CYPHER
The Cypher drug eluting stent manufactured by Cordis, a Johnson and Johnson company, utilized the drug Sirolimus to combat restenosis. The Cypher stent comes in a variety of lengths and diameters. These range from 8 to 33 mm in length and 2.5 to 3.5 mm in diameter. These coronary stents are constructed out of 316L stainless steel (low-magnetic, low-carbon) and are coated with a mixture of two polymers, parylene C, and the Sirolimus drug. The two non-erodible polymers (polyethylene-co-vinyl acetate (PEVA) and poly n-butyl methacrylate (PBMA)) are combined in a 67/33 percent ratio respectively and then applied to a parylene C coated stent. A drug free coat of PBMA is also applied to the stent surface to control drug release. [3]
Stent delivery is performed using one of two methods, the RaptorRail rapid delivery system with a useable length of 137 centimeters, or the Over-the-Wire delivery system with a useable length of 145 centimeters. Both systems use a single-layer nylon balloon approximately 2mm longer than the stent itself. Nominal pressure is rated at 11atm while burst pressure is approximately 16atm.
[3]
Two large clinical trials have been performed to determine the safety and efficacy of the Sirolimus-eluting Cypher stent when compared to a control, uncoated BX Velocity 316L stainless steel stent. These studies were RAVEL conducted in 2001, and SIRIUS in 2003. [3]
- RAVEL was a randomized, double blind supportive study involving 238 patients (120 Cypher, 118 control) with a pre-specified end point of in-stent late loss at 6 months. The results of RAVEL were promising – in-stent late loss for the Cypher stent was at -.01mm while versus the control at .80mm. Also, at 720 days, 96.6% of Cypher stents remained MACE free compared to 80.4% in the control group (a difference of 9.5%).
- SIRIUS was a pivotal study in determining the safety and effectiveness of the Cypher stent in reducing target vessel failure compared to the control stent. It involved 1,058 patients (533 Cypher, 525 control) in a randomized, double blind study. The results of SIRIUS were a significantly lowered rate of TVF at 9 months when compared to the control. At 9 months, TVF for the Cypher stent was at 8.8% whereas for the control, 21% (% difference of 12.1%). Also, at 360 days, 91.7% of Cypher patients remained MACE free compared to 77.4% for the control group (% difference of 11.8%)
Based on the two clinical studies, the FDA decided to approve the Sirolimus-eluting Cypher stent on April 24th , 2003 . In less than one month, the Cypher stent had been implanted in 19,843 patients compared to only 1,444 the month before (tracked by Solucient). At an initial cost of approximately $3,200, or about three times the price of a regular, uncoated stent, the profit for Johnson and Johnson after royalties and licensing is estimated to be $1,750/stent. In less than one year after Cypher won government approval, one in every 1,500 Americans was wearing a Cypher stent. According to Solucient, between 2002 and 2003, Cypher helped to contribute to a 15% decline in the number of coronary artery bypass grafts performed, as well as a 31% decrease in the use of bare metal uncoated stents. [1, 2]
TAXUS
Following up on the success of the Sirolimus-eluting Cypher stent manufactured by Cordis, Scientific designed their own drug-eluting stent in hopes of creating some competition in the drug-eluting stent in hope of taking some of Cordis's monopoly. The Boston Scientific stent, called Taxus, utilizes the drug Paclitaxel. Paclitaxel is in a class of drugs called taxanes. Its main uses are to prevent the growth of cancer cells in the body, treat metastatic breast cancer, metastatic ovarian cancer, and Kaposi's Sarcoma. [5, 6]
Paclitaxel works by promoting the assembly of microtubules and stabilizes them by preventing depolymerization. This stability results in an inhibition of the reorganization of the microtubule network during the cell mitotic process – thus preventing the accumulation of anti-inflammatory cells at the site of the injury. [5]
The Taxus stent comes in lengths of eight to 28 mm and diameters of 2.5 to 3.75mm. The stent is constructed out of 316L stainless steel and is coated with the Translute polymer [ poly(styrene-b-isobutylene-b-styrene)]. This polymer functions similarly to the PEVA/PBMA copolymer used in the CYPHER stent. This polymer is also notable for its excellent vascular compatibility, which is extremely important in a system designed for long-term implementation. The pharmacokinetics of the paclitaxel release are slightly different from the CYPHER stent: Burst release in the first 48 hours, slow release over the next 10 days, and 
no further release after 30 days.
Another point of interest concerning the Paclitaxel and Translute polymer mix is that Boston Scientific was not the first to manufacture a coated stent using Paclitaxel. An earlier stent created by Guidant/Cook also used the drug Paclitaxel but not encapsulated in a polymer. The Translute polymer has the very important role of binding to the drug and allowing for a time-controlled release of the drug. Guidant/Cook's stent was simply dipped into the drug – this created speculation that the drug was being lost even before the insertion of the stent due to the burst effect. [7]
Taxus stent delivery was performed using one of two systems, the Monorail stent delivery system with a delivery system working length of 140cm or the Over-the-Wire stent delivery system with a delivery system working length of 135cm. Both use a balloon with a rated nominal pressure of 9atm and a rated burst pressure of 18atm. [4]
Multiple clinical trials were performed using the Taxus drug-eluting stent to determine their efficacy compared to plain bare metal stents. Several of the more important trials are highlighted below. TAXUS I was begun in 2002. [4]
- Taxus I was a randomized, double blind study comparing the slow-rate release Taxus stent to a bare metal control stent. 61 patients were involved (31 Taxus, 30 control) in the study with the primary endpoint of MACE at 30 days. There was no significant effect of Taxus on MACE at the end of 30 days, as both Taxus and the control had 0% occurrence. At 180 days however, the Taxus still showed 0% MACE while the control showed 7%. At 365 days, Taxus showed 3% and the control 10%. The conclusion inferred from this initial supportive study was that the Taxus stent was superior to the bare metal stent in reducing the rate of MACE.
- Taxus II was a prospective, double blind study involving 267 patients (131 Taxus, 136 control) to demonstrate the safety and efficacy of the Paclitaxel eluting stent versus the control bare metal stent. The endpoint was predetermined to be MACE at 6 months. Results showed that the Taxus stent showed only 8.5% MACE compared to 19.5% with the control, a % difference of 11.1. MACE at 12 months for Taxus was 10.9% compared to 22.0% for the control (% difference of 11.1). The conclusion was that the Taxus stent effectively reduced the processes that lead to MACE and restenosis.
- Taxus IV was designed to demonstrate the superiority of the Taxus stent in preventing TVR at 9 months when compared to the control bare metal stent. 1,326 patients were involved (662 Taxus, 652 control) with a month target vessel revascularization endpoint. The results showed TVR of 4.7% in Taxus compared to 12.0% control and TLR in Taxus of 3.0%, 11.3% in control. The conclusion was that the Taxus stent significantly reduced 9 month TVR when compared to bare metal stents.
The clinical studies showed the effectiveness of the Taxus stent, and Boston Scientific won government approval for their stent on March 6th , 2004 . Being extremely new, demographics for the Taxus stent are not as publicized, but in their 2003 financial report, Boston Scientific claimed market leadership overseas in the drug-eluting stent market with sales of $200 million. Between March 8th and March 19th , Boston Scientific had garnered $42 million in the United States . 92,000 units had been shipped in those 10 selling days. On the 31 st of March, sales of the Taxus stent produced $98 million in the U.S. The stents are currently marketed for $2,600/stent, competitively priced with the Cypher stents manufactured by Johnson and Johnson. [5]