Wednesday, October 24, 2007

Cracks in Crucible of Evidence-Based Medicine Create "Climate of Calamity"

The real story emerging from this year's Transcatheter Cardiovascular Therapeutics (TCT) meeting in Washington, DC, is not the news per se regarding specific clinical trial results or new device technologies. Instead, it is the story behind the story that is making news.

Interventional cardiology has been built on the back of evidence-based medicine and, as the leading interventional cardiovascular conference, TCT--now in its 19th year--has long been the crucible for the unveiling of data from the randomized clinical trials and other studies that are the currency accounting for this specialty's historically rapid adoption of new device technology.

That methodology, however, has come under attack in the last year, creating what Martin B. Leon, MD, TCT's co-director, calls a "climate of calamity". The crisis coincides with the 30th anniversary of the procedure that has built the specialty--percutaneous coronary interventions--and is occurring in the industry's only true blockbuster product (at $5.5bn worldwide): drug-eluting stents.

The snowball that started the avalance was the release of data from a Swedish registry at last year's European Society of Cardiology meeting that raised concerns about DES safety in small numbers of cases due to problems with late-stent thrombosis. Other studies followed reporting similar problems, while still other trial results also challenged PCI's efficacy, e.g., the COURAGE study.

The result as evidenced by the tenor at this year's TCT: interventional cardiology is a specialty under attack. For the first time, both PCI procedures and DES stent usage are on the decline, in the latter's case, precipitously. According to Leon, PCI procedures have dropped by 10% in the last year, and DES penetration has fallen in the US from nearly 90% in January 2006 to around 60% in September 2007. Contributing to this crisis, in Leon's view: economic issues, the media, and regulatory challenges.

Leon and TCT co-director, Gregg W. Stone, MD, are using this year's conference as a pulpit to urge the specialty to essentially take a second look at evidence-based medicine, this time with a more critical eye. Indeed, one example they point to as indicating the need for a more balanced perspective, is that the most recent data from the same Swedish registry that caused much of the initial DES commotion, when released last month in Vienna at this year's ESC meeting, inexplicably showed improved patient outcomes with DES, not the increased risk found in the two prior years.

Nevertheless, the challenges to evidence-based medicine look to have a long-term impact on device innovation and product adoption. That was clear in a panel discussion following the release of generally positive data from the ENDEAVOR IV trial concerning Medtronic's Endeavor DES, which an FDA panel recently recommended for approval and is likely to be the next DES to hit the US market. Indeed, improved safety is seen as a potential advantage of Endeavor over the drug-eluting stents currently on the market, due in part to thinner struts and other design features. One area of concern: Endeavor showed higher late lumen loss than the Taxus DES, although that did not translate into any difference in restenosis. (Late lumen loss is used as a surrogate endpoint in clinical trials for restenosis.)

Despite Endeavor's apparent safety benefits, Mitchell Krucoff, MD, of Duke University Medical Center, one of the panelists, pointed to the higher late loss numbers as a concern, noting, "That would cause me to think twice about which drug-eluting stent to pull of the shelf when treating more complex patients."

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