WASHINGTON — The everolimus-eluting stent Xience V produced a clinically significant 43% reduction in major adverse cardiac events, compared with the paclitaxel-eluting Taxus at 1 year, Dr. Gregg W. Stone reported at the annual Transcatheter Cardiovascular Therapeutics conference, sponsored by the Cardiovascular Research Foundation.
That major secondary end point finding comes from Abbott Laboratory's 5-year SPIRIT III trial of 1002 patients randomized 2:1 to receive either the Xience V or the Taxus stents. This is the first time a drug-eluting stent system has shown a statistically significant improvement in event-free survival, compared with another FDA-approved drug-eluting stent in a pivotal randomized clinical trial, noted Dr. Stone of Columbia University and director of the Cardiovascular Research Foundation, New York.
The Xience V has been licensed in Europe and parts of Asia since 2006, and currently awaits approval from the Food and Drug Administration. Abbott anticipates its licensure in the first half of 2008, a company statement said.
Earlier this year at the American College of Cardiology meeting, Dr. Stone presented data showing that Xience produced a statistically significant reduction of 50%, compared with Taxus, in in-segment late loss, the primary end point of the SPIRIT III. Now, at 1 year, rates of target vessel failure (TVF) (cardiac death, MI, or ischemia-driven target vessel revascularization) were 8.3% with Xience versus 10.8% for Taxus, a 25% difference representing a nonsignificant trend in that major secondary end point.
However, the 43% difference between the two stents in major adverse cardiac events (MACE)—5.8% for Xience vs. 9.9% with Taxus—was highly significant, and, Dr. Stone believes, is more important than TVF in terms of analyzing the performance of the two stents. While the TVF includes factors such as side vessel branches and discordant lesions, the MACE outcome “is much more specific to stenting itself.”
There were no differences in cardiac death (0.8% for Xience and 0.9% for Taxus) at 1 year, and MI rates—2.6% for Xience, 3.7% for Taxus—did not differ significantly. Ischemia-driven target lesion revascularization accounted for the majority of the MACE difference, with rates of 3.3% with Xience and 5.6% with Taxus, a “strong trend” difference of 41%. The 5.6% for Taxus “is a good number, but Xience was better,” remarked Dr. Stone, who is a consultant for both Abbott Vascular and Taxus manufacturer Boston Scientific.
Thrombosis rates at 1 year were low in both groups, 0.8% for Xience and 0.6% for Taxus. No differences in thrombosis rates were seen when the figures were broken down according to those occurring at 30 days or sooner versus beyond 30 days.
Subgroup analyses of the 8-month late loss were consistent across most parameters, including the angiographic cohort of 501 patients, gender, single or dual vessel treated, and lesion length. One exception was by age, with the greatest reduction occurring in late loss among those aged at least 63 years, compared with those younger. “This was a significant difference. I don't know why,” Dr. Stone commented.
Another somewhat surprising subgroup finding was that the Xience worked better in nondiabetics than in the diabetic population, the opposite of what has been seen in previous studies. There were, however, only 280 diabetics in SPIRIT III. “Again, you have to be cautious with subgroups,” he remarked, “because the study wasn't powered to show those differences.”
Indeed, the ongoing SPIRIT IV trial is designed to examine that issue. The single-blind, randomized, multicenter study will enroll 3,900 patients for the treatment of up to three de novo native coronary lesions. The primary end point is TVF at 270 days, and, like SPIRIT III, patients will be followed out to 5 years. “We'll be looking at subgroups,” Dr. Stone said.