BARCELONA, Spain -- In a head-to-head trial, the investigational drug-eluting stent, Xience, which is coated with everolimus, significantly outperformed Taxus, the popular paclitaxel-eluting device.
BARCELONA, Spain, Sept 5 -- An investigational drug-eluting stent called Xience, which is coated with everolimus, significantly outperformed Taxus, the popular paclitaxel-eluting device, researchers said here today.
The report emerged, however, as investigators were re-evaluating the entire field of drug-eluting stents in view of two ominous meta-analyses that were reported here Sunday.
After six months, the Xience stent had a late loss of 0.11 mm compared with a 0.16 mm late loss for patients treated with Taxus (P<0.0001), said Patrick Serruys, M.D., Ph.D., of Erasmus University in Rotterdam, The Netherlands. Taxus is one of the two drug coated stents approved by the FDA.
Dr. Serruys was principal investigator of SPIRIT-II, a phase II trial designed as a non-inferiority trial. But the results demonstrated that Xience was "even superior to Taxus," Dr. Serruys reported at the European Society of Cardiology/World Congress of Cardiology meeting.
The SPIRIT-II trial enrolled 300 patients, mean age 60, who had de novo lesions of less than 28 mm long in vessels at least 2.5 mm in diameter up to 4.25 mm in diameter. Two hundred and twenty-three patients received Xience stents and 77 had Taxus stents implanted.
The study was powered to show non-inferiority if both stents had a late loss of 0.16 mm.
Neointimal volume and percent volume reduction, both markers of the efficacy of the stent at preventing restenosis, were also significantly better with Xience. Neointimal volume was 3.8% versus 14.4%, for a 73% relative reduction (P<0.0001), Dr. Serruys said. Percent volume reduction was 2.5% versus 7.4%, for a relative reduction of 66% (P<0.001).
Despite these numbers, there were only restrained congratulations because drug-eluting stents have come under a cloud since Sunday, when results of two meta-analyses suggested that the devices are associated with an increased risk of in-stent thrombosis and increased all-cause mortality.
For example, Robert Harrington, M.D., of Duke in Durham, N.C., spent the bulk of his five-minute discussant presentation suggesting that it is time to go slowly with new drug-eluting stents and to carefully evaluate long term outcomes of the estimated six million such devices already implanted worldwide.
"In days of balloon angioplasty, we worried about thrombus formation for 12 to 24 hours, and when bare metal stents were introduced, we worried for seven to 14 days," Dr. Harrington said.
The worry with drug-eluting stents may "be extended to years," he said.
In one of two meta-analyses reported Sunday, patients treated with Cypher, a sirolimus-eluting stent, had significantly greater mortality and non-fatal myocardial infarctions at three years than did similar patients who were treated with bare-metal stents.
During a press briefing, Dr. Serruys said even he is not sure whether the significantly better late loss numbers posted by Xience were an advantage or a red flag.
"It is clear we have to find the right balance," Dr. Serruys said. He noted that it is difficult to find fault with a drug that is so effective at stopping neointimal hyperplasia, but since everolimus is "mechanistically similar to sirolimus" he acknowledged that there could be problems down the road. Yet he cautioned that "it is too early to make a statement."
Everolimus belongs to the same class as sirolimus, and both drugs target mTOR. Some drug-eluting stent critics have suggested that limus drugs are such powerful blockers of cell proliferation that they also block the re-endothelialization of the stent struts, thus exposing a bare -- and potentially prothrombotic -- surface to blood flow. That isn't a problem as long as patients are maintained on dual antiplatelet therapy with aspirin and Plavix (clopidogrel), but when antiplatelet treatment stops it may cause problems.
Currently, guidelines recommend that dual antiplatelet therapy be continued for three months for patients treated with Cypher stents and six months for those who receive Taxus stents.
But Sidney Smith Jr., M.D., of the University of North Carolina at Chapel Hill, and chairman of the American College of Cardiology/American Heart Association Percutaneous Coronary Intervention Guideline Committee, pointed out that the guidelines also recommend that dual antiplatelet therapy be continued for a year in patients who have no excess bleeding risk.
All stented patients should take aspirin for life, Dr. Smith said, but he said there is no evidence that extending the dual antiplatelet therapy beyond a year will reduce the late thrombosis risk.
In fact, there were two reports of in-stent thrombosis in the SPIRIT-II -- one in the Xience arm at 53 days in a patient who was on a dual antiplatelet regimen, and a fatal event in the Taxus arm at 50 days in a patient who was also maintained on the dual regimen.
Elliott M. Antman, M.D., of Harvard Medical School, and a spokesperson for the AHA, said the SPIRIT-II results are clearly impressive, but he, too, cautioned about the need to confirm the benefit -- both efficacy and safety -- with larger trials and longer term results.
The Xience stent is being developed by Abbott Laboratories, which sponsored the trial.