FDA Advisers Unanimously Urge Approval of New Drug-Eluting Stent

GAITHERSBURG, Md., Oct. 11 -- An FDA advisory panel voted unanimously to recommend approval of a zotarolimus-eluting coronary stent made by Medtronic.

The panel said, however, added two conditions for approval:

• A five-year, 5,000-patient post-marketing study with a primary endpoint of very late stent thrombosis and a secondary endpoint of death and/or myocardial infarction.
• Labeling that includes a recommendation for 12 months dual antiplatelet therapy, which is consistent with current guidelines for drug-eluting stents.

The FDA is not required to follow the advisory panel's recommendation, but it generally does.

Medtronic is seeking approval for use of the stent in treatment of patients with de novo lesions of 27 mm or less in vessels 2.5 mm to 3.5 mm.

The c application marks the first time that a stent-maker has included more than nine months of follow-up data. Data of limited duration has been a frequent point of criticism of previous FDA approvals of drug-eluting devices.

The FDA approved both the sirolimus-eluting stent (Cypher) and the paclitaxel-eluting stent (Taxus) on the basis of nine-month follow-up. Longer-term studies and data from several registries have reported an increase in stent thrombosis starting 12 months or later after implant.

Medtronic reported one-year follow-up on 1,301 patients and two-year follow-up on 1,287 patients. After a year, the stent thrombosis rate was 0.1% with Endeavor, versus 1.3% with Taxus and 1.2% with Cypher at one year.

If the FDA follows the recommendation, the approval could prove to be a major boost to the drug-eluting stent market, which has seen its market share drop from more than 90% of percutaneous coronary interventions a year ago, to just over 60% of the market.

The problems for drug-eluting stents began in March 2006 when researchers from Basel, Switzerland, reported an increase in late-stent thrombosis in a "real-world" study of stent patients. (See: Late Thrombotic Events Take Off When Stent Patients Stop Plavix)

Then in September 2006 a meta-analysis of published stent trials found a statistically significant increase in mortality with the sirolimus-eluting (Cypher) stent compared with bare-metal stents.

That report ignited a firestorm of controversy at the 2006 ESC meeting in Barcelona that has continued to stir passions over the past 12 months. The fallout from the Barcelona meeting included an FDA hearing on stent safety in December, and new guidelines on drug-eluting stent use from the American Heart Association/American College of Cardiology/Society of Cardiographic Angiography and Interventions.