Components of the TAXUS Express² Stent System
On March 4, 2004, the U.S. Food and Drug Administration (FDA) granted approval to the Boston Scientific's Taxus Express² paclitaxel-eluting coronary stent system. The stent has been available since January 2003 in Europe.

The stent system is built on Boston Scientific’s Express² stent, a newer generation device which has been used widely in bare metal stent cases since its introduction in 2002. The Express² has been called highly “deliverable”, meaning that its advanced design allows it to reach distant and difficult lesions in the coronary anatomy more easily. As with all stents, a balloon is advanced, under fluoroscopy, to the narrowing (or lesion) in the coronary artery

To create the Taxus stent, the Express² is coated with a special polymer, a hydrocarbon-based elastomer, called TransLute™, in which the drug paclitaxel (PAK-lih-tacks-el) has been embedded. The polymer is formulated to allow very specific time-release of the drug. (In fact, the clinical trials utilized both a slow-release and a moderate-release version to determine which dosages worked best.)

What is Paclitaxel?
Paclitaxel is a naturally-occurring compound that was found in the bark of the Pacific Yew Tree (Taxus brevifolia) when the National Cancer Institute screened thousands of plant species as possible anti-cancer agents during the 60’s and 70’s. Paclitaxel is the active ingredient in the widely-used chemotherapy drug Taxol™.

cellular microtubules (artist's rendition)

This characteristic is important in striking a crucial balance. While significant accumulation of cells around and inside the stent can clog the interior channel and cause restenosis, some cell accumulation is desirable because allowing a thin layer of endothelial cells to accumulate on the inside of the implanted stent forms a smooth cover, incorporating the device into the artery itself. This process is called endothelialization and is important in preventing the complication of thrombosis (blood cells reacting to a foreign object by clotting and blocking the artery).

electron microscope view of Taxus Express² polymer coated stent

Additionally the proprietary polymer used on the Taxus allows precise control over the dosage and time-release characteristics for paclitaxel, permitting elution of a sufficient amount of the medication to inhibit cell accumulation around the stent and prevent restenosis, yet still allow a thin cover to form. Importantly this low and very localized dosage does not impact the patient adversely the way that a high dosage systemic course of chemotherapy would.

Clinical Trial Results
In order to test the three-way combination of the Express² stent, the time-release polymer coating and the anti-inflammatory drug paclitaxel, a series of clinical trials were initiated to measure the safety and effectiveness of the system. The trials compared patients who received the Taxus stent with those who received the Express² bare metal stent; the trials were double-blinded -- neither the physicians nor patients knew which stent they had. The TAXUS-IV nine-month results were reported at the TCT meeting in September 2003 and are summarized as follows:

• Over 1300 patients in 73 centers took part
• Combined MACE (Major Adverse Cardiac Events – repeat intervention with angioplasty or surgery, heart attack, death) was reduced from 15% in the control group to 8.5% in the Taxus group – a reduction of 43%
• In-stent restenosis (where a blockage recurred inside the stent) went from 24.4% down to 5.5% -- a 77% reduction
• Diabetics, a subgroup typically at high risk for restenosis, experienced even higher rates of restenosis reduction, with those on insulin going from 42.9% to 7.7% and those on oral meds from 29.7% to 5.8% -- approximately 22% of those studied were diabetics
• TLR (Target Lesion Revascularization – whether a specific blockage that was stented needed to be reopened, either through angioplasty or surgery) went from 11.3% down to 3% -- a 73% reduction
• TVR (Target Vessel Revascularization – whether a blockage anywhere in the target artery needed to be reopened) went from 12% to 4.7% -- a 61% reduction (this was the primary endpoint of the trial because it measures the total effect of implanting a stent in the artery)
• Stent thrombosis (clotting) was similarly low (less than 1%) for both Taxus and control groups

Complete results of the study can be found here, but the benefits of the Taxus drug-eluting stent are quite apparent. The FDA has asked Boston Scientific to continue its tracking of patients who receive the Taxus in a study that will enroll 2,000 patients.

More information on the Taxus stent can be found at the manufacturer's web site www.taxus-stent.com.