In anticipation of receiving FDA approval by year’s end for its Endeavor drug-eluting stent (DES), Medtronic presented its Endeavor IV clinical trial findings this week at the Transcatheter Cardiovascular Therapeutics meeting in Washington, D.C. In response, a panel of cardiologists questioned the methods of the study and discussed the safety of the stent.
The “drug release [of Endeavor’s Zotarolimus] is more rapid” than its competitors, Cordis and Boston Scientific, because “most of the drug is released in 14 days,” said
Martin Leon, MD, of Columbia Medical Center in New York City who represented on Medtronic’s behalf. He did, however, concede that Endeavor “needs more and longer studies.”
The Endeavor IV clinical trial included 1,548 patients, 773 of which had the Endeavor stent implanted, and the other 775 who had the Boston Scientific’s Taxus stent implanted, according to Leon. The vessel diameter was between 2.5mm and 3.5mm. The primary endpoint for the study is target vessel failure (TVF) at nine months. The secondary endpoints included the target vessel revascularization (TVR) and target lesion revascularization (TLR) at nine months.
Of 144 patients who received an Endeavor stent, 19 patients, or 13.3 percent, had an occurrence of in-stent restenosis. For 135 patients with the Taxus stent, nine patients, or 6.7 percent, had an occurrence of in-stent restenosis.
Leon reported that the primary endpoint at nine months for TVF was 6.6 percent for Endeavor and 7.2 percent for Taxus. He said there was significant TVF difference at 12 months, but “Endeavor’s results remain lower.”
For the secondary endpoints, 5.4 percent of the patients with Endeavor at nine months experienced TVR while 4.9 percent of patients with Taxus experienced TVR at nine months. For the Endeavor results, 4.1 percent of patients experienced TLR at nine months with Endeavor, while 2.7 percent of patients with Taxus experienced TLR.
In addition, two patients implanted with the Endeavor stent died, while no patients implanted with Taxus died. Leon stressed that these deaths were not attributed to the stent.
Leon concluded that Endeavor reduced peri-procedural complications, and Endeavor’s statistics were similar to Taxus in its overall safety profile for larger complications such as death and myocardial infarctions (MI).
In response to Leon’s presentation, Patrick Serruys, MD, chief of interventional cardiology at Thoraxcenter-Erasmus University in Rotterdam, Netherlands, said that the Endeavor study had “obvious conflicts,” and questioned the methodologies of the study.
Serruys said Endeavor met its non-inferiority primary endpoint of TVF at nine months in comparison to the Taxus stent. However, Serruys disagreed with that method of TVF as a sole primary endpoint, because he believed the primary endpoint should be a composite of TVR, death and MI as well.
Serruys cited data from a European clinical study, which consisted of 1,490 patients, 749 of which had Endeavor implanted and 741 of which had Taxus. In overall cardiac-related deaths, four patients died for each of the stents. Two Endeavor patients had a Q-wave MI, and only one with Taxus. In Endeavor patients, 34 experienced TLR, 47 experienced TVR and 50 experienced TVF. In comparison, with Taxus patients, 24 experienced TLR, 50 experienced TVR and 47 experienced TVF.
In a different Swedish Coronary Angiography and Angioplasty Registry study, out of 2,497 patients, Endeavor had the highest rate of restenosis, followed by Taxus, according to Serruys.
In conclusion, Serruys reiterated his skepticism of about Endeavor’s efficacy.
In a panel discussion of six cardiologists that immediately followed the presentations, the physicians discussed whether Endeavor is safer. According to Jean Marco, MD, of Clinique Pasteur in Toulouse, France, who is currently implementing the CE Mark-approved Endeavor said it is “similar in safety to other stents.” Alexandra Lansky, MD, a clinical cardiologist at NewYork-Presbyterian Hospital/Columbia Medical Center in New York City, said that for “low risk patients, the device is safe, but it becomes more questionable for more complex patients.” Giulio Guagliumi, MD, of Ospedali Riuniti di Bergamo in Bergamo, Italy, said “we still have to collect big numbers.” He added that he “was little a surprised that stent thrombosis isn’t lower than Taxus. While six incidents in Endeavor and one in Taxus isn’t