ACC: Stent Eluting Two Drugs Offers No Extra Benefit Over One

NEW ORLEANS, March 27 -- The first trial of a stent coated with two drugs -- estradiol and rapamycin -- showed no benefit over a stent eluting rapamycin alone.

Used for more than 500 coronary patients, the double-drug coating on the investigational ISAR stent did not reduce late- lumen loss or any other outcomes compared with the single-drug coating, said Julinda Mehilli, M.D., of Deutsches Herzzentrum of Technische Universtitt in Munich, Germany.

The ISAR stent has a rough surface believed to be capable of carrying more drugs, making it a good candidate for a dual-drug strategy.

Adding estradiol, a hormone previously shown to promote endothelial recovery, had been expected to improve the relatively high late-thrombosis rate seen with rapamycin-coated stents, she said at the American College of Cardiology meeting.

Despite the negative findings she presented here at the American College of Cardiology meeting and published simultaneously in the March 27 issue of the Journal of the American College of Cardiology, some clinicians remained optimistic about the double-drug strategy.

More such combinations can be expected, said William Knopf, M.D., of Saint Joseph's Hospital in Atlanta, who moderated a press conference during which the results were discussed.

"Although being a negative study, it is certainly the future of drug eluting stent technology to try and find combinations of drugs that reduce inflammation and reduce the potential effects of delayed healing and subacute thrombosis or late thrombosis," he said.

The study randomized 502 patients with stable or unstable angina or a positive stress test to receive a polymer-free 17-beta-estradiol plus rapamycin coated stent or a polymer-free rapamycin coated stent. Both drugs were in 1% concentration.

The groups had similar baseline and treatment characteristics. Nearly all patients received beta-blockers, angiotensin-converting enzyme inhibitors, and statins. Duration of clopidogrel (Plavix) after percutaneous coronary intervention was similar as well. Stent placement was successful for 99.6% of the double-drug stent group patients and 100% of the single-drug stent group.

At one-year clinical and about six-month angiographic follow-up, none of the findings showed even a trend toward superiority for the double-drug stent. The researchers reported (double- versus single-drug stent):

• 0.520.58 mm versus 0.510.58 mm late lumen loss (P=0.83),
• 17.6% versus 16.9% binary restenosis of at least 50% on angiography (P=0.85),
• 14.3% versus 13.2% target lesion restenosis (P=0.72),
• 7.9% versus 8.0% combined incidence of death or myocardial infarction (P=0.98, 2.0% versus 2.4% death), and
• 0.8% versus 1.2% 12-month stent thrombosis (P=0.99), with an additional three cases of possible stent thrombosis in each group and no probable stent thrombosis cases.

Although there were no significant differences between the groups, "both groups in the present study showed late lumen loss measures greater than those observed for polymer-based sirolimus-eluting stents but lower than the in-stent late lumen loss of 0.61 mm observed for phosphorylcholine polymer-based zotarolimus-eluting stents," they wrote in the paper.

"On the other hand, the in-stent late lumen loss of 0.52 mm in the ERES group of our study is similar to the 0.54 mm value of this index in the estradiol group of the EASTER trial and much lower than the 0.82 and 0.86 mm values reported recently for moderate- and fast-release estradiol-eluting stents," they continued.

Dr. Mehilli cautioned that the study was powered only to look at late lumen loss, and it, like other drug-eluting stent device trials, was too small and too short to draw conclusions on stent thrombosis in clinical settings.

Furthermore, she noted that the study lacked intravascular ultrasound (IVUS), angioscopy and optical coherence tomography to see if endothelial coverage of the stents differed between groups.

Dr. Mehilli speculated that estradiol might not have showed an additional effect because it was overshadowed by the powerful inhibitory effect of rapamycin.