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Reigning Coronary DES King Matches Its Predecessor

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Everolimus Stent Reduces Stent Thrombosis

RESET is the largest study to compare everolimus- and sirolimus-eluting coronary stents. This study is important because the sirolimus-eluting stent has been the standard coronary stent for both safety and efficacy.

The two stents differ in several key ways. The struts of the everolimus-eluting stent (EES) are thinner, it carries a lower polymer load and a more durable polymer, and it contains a lower dose of the drug, which is already less potent than sirolimus.


Dr. Stephan Windecker

Adding the RESET results to seven earlier comparisons of these two stents, a total population of more than 11,000 patients, showed that the rate of target lesion revascularization in patients who received EES was a relative 13% lower than in patients who received sirolimus-eluting stents (SES), a strong but statistically nonsignificant trend in favor of the EES.

When my associates and I combined the RESET data on the rate of definite stent thrombosis with results from three earlier comparisons, we found that the EES produced a statistically significant, 49% relative reduction in this safety end point. We now know for the first time that EES produce a significant risk reduction for this measure. I believe that this difference in stent thrombosis was not seen in the RESET data alone because of the extremely low thrombosis rates in both arms of the study, and because follow-up only extended for 1 year. Prior results showed that the EES have an especially low rate of very late stent thrombosis, once they have been in place for more than 1 year.

The RESET results show that EES are at least as effective as SES, and EES have the added value of being more deliverable, with a higher procedural success rate. Also important, EES have a good efficacy profile despite a lower drug concentration than DES and lower pharmacologic potency. As for safety, in RESET, EES showed no difference in the risk for death, cardiac death, or myocardial infarction compared with SES.

Stephan Windecker, M.D., is head of interventional cardiology at the Swiss Cardiovascular Center in Bern. He said that his institution has received research grants from Abbott, Biosensors, Biotronik, Boston Scientific, Cordis, and Medtronic. Dr. Windecker made these comments as an invited discussant at the meeting.


 

FROM THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY

PARIS – The current master of the coronary drug-eluting stent universe, the everolimus-eluting stent, finally proved itself fully worthy of its position, matching the efficacy and safety performance of its predecessor, the sirolimus-eluting coronary stent.

"The sirolimus-eluting stent was the most widely used and extensively studied first-generation drug-eluting stent. The clinical outcomes of the sirolimus-eluting stent should be regarded as the benchmark for current and future second-generation drug-eluting stents," Dr. Takeshi Kimura said at the annual congress of the European Society of Cardiology. "In this large-scale, randomized, controlled trial comparing EES [everolimus-eluting stents] with SES [sirolimus-eluting stents], EES was demonstrated to be noninferior to SES with respect to target-lesion revascularization rate at 1 year and angiographic in-segment late loss at 8-12 months," said Dr. Kimura, professor of cardiovascular medicine at Kyoto (Japan) University.

"This study is important, because the sirolimus-eluting stent has been the standard of care. We have good, long-term results with the SES, and almost all we know about drug-eluting stents is from the SES," said Dr. Uwe Zeymer, an interventional cardiologist and professor at the Institute for MI Research in Ludwigshafen, Germany. Now that interventional cardiologists have broadly adopted EES as their primary tool in percutaneous coronary interventions, "it’s important to show they are as good and as safe as SES," he said in an interview. EES have largely replaced SES because they are easier to deliver into coronary arteries. "Now we can also say that EES equal the standard of care" for drug-eluting stents, the DES, for efficacy and safety. "It is reassuring."

The Randomized Evaluation of Sirolimus-Eluting versus Everolimus-Eluting Stent Trial (RESET) randomized 3,197 all-comer patients at 100 Japanese centers during February-June 2010. The patients had, on average, 1.2 coronary lesions each that required stenting, and each patient received an average of 1.5 stents.

After 12 months, the study’s primary clinical end point, need for target lesion revascularization, occurred in 4.3% of patients treated with EES and in 5.0% of those treated with SES, a difference that was not significantly different and that met the study’s prespecified criterion for noninferiority, Dr. Kimura reported.

Other safety and efficacy measures included the 1-year rate of all-cause death, myocardial infarction, stent thrombosis, and the rate after 8-12 months of in-segment and in-stent late loss. Patients who received EES and DES showed no statistically significant differences for any of these measures, and the rate of in-segment late loss also fell within the study’s prespecified criterion for noninferiority.

Longer-term follow-up is needed to see whether EES could reduce the rate of late adverse events, such as late restenosis or stent thrombosis, that occur more than 1 year after stent placement," Dr. Kimura said.

Dr. Kimura said that he has served on the scientific advisory board and has received honoraria from Abbott Vascular, Cordis Cardiology, and Terumo. Dr. Zeymer said that the Institute of MI Research in Germany, where he works, has received research grant support from multiple cardiac device companies.

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