The pattern of some of the earliest cases of stent thrombosis in RESOLUTE All Comers suggested that it may have been caused more by operator failings and less by problems with the stent itself. During the study’s first 30 days, stent thrombosis occurred in nine ZES patients and one EES patient, making up most of the differential that wound up haunting the ZES arm through the next 2 years. "Stent thrombosis during the first 30 days is procedure related," and generally the stent itself plays no role, said Dr. Alan C. Yeung, professor of medicine and director of cardiac catheterization at Stanford (Calif.) University in Palo Alto.
"Whether it’s a real difference or a play of chance remains undetermined," commented Dr. Mitchell W. Krucoff, a professor of medicine and interventional cardiologist at Duke University in Durham, N.C. "These types of differences [21 patients versus 11 patients] are not certain at a statistical level." He called the question of a safety difference between the two stents "an open question," adding that "all the rest is superimposable" between the ZES and EES.
So if the ZES hopes to wrest any market share from the EES when it hits the U.S. market, it may need to have something to distinguish it, and that something may be an FDA-approved indication for treatment of coronary stenoses in patients with diabetes. At least that’s what Medtronic is hoping for. The company included that application in its submission to the FDA, Jason Fontana, Ph.D., senior director for clinical communication at Medtronic, said in an interview. If the ZES gets this indication, it will make the device unique. No other coronary stent now on the U.S. market carries that indication in its label.
"The diabetes subgroup was large enough, and the diabetes analysis was prespecified" in RESOLUTE US, Dr. Leon said in an interview. "If you include this subgroup, and the RESOLUTE All Comers diabetes subgroup, you have a robust enough population to justify consideration for approval, I think," he said.
"The results were quite substantial," with a 3.0% rate of target-lesion revascularization among the patients with diabetes, compared with a 2.0% rate for the entire main cohort of the study. "Usually you see more of a bump in patients with diabetes," he said. "To see a 3% repeat revascularization rate in patients with diabetes is very encouraging. I think if the stent gets this indication it may have an impact. It’s an important consideration."
But even if the diabetes indication works out, will interventionalists be swayed by that, or by the data?
"An issue is, to what extent can a single trial address a subgroup?" said Dr. Krucoff. "To what degree is there statistical guidance that in the real world [the ZES] would live up to this measure?"
"I don’t think I’d put a lot of emphasis of my decision-making on the [RESOLUTE US] data, because a problem with all [stenting] studies is that the rates are constantly improving, so the new device can appear to be better," said Dr. Prasad. "The study did not use a SYNTAX score to give us an idea of how complex the patients were. Unless we know about the complexity of the disease in the diabetes patients, I’m not sure we can call it a superior performance than what one would expect in today’s practice. Even if [the ZES] was approved for use in patients with diabetes, I don’t think in my practice I’d pick it to use in those patients. They’d need to do a randomized study in patients with diabetes to convince me" that it was better than the EES, Dr. Prasad said.
Dr. Serruys said he had no disclosures. Dr. Prasad said he had no disclosures. Dr. Leon said that he serves as an unpaid consultant to Abbott, Boston Scientific, and Medtronic. Dr. Yeung said that he serves on the scientific advisory board of Medtronic; he is also a consultant for Abbott Vascular, Boston Scientific, and Cordis, and has received research grants from Boston Scientific, Edwards, and Medtronic. Dr. Fontana is an employee of Medtronic. Dr. Krucoff said that he has been a consultant to or has received honoraria from Abbott, Biosensors, Cardiomind, Cordis Johnson & Johnson, Medtronic, Merck, Micelle, OrbusNeich, Prescient, Sanofi-Aventis, and Terumo.