Everolimus-eluting stents reduce both the rate of coronary restenosis and the risk for major cardiac events compared with current paclitaxel-eluting stents, according to an article in the April 23 issue of the Journal of the American Medical Association.

Stents releasing the drugs paclitaxel and sirolimus have been shown to improve long-term event-free survival compared with bare-metal stents. However, restenosis still occurs, and the incidence of stent thrombosis, especially after the first year of implantation, is increased with these drug-releasing stents compared with their bare-metal counterparts, according to background information in the article.

Newer drug-releasing stents are being designed with the goal of enhanced safety, efficacy, or both. Everolimus-releasing stents have shown favorable results in preliminary studies in improving clinical and angiographic outcomes in patients with coronary artery disease.

Gregg W. Stone, MD, of Columbia University Medical Center and the Cardiovascular Research Foundation, New York, and colleagues conducted the SPIRIT III trial to evaluate the everolimus-releasing stent in comparison to the paclitaxel-releasing stent in 1,002 patients with coronary artery disease.

Patients were randomized in a 2-to-1 ratio to receive the everolimus-releasing stent (669 patients) or the paclitaxel-releasing stent (333 patients). Angiographic follow-up was pre-specified at 8 months in 564 patients and completed in 436 patients. Clinical follow-up was performed at 1, 6, 9, and 12 months.

Angiographic in-segment late loss was significantly less with the everolimus-eluting stent compared with the paclitaxel-eluting stent. At 9 months, everolimus stents, compared with paclitaxel stents, were noninferior for the outcome of target vessel failure (47 of 657 patients [7.2 percent] versus 29 of 321 [9.0 percent], respectively).

Use of the everolimus stent compared with the paclitaxel stent resulted in a 44 percent reduction (4.6 percent versus 8.1 percent) at 9 months in the composite of major adverse cardiac events (cardiac death, heart attack, or target vessel revascularization [repeat procedure to unblock a blood vessel]) and a 42 percent reduction in the composite of major adverse cardiac events at 1 year (6.0 percent vs. 10.3 percent). This was due to fewer myocardial infarctions and target lesion revascularization procedures.

"This large-scale, prospective, randomized, single-blind, controlled study demonstrates that an everolimus-eluting stent compared with a widely used paclitaxel-eluting stent results in a significant reduction in angiographic in-segment late loss at 8 months, with noninferior 9-month rates of ischemia-driven target vessel failure," the authors concluded.

In an accompanying editorial, Manesh R. Patel, MD, of Duke University, Durham, N.C., and David R. Holmes, Jr., MD, of Mayo Clinic, Rochester, Minn., wrote that the results of the SPIRIT III trial are promising.

"These data are encouraging and would qualify as demonstrating biological plausibility and mechanistic effect at the level of a phase 2 study," they wrote. "What happens next with the everolimus-eluting stent is critical. The current data from the SPIRIT III trial are analogous to the initial comparisons of drug-eluting vs. bare-metal stents. Restenosis is reduced with the everolimus stent, potentially with a clinical reduction in target lesion revascularization and myocardial infarction. The clinical effect in a broad population of patients who may be clinically exposed following device approval is unknown. Furthermore, clinical efficacy without any mandated angiographic analysis and long-term safety remain important unanswered clinical issues. Postmarketing approval registries, although complex and expensive to perform optimally, may not address both these concerns."

"Physicians must continue to be judicious stewards of the interventional toolbox so that patients continue to allow them the privilege of performing procedures intended to improve their health."