Medical Device Daily Executive Editor

Angioplasty/stenting — already getting opportunistic pushback driven by the concerns related to stent/drug-elution and those proponents favoring use of coronary artery bypass grafting (CABG) — took another body blow this week, this time from the pharma sector.

Results of the Clinical Outcomes Utilizing Percutaneous Coronary Revascularization and Aggressive Guideline-Driven Drug Evaluation (COURAGE) trial were reported at the annual scientific meeting of the American College of Cardiology (Washington) on Monday, the data indicating that stenting offers results no better than drug therapy for the treatment of stable angina.

Stent manufacturers and clinician groups committed to the value of stents have already begun to point out various limitations of those findings, but these critics are up against big-headline dissemination by the general media.

And the Street wasn't particularly happy with the news either.

Shares of Boston Scientific (Natick, Massachusetts) and Johnson & Johnson (New Brunswick, New Jersey), makers of the two FDA-approved DES devices, dropped. Boston Scientific was hit hardest with nearly an 8% decline on Monday, dropping to a four-and-one-half year low of $14.15 and rising only a bit yesterday.

In contrast, shares of Abbott Laboratories (Abbott Park, Illinois) rose nearly 5%. Abbott does not yet have an FDA -approved stent, but benefited from strong data for its Xience DES, rolled out at ACC, and the stent is expected to win that approval next year (see accompanying front-page story).

The investigators of COURAGE reported that percutaneous coronary intervention (PCI) as a primary strategy for dealing with coronary artery disease did not reduce mortality, myocardial infarction or other major cardiovascular events "when added to optimal medical therapy," meaning a drug regimen.

The study, enrolling 2,287 heart disease patients in Canada and the U.S. between 1999 and 2004, will appear in the March 29 issue of the New England Journal of Medicine.

A variety of attacks on the study conclusions were immediately issued, and several analysts indicated that they did not project any large additional reduction of stent use.

Some of the criticisms of COURAGE:

• Primary bare-metal stent use in the study. COURAGE enrollment came before the full roll-out of DES and so involved only 3% DES use. Stent proponents immediately noted that broad use of the newer DES was likely to have shown a better result for stenting. And an editorial in the NEJM accompanying the study results noted that with more DES implants there might have been fewer repeat procedures and the symptom benefit of PCI larger.

• Patient pool limitations. Patients in the study came largely from hospitals treating veterans in the U.S. and Canada, a patient population with greater compliance to drug use because they are provided free, thus not representing the general population.

• Crossover population. Donald Baim, MD, chief technology officer for Boston Scientific, and others noted that about one-third of the patients in the drug group experienced worsened symptoms and over the five-year period of the study received a follow-on PCI or CABG.

• Limited stenting application. The Society for Cardiovascular Angiography and Interventions (SCAI; Washington), issued a statement saying that the chronic stable angina patient pool studied in COURAGE represents only about 30% of those treated with stenting.

Gregory Dehmer, MD, president of SCAI, said, "More frequently, patients treated by interventional cardiologists have heart attacks or another serious problem called unstable angina. The COURAGE study did not evaluate this type of patient." He noted also that the investigators acknowledged that PCI "is the best therapy for patients suffering heart attack."

Dehmer urged putting the trial in a larger perspective.

"We are concerned that many seem to be interpreting this study as part of a huge battle among cardiologists that will shift therapy in a dramatic way, but I don't really see it shaping up that way. Although PCI is life-saving in the setting of a heart attack, it has never been promoted in any of the national treatment guidelines as saving lives or preventing heart attacks in patients with chronic stable angina. Although it is tempting to pick apart the COURAGE trial for its flaws, and there are some, doing so would remove the focus from how the results can best be used to improve patient care."

SCAI also positioned COURAGE as demonstrating the overall improved treatment of coronary artery disease.

Lawrence Biegelsen, device analyst for Prudential Financial (New York), in a report projected only a "modest negative impact" on stent use as fall-out from the trial "because stents provide some symptom benefit and there are financial incentives for stenting."

In another study dealing with stenting:

• Researchers at Miami Children's Hospital (Miami, Florida) reported on the use of stents to treat infants with congenital heart disease and concluded that "balloon extendable stent [BES] implantation in infants is safe and effective."

They said the devices "can be enlarged through serial re-dilation to keep pace" with the child's growth. The authors recommended use of stents with "adult diameter potential who do not require later surgery and that for those who will require follow-on surgery, smaller stents can be used effectively and removed or ligated safely at a later date, if needed."

The authors noted that the BES strategy had been used previously but that there has been, so far, a lack of long-term follow-up data.

Overall, 33 BES procedures were attempted in 27 patients, with the study group finally consisting of 22 patients with 26 BES implants. At the latest follow-up 21 patients were alive, with one mortality, a "late unrelated death 51 months after implantation," according to the study abstract.