New Research Highlights Adverse Outcomes Associated with Unapproved Uses of Drug-coated Stents

Newswise — Research led by a team at the Methodist DeBakey Heart Center sheds light on what happens to high-risk patients who receive drug-coated stents off-label to open clogged arteries, as reported in today's Journal of the American Medical Association (JAMA).

"Our research provides a snapshot of common clinical practice and demonstrates a higher rate of major adverse cardiac events, such as heart attack and need for a repeat procedure, in patients who fall outside the parameters of the FDA's original approval for use of drug-eluting stents," said Dr. Neal Kleiman, interventional cardiologist at the Methodist DeBakey Heart Center and national co-principal investigator of the 42-center stent registry. "We need to be cautious about predicting benefits to high-risk patients based on research conducted on low-risk patients."

Placement of a stent in a patient whose disease falls outside of the inclusion criteria for the pivotal stent studies that were used for label approval is considered "off-label" use of the stent. Off-label use of medical devices or medications is common practice.

During the hospitalization phase of the study, adverse outcomes occurred in 10.9 percent of patients in the off-label group and 5.0 percent of patients in the on-label group.

This difference was primarily due to a higher frequency of heart attack in the off-label group, Kleiman said. There was no difference in the death rate between the two groups at one year.

The first drug-coated stent was approved by the FDA in 2003, based on research conducted on a narrowly defined population of low-risk patients. Since then, use of these stents has grown dramatically.

Kleiman's group designed and spearheaded the national registry that tracks "real-world" use of stents that became the basis of the JAMA article.

Researchers 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-coated, or "drug-eluting" stent between July 2004 and September 2005. The authors evaluated outcomes of death, heart attack or target lesion revascularization (the need to retreat an artery that has been stented).

"More than half of the patients in our national registry had at least one off-label characteristic. The registry findings quantify the increase in risk associated with off-label use of drug-eluting stents and identify the specific off-label characteristics that confer an increased risk. This report demonstrates the need to continue to collect data in such patients," Kleiman reports.

BackgroundAt the FDA Circulatory System Devices Advisory Panel meeting in December 2006, the statement was made that although drug-eluting stents were used frequently for off-label indications, there was a paucity of data concerning the outcomes of patients who received DES in this setting. (FDA report - December 2006: http://www.fda.gov/cdrh/news/010407.html. Kleiman's commentary on FDA report - December 2006: http://www.methodisthealth.com/stents)

Today's study has quantified in a broad population of patients the differences in outcomes among patients receiving drug-eluting stents for on-label vs. off-label indications and has identified individual predictors of adverse outcomes among patients receiving drug-eluting stents outside of the device label.

Ref:JAMA. 2007;297:2001-2009. Available pre-embargo to the media at www.jamamedia.org.)