[TCT2007]Next-generation DES Targeting More Complex Lesions

Clinical efficacy and safety of second-generation DES appear equivalent in trials to date.

T he efficacy and safety of second-generation DES appear to be similar to first-generation devices in clinical trial results to date. Next-generation stents, such as lesion-specific DES, hold promise for addressing more complex lesions, but they must first undergo more longterm examination, said Eberhard Grube, MD.

Grube, of HELIOS Klinikum Siegburg, Germany, reviewed clinical trial results for the second-generation DES models Endeavor (Medtronic) and Xience V (Abbott), which are expected to reach the U.S. market in 2008, and looked ahead to the promise of other stent models now available inEurope or in development. He said the first generation of DES- Cypher (Cordis, Johnson & Johnson) and Taxus (Boston Scientific) - are themost thoroughly studied, and the second-generation models that have been introduced are “mostly without a profound database” of experience. After early safety and efficacy studies, longterm safety trials in large patient populations are needed to assess performance differences among devices, he said.

The first-generation stents now have clinical experience extending up to 5 years with near-complete followup in trials that include approximately 3,500 and 1,800 patients for Taxus and Cypher, respectively. Clinical trial experience with the second-generation Endeavor zotarolimus-eluting stent is up to 2 years with near-complete follow-up in approximately 1,700 patients, and clinical experience with the Xience V everolimus-eluting stent is up to 1 year with near-complete follow-up in approximately 1,300 patients.

Adequately powered, long-term studies will be needed to confirm the equivalence or superiority of these newer devices, he said.

Late lumen loss

Grube reviewed some of the safety and efficacy findings in first- and secondgeneration DES in clinical trials to date. DES efficacy requires the prevention of intimal hyperplasia, he said. The best angiographic surrogate for hyperplasia is late lumen loss, but the surrogate that matters most to the patient is TLR.

The clinician should keep this in mind when evaluating clinical trial results, Grube said. In the pivotal SIRIUS and TAXUS IV trials of Cypher and Taxus, respectively, TLR rates at 3 years were similar, despite significant differences in late lumen loss favoring Cypher.

In the ENDEAVOR IV trial, which compared Endeavor with Taxus, the second-generation device demonstrated noninferiority in the primary efficacy endpoint of target vessel failure at 9 months, Grube said. (See related article on ENDEAVOR IV 1-year results, which were announced at TCT 2007.)

In a broad review of 29 clinical trials comparing Taxus and Cypher, there was no difference in target lesion revascularization between the two devices, Grube said (Figure).

The study, by Kereiakes, is to be published this month in the Journal of the American College of Cardiology.

Regarding safety, Grube recalled the alarm raised at the European Society of Cardiology meeting in 2006, when a meta-analysis by Edoardo Camenzind suggested an increase in Qwave MI with Cypher vs. Taxus.
“That, as we all know, has proven not to be the case,” Grube said.

He noted also that different definitions of stent thrombosis can make it difficult to compare results between trials.
Grube urged operators, if they are concerned about long-term results with DES, to “go back to the early days,” and employ the stents carefully.“Technique does matter,” he said.

The future

Grube also reviewed some of the stent technologies still in development, such as bioabsorbable polymers, controlled application of polymers, and nonpolymer-based devices.

In addition, he said, lesion-dedicated DES are in development to address the needs of complex types of occlusions. These include the Devax stent, for use in bifurcations, and the Xtent system offering customized length with interdigitized stent segments.