title: Long-term outcomes following off-label use of sirolimus-eluting stent.
abstract: OBJECTIVE
  To clarify the impact of off-label use of drug-eluting stent (DES) on 5-year outcomes.
  
  
  BACKGROUND
  Studies on the outcomes of on- vs. off-label use of DES have been limited by the duration of observation.
  
  
  METHODS
  We analyzed 1937 patients from a multicenter registry that includes 95% of patients with 5-year follow-up data. We defined 10 variables as off-label indications according to the manufacturer's instructions for use, and 1665 of 1937 patients (86.0%) met the criteria for at least 1 off-label indication.
  
  
  RESULTS
  At 5 years, there were no differences in the rates of death, myocardial infarction (MI), and stent thrombosis between off-label and on-label use. The frequency of major adverse cardiac events (MACE), target lesion revascularization (TLR), non-TL but target vessel revascularization (TVR), and target vessel failure were higher in the off-label only during the first year. Among the off-label, having 2 indications was associated with TVR hazard ratio (HR) 1.62; 95% confidence interval (95%CI), 1.09-2.36 and TLR (HR, 1.90; 95%CI, 1.30-2.85). Moreover, having ≥3 off-label indications increased the risk of MACE (HR, 1.70; 95% CI, 1.23-2.40) compared with on-label use. Thrombosis rates increased with the number of off-label indications; it was 0.32% with 1, 0.69% with 2, and 3.54% with ≥3 off-label indications (p<0.001). This trend was also seen with other outcomes, except for non-TL TVR. Patients with ≥3 off-label indications had a remarkably different clinical course.
  
  
  CONCLUSIONS
  Off-label use did not increase rates of death and MI as compared with on-label use, but the number of off-label indications influenced outcomes at 5 years.
authors.affiliation: Cardiovascular Division, National Cerebral and Cardiovascular Center, Suita, Japan. Electronic address: Shamallv8@aol.com.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kotani
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikari
authors.forename: Eishou
authors.initials: E
authors.lastname: Kyo
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Yokoi
mesh_terms: D000368:Aged; D003327:Coronary Disease / Q000401:mortality / Q000628:therapy*; D016208:Databases, Factual; D054855:Drug-Eluting Stents / Q000009:adverse effects / Q000592:standards; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology; D018579:Patient Selection; D011358:Product Surveillance, Postmarketing; D012042:Registries; D012306:Risk; D020123:Sirolimus / Q000008:administration & dosage*; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020123:Sirolimus
keywords: Coronary disease; Follow-up studies; Stents