Washington, DC - Twelve months after undergoing stent implantation, patients treated with the investigational Xience V everolimus-eluting stent still are having fewer major adverse cardiac events (MACE), as compared with those treated with the market-approved Taxus paclitaxel-eluting stent, researchers announced during the TCT 2007 meeting. Presenting the results, Dr Gregg Stone pointed out that this is the first time a drug-coated stent has proved itself superior to a device already on the market and widely in use.

Dr Gregg Stone

The stent manufacturer, Abbott, is hoping to go before the FDA's circulatory system devices advisory panel in late November to make its case for approval, but industry watchers have speculated the company may not have enough follow-up data to win over the panel. Whether the positive results of SPIRIT III against the Taxus will convince panel members to overlook the lack of long-term data remains to be seen.

A meeting of the panel is tentatively scheduled for November 29-30, but the topic of this meeting, or even a confirmation that it will actually take place, has yet to come from the FDA.

SPIRIT III involved 1002 patients at 65 US sites randomized in a 2:1 manner to the XIENCE V stent or the Taxus stent. After implantation, patients were treated with clopidogrel 75 mg once daily for at least six months. The primary end point of the study was in-segment late loss at eight months, and the secondary end point was ischemia-driven target vessel failure (TVF), a composite of cardiac death, MI, target lesion revascularization (TLR), and target vessel revascularization (TVR) at nine months.

As previously reported by heartwire, nine-month results showed in-segment late loss for the Xience V stent to be half that of the Taxus, while TVF was noninferior to Taxus. MACE rates, driven by a strong reduction in TLR, were significantly better at nine months. Now, with an additional three months of follow-up, MACE rates for the XIENCE stent were significantly lower than those of Taxus, at 5.8% for Xience and 9.9% for Taxus: an absolute difference of 4.1% and a relative reduction of 43%. Those lower MACE rates were due to numerically fewer periprocedural MIs and fewer TLR procedures between six and 12 months, Stone said.

The 12-month SPIRIT III results have been trumpeted during the meeting and received wide press coverage. Stone, however, was careful to point out that SPIRIT III cannot yet answer burning questions about stent-thrombosis risk for the new stent. In the trial, stent thrombosis occurred in five XIENCE V-treated patients and in two Taxus-treated patients, according to the trial protocol's definition of stent thrombosis. Using the Academic Research Consortium's definition of definite/probable stent thrombosis, these rates were seven for Xience V and two for Taxus.

Larger, longer-term trials are required to detect any meaningful safety differences between the two stents, Stone observed. Indeed, stent-thrombosis risk and subsequent death/MI were the key issues identified by the FDA advisory panel in a special hearing last December. Without solid data confirming safety in a significant number of patients, the seemingly superior efficacy of the XIENCE V stent in SPIRIT III may not carry enough weight to win the approval of the panel or the FDA.

And while Boston Scientific's Taxus stent comes out slightly tarnished in SPIRIT III, it's still a win for the company: Boston Scientific has its own version of the Xience V stent, rebranded as the Promus stent, that it acquired through an agreement dating back to the 2006 purchase of Guidant by Boston Scientific and Abbott.

Stone disclosed receiving research support from Abbott and Boston Scientific.