Late-Breaking Trials from the European Society of Cardiology Congress

Source: Stone GW, Ellis S. Presented September 15, 2003, at the annual Transcatheter Cardiovascular Therapeutics Symposium in Washington, DC.

Drs. Gregg Stone and Stephen Ellis presented the 9-month clinical and angiographic results from TAXUS IV, which was designed to assess the safety and efficacy of the TAXUS™ slow-release polymer-based paclitaxel-eluting Express2 stent (Boston Scientific) in a broad cross-section of patients. This study randomized 1326 patients to receive the TAXUS™ stent or the bare metal Express2 stent. Lesions were single, de novo, between 10-28 mm in length, in vessels > 2.5 mm, and less than 3.75 mm in diameter. All patients received prerandomization ASA 325 mg, and clopidogrel 300 mg was recommended. Patients were stratified by presence of diabetes and vessel diameter prior to randomization. All patients received clopidogrel 75 mg daily for 6 months after procedure. Clinical follow-up was obtained at 1, 4, and 9 months and is planned yearly for 5 years. The primary end point was ischemia-driven target vessel revascularization (TVR) at 9 months.

A total of 662 patients underwent TAXUS™ stent implantation, and 652 received control stents. There were no significant differences between the groups with regard to baseline clinical features. A total of 23.4% of TAXUS™ patients and 25% of control patients were diabetic (P = .52). There were no differences between the groups with regard to baseline angiographic or procedural characteristics. GP IIb-IIIa inhibitors were used in 57.7% of TAXUS™ patients and 56.7% of controls (P = NS). Acute angiographic results were equivalent between the 2 groups. At 30 days, there were no differences between the groups with regard to MACE or any of its individual components (cardiac death, MI, target lesion revascularization (TLR), or TVR. At 9 months, TVR was reduced by 61% in the TAXUS™ group (4.7% vs 12.0%; P < .0001) and TLR was reduced by 73% (3.0% vs 11.3%; P < .0001). Nine-month MACE was significantly lower in the TAXUS™ group (8.5% vs 15.0%; P = .0002), driven by the need for repeat revascularization, as there were no differences in the rates of cardiac death or MI. Subgroup analysis demonstrated significant reductions in restenosis among LAD vs non-LAD location, diabetics (particularly those receiving insulin), in small vessels (< 3.0 mm), and in long lesion subsets. Stent thrombosis rates were low, with 4 (0.6%) in the TAXUS™ group and 5 (0.8%) in the control group.

Angiographic follow-up obtained in 559 patients demonstrated lower rates of binary angiographic restenosis (>50% diameter stenosis) and lower rate loss in the patients receiving the TAXUS™ stent. In conclusion, TAXUS IV demonstrates that the paclitaxel-eluting TAXUS™ stent is safe and highly effective in reducing clinical and angiographic restenosis in a clinically relevant population of patients undergoing coronary stent implantation.

Comment by Sarah M. Vernon, MD

To say that the results of TAXUS IV have been highly anticipated would be an understatement. Interventional cardiologists in the United States have been quick to embrace the Cypher sirolimus-eluting Bx-VELOCITY stent (Johnson & Johnson) based primarily on the results of the SIRIUS study. However, enthusiasm has been tempered somewhat by inconsistent availability, some limitations in stent flexibility and deliverability, and by early reports suggesting that stent thrombosis rates have been higher in clinical practice than were reported in clinical trials. An embargo leak prior to the presentation of TAXUS IV resulted in a drop in stock price of Johnson & Johnson, the makers of the only drug-eluting coronary stent currently FDA approved. Boston Scientific initially filed data with the FDA in June 2003, and the results of TAXUS IV are scheduled to be reviewed by the FDA on November 20, 2003, which the company hopes would put the TAXUS™ stent on track for approval late in 2003.

What TAXUS IV does not tell us is how this stent will perform in comparison to the Cypher sirolimus-eluting stent currently in clinical use. Data addressing this question may, or may not, become available in the future. The start of the 1200-patient REALITY trial comparing the Cypher and TAXUS™ stents head-to-head has been delayed and may not go forward as planned.

Dr. Vernon, Assistant Professor of Medicine Director, VAMC Cardiac Catheterization Laboratory, University of New Mexico Health Sciences Center, Albuquerque, NM, is on the Editorial Board of Clinical Cardiology Alert.