Drug-Eluting Stent Safety Issues Dominate TCT Meeting

More than 11,000 interventional physicians attended the annual Transcatheter Cardiovascular Therapeutics (TCT) conference, held late last month in Washington, DC. The meeting featured interactive cardiac catheterization demonstrations, hands-on 3-D workstations for computed tomography imaging, one-on-one specialty device training, displays and demonstrations of the latest advances in cardiovascular and related technologies from 160 medtech manufacturers, and hundreds of case studies. Despite such an array of features, however, discussions surrounding the safety of drug-eluting stents dominated the six-day event.

In September, clinical presentations at the 2006 World Congress of Cardiology, in Barcelona, Spain, cast a pall over the interventional cardiology sector by suggesting that there is a significant risk of late-term thrombosis associated with the use of drug-eluting stents in coronary angioplasty. With those somber presentations freshly in mind, it's understandable why many cardiologists, medtech manufacturers, and industry analysts expressed relief that the studies presented at TCT generally showed no increased risk of thrombosis and resulting myocardial infarction or death with drug-eluting stents when compared with bare-metal stents.

Yet, the issue of drug-eluting stent safety is far from resolved, as clinicians and researchers point to different criteria and different patient groups that have been used to define stent thrombosis in many of the studies presented to date.

During TCT, a new definition for stent thrombosis was presented. Designed to eliminate the variability of criteria used in clinical trials of drug-eluting stents, the definition was developed by the Academic Research Consortium (ARC), whose members include academic institutions, clinical centers, stent manufacturers, and FDA. To date, variability among definitions has made it difficult to compare the true rates of late stent thrombosis across trials.

The proposed ARC definition includes patients with confirmed stent thrombosis, probable stent thrombosis, and possible stent thrombosis. FDA has asked stent manufacturers to use this model when they report their clinical data on stent safety at an agency-sponsored meeting set for early December in Washington, DC.

"The definitions developed by ARC are important because they seek to standardize how we view an event like thrombosis across all clinical studies," said TCT presenter Patrick Serruys, MD, PhD, chief interventional cardiologist at the Thorax Center of Erasmus University (Rotterdam, Netherlands) and ARC coleader. "Without a common language, ambiguity arises, and that is not helpful for physicians or the patients they treat. With these standardized definitions, we succeed in creating a foundation for clinical advancement of interventional cardiology."

Another TCT highlight was the presentation of drug-eluting stent data from studies conducted through the Cardiovascular Research Foundation, which sponsors the TCT meeting. The studies—metaanalyses of existing data from independent trials—compared bare-metal stents with the only drug-eluting stents approved by FDA: Taxus, manufactured by Boston Scientific Corp. (Natick, MA), and Cypher, manufactured by Cordis Corp. (Miami Lakes, FL), a Johnson & Johnson company. Four years after stent implantation, the risk of blood clots increased by 0.6% for Cypher and 0.4% for Taxus, according to the study. Yet neither drug-eluting stent demonstrated a statistically significant increase in its risk of stent thrombosis when compared with bare-metal stents. After four years, 99.4% of patients treated with bare-metal stents remained free of stent thrombosis versus 98.8% of patients treated with Cypher stents. The rates were similar when comparing bare-metal stents (99.1%) with Taxus stents (98.7%).

Gregg Stone, MD, vice chairman of the Cardiovascular Research Foundation (CRF; New York City) and professor of medicine at Columbia University Medical Center (New York City), said the data presented at TCT indicate "that when all aspects of long-term outcome are considered, the safety profiles for bare-metal stents and drug-eluting stents are similar."

The researchers also noted that drug-eluting stents have repeatedly demonstrated their ability to reduce the risk of restenosis—a build-up of scar tissue that could result in a narrowing or reclosing of an artery. Restenosis was a potential problem with first-generation bare-metal stents.

In addition to the CRF studies, coronary stent manufacturers Medtronic Inc. (Minneapolis), Abbott (Abbott Park, IL), and Conor Medsystems Inc. (Menlo Park, CA) also presented new data on drug-eluting stents during TCT.

Medtronic presented data indicating that its Endeavor drug-eluting stent has a low thrombosis rate that is comparable to bare-metal stents. "The data on Endeavor show that it provides the efficacy of a drug-eluting stent and the safety of a bare-metal stent, dramatically reducing repeat procedures while maintaining a favorable safety profile," said Scott Ward, president of Medtronic's vascular business.

The company also reported that its Endeavor Resolute drug-eluting coronary stent system reduces restenosis in patients with challenging medical conditions such as diabetes.

Endeavor was approved for distribution in Europe in 2005. According to Ward, the company is on track to submit its premarket approval application this fall, and Medtronic anticipates approval in the United States in mid 2007.

Additionally, Abbott reported very preliminary results of a trial involving its new bioabsorbable drug-eluting stent. The stent is made of polylactic acid, which is designed to be fully absorbed and slowly metabolized by the coronary artery. In a prepared statement, Abbott said, "The everolimus-coated stent will release the drug into the artery and then slowly absorb over time. The goal is to leave a healed natural vessel behind."

"Bioabsorbable technology holds great potential for many vascular applications," said John M. Capek, PhD, president of cardiac therapies for Abbott Vascular. "We intend to use the data from the Absorb trial to study and develop therapies that can better serve physicians and their patients. Abbott's support of this study further demonstrates the depth of our vascular pipeline and illustrates our commitment to investing in future technologies."

Recently, Abbott hit a bump in its stent development program as it announced plans to drop its ZoMaxx drug-coated stent due to poor data. The company is continuing U.S. clinical studies on the Xience stent, which received the CE mark earlier this year and went into European distribution last month. Abbott acquired the stent from Guidant upon Boston Scientific's acquisition of the company.

Also during TCT, Conor Medsystems reported results from three consecutive trials of its CoStar stent, which uses a novel drug-eluting technology that incorporates hundreds of small holes, each acting as a reservoir into which drug-polymer compositions can be loaded. CoStar also makes use of bioresorbable polymers that are absorbed by the body after the drug is released, leaving no permanent residual polymers.

However, Conor's biggest news came after TCT. Earlier this month, the company announced that it will be acquired by Johnson & Johnson's Cordis Corp. for $1.4 billion. Nicholas J. Valeriani, Johnson & Johnson's worldwide chairman for cardiovascular devices and diagnostics, said the acquisition will position Cordis "to lead the development of next-generation technologies aimed at advancing the standard of care in the treatment of coronary artery disease."

In recent months, the issue of stent safety has transcended industry interest and has become a prime focus of business and general-interest media, broadcast and cable television outlets, and popular news-oriented Web sites. Such interest is expected to be further heightened by FDA's meeting on stent safety, set for December 7–8.

Questions as to who will be on the FDA committee and the possible outcomes of the meeting are generating a great deal of speculation. Although industry observers don't expect products to be pulled from the market as a result of the meeting, it is widely believed that FDA will take a strong stand on device safety. The bar for market entry of new drug-eluting coronary stents may be raised significantly, and requirements for more-comprehensive postimplant studies are a near certainty.

How and when the issue of drug-eluting stent safety is resolved will have a major impact on the future growth and direction of the $6 billion global market for the devices. Sales in the segment are already beginning to slow, particularly in the United States.

© 2006 Canon Communications LLC

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