Stents Dominate ACC Meeting

Just as stent manufacturers seemed to be regaining their footing following reports late last year that linked drug-eluting versions of the devices to late-term thrombosis, they were hit with another bombshell. This time, the study called into question not only the efficacy of stents, but also the angioplasty procedure itself.

The findings of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) clinical study were reported at the recent meeting of the American College of Cardiology (ACC; Washington, DC) in New Orleans. The study essentially concluded that patients implanted with stents had no better clinical outcomes than those who received drug therapy alone.

The study involved 2300 coronary artery disease patients with symptoms of chronic angina and evidence of blockage. They all received aggressive medical treatment, or drug therapy, which included cholesterol-reducing statins, aspirin, nitrates, beta-blockers, and ace inhibitors. They were all counseled to eat a healthy diet, exercise, lose weight, and stop smoking. About half of the patients also received angioplasty and were implanted with a coronary stent. Patients were followed for more than four years. Over the course of the study, there were 211 deaths and heart attacks among the patients who received medical treatment plus stents, versus 202 similar incidents among those who were treated with drugs alone.

The study was sponsored by the U.S. Department of Veterans Affairs, the Canadian Institutes of Health Research, and several pharmaceutical companies.

Reaction to the study set off a firestorm that pitted interventional cardiologists, who favor stenting, against medical cardiologists, who generally rely on drugs and behavioral changes to treat cardiovascular disease. Some prominent cardiologists initially characterized COURAGE as a sea change that could fundamentally alter the treatment of cardiovascular disease. But others downplayed the findings, saying that the results were expected given the nature of the patients enrolled and the endpoints of the study.

Emotions were running high, as evidenced by the remarks of a prominent interventional cardiologist even before ACC's annual scientific session officially got underway. At a Saturday night gathering hosted by Boston Scientific Corp. (Natick, MA), Martin Leon, MD, chairman and founder of the Cardiovascular Research Foundation (New York City), tipped off attendees to the findings of the COURAGE study, which were not scheduled to be released until the following Tuesday. According to a widely cited report in the Wall Street Journal, Leon said, "The study was rigged to fail. . .and it did." According to the paper, he later added, "A lot of people have been taking shots at us, and we need to go on the offense for a while."

Clearly miffed that the embargo on the COURAGE study had been broken, ACC said it was "extremely disappointed" and characterized the action as "betraying the confidentiality of the scholarly process and the professional integrity of the scientific community." Release of the COURAGE study results was moved up to Monday as ACC said it would consider "strong sanctions against the individual or individuals involved" in breaking the embargo.

Medical cardiologists, citing what they consider a rush to angioplasty and stenting, tended to see the study as vindication of their approach. William E. Boden, MD, of Buffalo General Hospital (Buffalo, NY), a principal investigator on the COURAGE trial, said, "Medical therapy has gotten a bad rap. Patients who opt for medical therapy as the initial strategy for treatment are not putting themselves in harm's way."

Interventional cardiologists generally took issue with the fact that COURAGE studied patients with chronic stable angina. According to Gregory J. Dehmer, MD, president of the Society for Cardiovascular Angiography and Interventions (SCAI; Washington, DC), such patients represent a minority of those treated by interventional cardiologists—perhaps up to 30%. More frequently, patients treated by interventional cardiologists have heart attacks or another serious problem called unstable angina. Dehmer noted that the COURAGE study did acknowledge angioplasty and stenting as "the best therapy for patients suffering heart attack."

Donald Baim, chief medical officer at Boston Scientific, asserted that the role of stents is to relieve symptoms rather than to decrease heart attacks or death, and he called the endpoint of the COURAGE study an "unlikely thesis." He also noted that the study, which began in 2002, used bare-metal rather than drug-eluting stents.

Apart from COURAGE, other clinical studies about coronary stents presented at the ACC meeting were all generally quite positive.

Abbott (Abbott Park, IL) is expected to seek FDA approval later this year for its Xience drug-eluting stent. In results of the SPIRIT III study presented at ACC, the Xience stent met its primary and major secondary endpoints and showed statistically significant reduction in major adverse cardiac events. John M. Capek, PhD, Abbott Vascular's senior vice president, commented on the company's next steps following the positive clinical study regarding the company's completely bioabsorbable stent. "The next phase of the ABSORB study will utilize a next-generation bioabsorbable everolimus-eluting stent that incorporates several advancements designed to improve strength and deliverability."

Medtronic Inc. (Minneapolis) discussed the latest trials involving its Endeavor drug-eluting stent. Scott Ward, corporate senior vice president and president of the company's vascular business, said, "The Endeavor clinical program continues to generate strong cumulative evidence regarding Endeavor's overall performance. Patients have been 99.7% free from overall stent thrombosis, and we've seen no late stent thrombosis in our pooled clinical trials."

Cordis Corp. (Miami Lakes, FL), a Johnson & Johnson company, commented on the positive results of the MATRIX registry, a two-year study of its Cypher drug-eluting stent, in what the company described as "real world" uses. Cordis's next-generation stent, Cypher Select, received the CE mark in 2006 and is currently available in many markets outside the United States.

Despite such promising results from other trials, the implications of the COURAGE study for the future of the $6 billion stent market have yet to be fully understood.

While the COURAGE findings generated yet another round of widespread negative publicity for coronary stents in both the business and general-interest press, the response of most medtech analysts was far more measured. A few predicted a potential market decline of 5–6%, but most saw only a short-term fallout, which was likely to ebb as the findings were distilled and evaluated.

Several reports noted that while implants of drug-eluting stents decreased following last year's thrombosis scare, most of the market opted for bare-metal stents rather than relying on drug therapy alone. Even ACC, whose outgoing president initially referred to COURAGE as "a blockbuster," has since posted a more thoughtful and reasoned "Patient Update on Stents" on its Web site.

© 2007 Canon Communications LLC

Return to MX: Issues Update.