Off-label use of drug-eluting stents leads to higher rate of complications

May 24, 2007

Drug-eluting stents for non-FDA-approved indications to treat coronary artery stenosis could be associated with a higher rate of short-term complications, according to two studies published in May in the Journal of the American Medical Association. Off-label use, the studies also show, may be more prominent in the U.S. now than on-label use.

Drug-eluting stents for non-FDA-approved indications to treat coronary artery stenosis could be associated with a higher rate of short-term complications, according to two studies published in May in the Journal of the American Medical Association. Off-label use, the studies also show, may be more prominent in the U.S. now than on-label use.

Lack of reliable data on the use of drug-eluting stents outside approved indications inspired Dr. Nirat Beohar to seek some answers. He is an assistant professor of cardiology at Northwestern University and the principal investigator on one of the studies.

Beohar and colleagues analyzed data from 5541 patients prospectively enrolled at 140 academic and community hospitals who underwent angioplasty with drug-eluting coronary stenting between January and June 2005. The study sought to determine the frequency, safety, and effectiveness of drug-eluting stents for standard and off-label indications (JAMA 2007;297:1992-2000).

The investigators found that almost half of this patient population received off-label drug-eluting stents. They also found the risk of death, myocardial infarction, or thrombosis was more than twice as high in the off-label group compared with the standard-use group. The difference was statistically significant (P = 0.005).

Researchers made two important observations, however. Patients receiving drug-eluting stents for off-label and untested indications tended to present with more severe clinical profiles. This would have excluded them from the randomized trials that led to FDA approval of drug-eluting stents in the first place. They also noted that the overall rate of complications with drug-eluting stents at one year remained relatively low, even with off-label or untested use.

In the second study, Dr. Htut K. Win from Baylor College of Medicine in Houston, TX, concluded that off-label use of drug-eluting stents is more common than on-label use and linked to a higher rate of adverse angiographic and clinical outcomes.

Win and colleagues analyzed data from 3323 patients enrolled in the Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry, who received at least one drug-eluting stent between July 2004 and September 2005. The investigators assessed rates of major adverse events, including death, heart attack, and target vessel revascularization.

Drug-eluting stent intervention was off-label for about 55% of patients in the study. The risk of a major adverse cardiac event was significantly higher for the off-label group at 17.5% compared with the on-label group at 8.9% (P = 0.05).

Though randomized clinical trials have observed benefits with drug-eluting stents compared with bare-metal stents, clinicians should be cautious about extrapolating those benefits to higher risk clinical settings that have not been assessed, the researchers noted.

According to Drs. Robert A. Harrington and E. Magnus Ohman from Duke University, clinicians must take advantage of all the information resources available to make sound clinical decisions involving off- and on-label use of drug-eluting stents. Data should be integrated into a common standard of clinical practice that shows the true effects of these interventions, they wrote in an editorial article published in the same issue of JAMA.

For more information from the Diagnostic Imaging archives:

CTA revolutionizes treatment of peripheral vascular disease

Journal review: drug-eluting coronary stents

Research determines timing, tools for optimal coronary interventions

Minimally invasive PVD treatment lowers amputation rates