title: Differential relative efficacy between drug-eluting stents in patients with bare metal and drug-eluting stent restenosis; evidence in support of drug resistance: insights from the ISAR-DESIRE and ISAR-DESIRE 2 trials.
abstract: OBJECTIVE
  In drug-eluting stent (DES) restenosis, the contribution of drug hyporesponsiveness is poorly defined. We sought to evaluate if, in the setting of treatment for in-stent restenosis, the relative efficacy of sirolimus-eluting stents (SES) and of paclitaxel-eluting stents (PES) depends on the underlying substrate in which the stents are implanted, i.e., on whether the restenosis occurs within bare metal stents or within SES.
  
  
  RESULTS
  We pooled data from the ISAR-DESIRE and ISAR-DESIRE 2 randomised trials and analysed outcomes in SES-treated and PES-treated patients. In all, 650 patients were included. Angiographic follow-up was available for 87% of patients. In SES-treated patients, both late loss (LL) and percentage diameter stenosis (%DS) were lower in patients treated for bare metal stent restenosis compared with SES restenosis (0.21±0.59 mm versus 0.41±0.66 mm, p=0.007; 27.6±19.4% versus 34.0±20.9%, p=0.015, respectively). In PES-treated patients, LL and %DS were similar in patients treated for bare metal stent restenosis compared with SES restenosis (0.48±0.59 mm versus 0.39±0.71, p=0.47; 33.5±22.2% versus 32.7±18.6%, p=0.75, respectively). Similarly, in terms of overall clinical efficacy, in SES-treated patients clinical outcomes were better in patients with bare metal stent restenosis compared with SES restenosis while in PES-treated patients outcomes were similar in both groups. At multivariate analyses the use of SES to treat restenosis within SES was predictive of both higher LL and %DS.
  
  
  CONCLUSIONS
  The efficacy of sirolimus-eluting but not paclitaxel-eluting stents is significantly reduced when used for treatment of SES restenosis as compared to bare metal stent restenosis. The lower antirestenotic efficacy following SES implantation in patients with SES restenosis may support a role for drug resistance in restenosis within these stents.
authors.affiliation: Deutsches Herzzentrum, Technische Universität, Munich, Germany.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Byrne
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cassese
authors.forename: Thomas
authors.initials: T
authors.lastname: Windisch
authors.forename: Lamin A
authors.initials: LA
authors.lastname: King
authors.forename: Michael
authors.initials: M
authors.lastname: Joner
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Tada
authors.forename: Julinda
authors.initials: J
authors.lastname: Mehilli
authors.forename: Jürgen
authors.initials: J
authors.lastname: Pache
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
mesh_terms: D023903:Coronary Restenosis / Q000628:therapy; D004351:Drug Resistance; D054855:Drug-Eluting Stents; D006801:Humans; D008670:Metals; D017239:Paclitaxel; D020123:Sirolimus; D016896:Treatment Outcome
chemical_list: D008670:Metals; D017239:Paclitaxel; D020123:Sirolimus