Outcomes and complications associated with off-label and untested use of drug-eluting stents

JAMA. 2007 May 9;297(18):1992-2000. doi: 10.1001/jama.297.18.1992.

Abstract

Context: Limited data exist regarding use of drug-eluting stents outside of approved indications in real-world settings.

Objectives: To determine the frequency, safety, and effectiveness of drug-eluting stents for off-label (restenosis, bypass graft lesion, long lesions, vessel size outside of information for use recommendation) and untested (left main, ostial, bifurcation, or total occlusion lesions) indications in percutaneous coronary intervention (PCI).

Design, setting, and patients: Observational, prospective, multicenter registry to evaluate in-hospital, 30-day, and 1-year outcomes among patients undergoing PCI between January and June 2005 in 140 US academic and community medical centers. Of 7752 PCI-treated patients, 6993 (90%) received drug-eluting stents; of these, 5851 (84%) received no other devices. Standard, off-label, and untested use was determined in 5541 (95%) of these 5851 patients, constituting the study cohort.

Main outcome measures: Frequency of off-label and untested use, 1-year repeat target vessel revascularization, and composite of death, myocardial infarction (MI), or stent thrombosis at in-hospital follow-up and during 1 year of follow-up.

Results: Of 5541 patients receiving drug-eluting stents, 2588 (47%) received stents for off-label or untested indications. Adjusted in-hospital risk of death, MI, or stent thrombosis was not statistically different with off-label or untested vs standard use. At 30 days, the risk of this composite end point was significantly higher with off-label use (adjusted hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.24-3.48; P = .005) but not untested use (adjusted HR, 1.45; 95% CI, 0.79-2.67; P = .23). Excluding early events, this end point was not different at 1 year with off-label use (adjusted HR, 1.10; 95% CI, 0.79-1.54; P = .57) or untested use (adjusted HR, 0.91; 95% CI, 0.60-1.38; P = .66). At 1 year, compared with standard use, significantly higher rates of target vessel revascularization were associated with off-label use (adjusted HR, 1.49; 95% CI, 1.13-1.98; P = .005) and untested use (adjusted HR, 1.49; 95% CI, 1.10-2.02; P = .01), although absolute rates were low (standard, 4.4% [n = 113]; off-label, 7.6% [n = 95]; untested, 6.7% [n = 72]).

Conclusions: In contemporary US practice, off-label and untested use of drug-eluting stents is common. Compared with standard use, relative early safety is lower with off-label use, and the long-term effectiveness is lower with both off-label and untested use. However, the absolute event rates remain low.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary*
  • Clopidogrel
  • Consumer Product Safety*
  • Female
  • Hospital Mortality
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Male
  • Middle Aged
  • Paclitaxel* / administration & dosage
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prospective Studies
  • Registries*
  • Risk
  • Sirolimus* / administration & dosage
  • Stents* / adverse effects
  • Stents* / statistics & numerical data
  • Survival Analysis
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Treatment Outcome
  • United States

Substances

  • Immunosuppressive Agents
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Paclitaxel
  • Sirolimus