A recent study published in JAMA found that drug-releasing stents improve outcomes for patients with coronary artery disease who received angioplasty to open narrowed arteries. Gregg W. Stone, M.D. (Columbia University Medical Center and the Cardiovascular Research Foundation, New York) and colleagues showed that compared to the often-used paclitaxel-releasing stents, stents that release the drug everolimus lowered the rate of renarrowing of arteries and significantly lowered the risk of major cardiac events.
It has been previously shown that compared to bare-metal stents, paclitaxel- and sirolimus-releasing stents result in improved long-term event-free survival. The benefits of drug-releasing stents, however, are tempered by restenosis – a condition characterized by the renarrowing of coronary arteries after angioplasty. In addition, drug-releasing stents are more likely to result in clots in blood vessels (stent thrombosis) after the first year of implantation compared to bare-metal stents. Researchers and developers are currently designing new drug-releasing stents that are safer and more effective. In earlier studies of clinical and angiographic (i.e. using radiology to view blood vessels) outcomes among patients with coronary artery disease, stents releasing the drug everolimus have presented favorable results.
To compare everolimus-releasing stents with paclitaxel-releasing stent, Stone and colleagues conducted the SPIRIT III trial using a sample of 1,002 patients with coronary artery disease. During randomization, 669 patients received the everolimus-releasing stent and 333 received the paclitaxel-releasing stent. After 8 months, 436 of 564 patients who were scheduled for an angiographic follow-up completed it, and clinical follow-ups occurred after 1, 6, 9, and 12 months.
Results showed that restenosis as measured by angiography was significantly lowered in the group receiving the everolimus-releasing stent compared to the paclitaxel group. After 9 months, 7.2% of patients receiving everolimus stents compared to 9.0% receiving paclitaxel stents demonstrated target vessel failure. The risk of major adverse cardiac events (cardiac death, heart attack, or target vessel revascularization) at nine months was reduced by 44% in patients receiving the everolimus stent compared with the paclitaxel stent. After 1 year, this reduction in risk was 42%, and it can be explained by fewer heart attacks and target lesion revascularization procedures for patients receiving everolimus.
The researchers conclude that, “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.”
Manesh R. Patel, M.D. (Duke University, Durham, N.C.) and David R. Holmes, Jr., M.D. (Mayo Clinic, Rochester, Minn.), in an accompanying editorial, believe that the results found by Stone and colleagues are optimistic.
“These data are encouraging and would qualify as demonstrating biological plausibility and mechanistic effect at the level of a phase 2 study,” they write. “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 [heart attack]. 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,” they conclude.
Comparison of an Everolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients With Coronary Artery Disease: A Randomized Trial
Gregg W. Stone; Mark Midei; William Newman; Mark Sanz; James B. Hermiller; Jerome Williams; Naim Farhat; Kenneth W. Mahaffey; Donald E. Cutlip; Peter J. Fitzgerald; Poornima Sood; Xiaolu Su; Alexandra J. Lansky; for the SPIRIT III Investigators
JAMA (2008). 299[16]: 1903-1913.
Written by: Peter M Crosta