Off-label and untested use of drug-coated stents appears widespread

May 08, 2007

The off-label and untested use of drug-coated stents in the treatment of coronary artery blockage is common in U.S. practice, and ischemic complication rates are higher among patients receiving drug-coated stents for off-label indications, according to two studies in the May 9 issue of JAMA.

Stents are tiny mesh tubes used to prop open an artery after balloon angioplasty is used to open an obstructed coronary artery. The newer drug-eluting stents are normal metal stents coated with a drug that is known to interfere with the process of restenosis (re-obstruction). Data on the use of drug-eluting stents outside of approved indications in real-world settings are limited, according to background information in the articles.

Nirat Beohar, M.D., of Northwestern University Feinberg School of Medicine, Chicago, and colleagues analyzed data from the D.E.S.cover Registry - a prospective, multicenter, observational study conducted at 140 U.S. academic and community hospitals, and consisting of 7,752 patients who underwent percutaneous coronary intervention (PCI, balloon angioplasty) between January and June 2005. The study objective was to determine the frequency, safety, and effectiveness of drug-eluting stents for off-label and untested indications. Off-label indications included use of stents for restenosis, bypass graft lesion, and long lesions. Untested indications included left main, ostial, bifurcation, or total occlusion lesions.

The authors observed that approximately half of all use of drug-eluting stents occurs in off-label or untested settings. "Of 5,541 patients receiving drug-eluting stents, 2,588 (47 percent) received stents for off-label or untested indications," they write.

"Compared with patients receiving drug-eluting stents for standard indications, those receiving such stents for off-label and untested indications tended to present with more severe clinical profiles, which would have excluded these patients from the pivotal randomized trials that led to FDA approval of drug-eluting stents," they continue.

The authors report a significant difference in clinical outcome for patients in the off-label group was clearly evident by the 30-day follow-up. "Both observed and adjusted analyses indicated a greater than two-fold higher risk of death, MI [myocardial infarction, heart attack], or stent thrombosis [formation of a blood clot]," they write.

"Compared with standard use, short-term outcomes appear to be worse with off-label and untested use," the authors conclude. "However, even with off-label or untested use of drug-eluting stents, overall absolute event rates both in hospital and at 12 months following PCI remain relatively low."

(JAMA. 2007;297:1992-2000. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Higher Rate of Adverse Outcomes Associated With Off-Label Use of Drug-Coated Stents

In a related article, Htut K. Win, M.D., M.R.C.P, of Baylor College of Medicine, Houston, and colleagues report that off-label use of drug-eluting stents is more common than on-label use and is associated with a persistently higher rate of adverse angiographic and clinical outcomes.

The authors assessed rates of major adverse cardiac events during the index admission and one year after the implantation of drug-eluting stents in patients with high-risk angiographic and clinical features. They analyzed data from 3,323 patients enrolled in the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) registry, who received at least one drug-eluting stent between July 2004 and September 2005. The authors evaluated composite clinical outcomes of death, heart attack, or target vessel revascularization at the index admission, and at one year.

"Of the 3,323 patients, 1,817 (54.7 percent) had at least one off-label characteristic," the authors report.

During the index hospitalization, the composite clinical outcome occurred in 198 (10.9 percent) patients in the off-label group and 76 (5.0 percent) patients in the on-label group.

"The primary composite outcome occurred more often in the off-label group," they write. "This difference was primarily due to a higher frequency of MI [heart attack] in the off-label group."

There was no difference in the death rate between the two groups at one year. The composite outcome and stent thrombosis occurred more often in the off-label group.

"Several specific off-label angiographic and clinical characteristics seemed to be associated with the highest incidence of adverse clinical events," the authors conclude. "Clinicians should be cautious about extrapolating the benefits of drug-eluting stents compared with bare-metal stents that were observed in randomized clinical trials to higher-risk clinical settings that have not been assessed."

(JAMA. 2007;297:2001-2009. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: The Enigma of Drug-Eluting Stents

In an accompanying editorial, Robert A. Harrington, M.D., and E. Magnus Ohman, M.D., of Duke University Medical Center, Durham, North Carolina, write that drug-eluting stenting is clearly a breakthrough technology - but clinicians must be careful not to succumb to the hope and hype of a product based on limited approval data.

"Clinicians must take advantage of all the information sources available (RCTs [randomized controlled trials], observational studies, and clinical vigilance) in making clinical decisions," they write. "Moreover, it is essential to harness the power of this disparate information by working toward common data standards, efficient methods of data aggregation, and systems that allow rapid performance of clinical trials that can be integrated into clinical practice and that can provide a true reflection of the patients receiving these sometimes enigmatically evolving intervention."

(JAMA. 2007;297:2028-2030. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.
For more information, contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or e-mail .

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