely no connection with the Cypher clinical trials program, so he presented the Cypher analysis. He is also a consultant to and receives lecture fees from Abbott Vascular and he has an equity share in Xstent, Devax and is on the Devax board of directors.

Dr. Leon, who said he was a non-paid consultant to Boston Scientific, maker of Taxus, presented the Taxus analysis. He said was also principal investigatior for all off the Cypher studies.

Dr. Leon said today that Stuart Pocock, a professor medical statistics at the University of London, did the analyses that Dr. Leon and Dr. Stone presented.

Pocock said the stent thrombosis issue boils down to four important numbers. "In Cypher," he said, "after one year the number was five cases of stent thrombosis versus zero. On Taxus beyond a year the number was nine versus two."

In both cases, he said, "the numbers are borderline significant, but if you add them together that becomes 14 versus two and that is a P value of 0.001, which is overwhelmingly significant."

The combined drug-eluting stent thrombosis worked out to "an absolute risk of 1.8 events per 1,000 patient years of follow-up," Pocock said.

That risk, he said, was comparable to the risk seen with some drugs that, like drug eluting stents, have a small but significant risk, which was generally outweighed by a much greater benefit.

The new analyses of Taxus and Cypher clinical trials data were presented during a panel that also featured three studies first presented at the European Society of Cardiology meeting in Barcelona.

It was these three studies, all of which concluded that drug-eluting stents were associated with late stent thrombosis, that ignited the drug-eluting stent safety controversy. Two of those studies also concluded that the stents were associated with excess mortality and/or excess rate of myocardial infarction.