title: Angiographic surrogate end points in drug-eluting stent trials: a systematic evaluation based on individual patient data from 11 randomized, controlled trials.
abstract: OBJECTIVE
  We sought to validate 4 angiographic measures as potential surrogates for clinical restenosis (target lesion revascularization [TLR]) after stent implantation.
  
  
  BACKGROUND
  Given the low revascularization rates with drug-eluting stents (DES), an angiographic surrogate of TLR is desirable to reduce the sample size required to demonstrate efficacy in future trials of antirestenosis devices.
  
  
  METHODS
  We evaluated 4 potential angiographic measures (late loss [LL] and percent diameter stenosis [%DS], both in-stent and in-segment) as a surrogate for TLR at 1 year. From 11 multicenter, prospective randomized stent trials, 9 comparing DES with bare-metal stents (BMS) and 2 comparing different DES, individual data on 5,381 patients with a single treated lesion and follow-up angiography at 6 to 9 months were analyzed.
  
  
  RESULTS
  By 4 well-defined criteria of surrogacy, LL and %DS strongly predicted the risk of TLR, with in-segment %DS being the most highly predictive (approximately 0.95). Differences in TLR risk were fully explained statistically by their differences in LL or %DS, although LL as a surrogate was dependent on vessel size whereas %DS was not. However, because of the curvilinearity of the logistic model, trials comparing 2 effective DES can have significant differences in mean LL and %DS but small expected differences in TLR risk, especially at the lower ranges of LL and %DS.
  
  
  CONCLUSIONS
  From in-stent and in-segment LL and %DS measures, logistic models can reliably estimate TLR rates for DES and BMS. These angiographic measures are thus suitable surrogate markers for clinical stent efficacy and can be used as primary end points in future DES trials to significantly reduce sample size.
authors.affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Lansky
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Popma
authors.forename: Martin P
authors.initials: MP
authors.lastname: Fahy
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Na
authors.forename: George
authors.initials: G
authors.lastname: Dangas
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Moses
authors.forename: Tereza
authors.initials: T
authors.lastname: Pucelikova
authors.forename: David E
authors.initials: DE
authors.lastname: Kandzari
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ellis
authors.forename: Martin B
authors.initials: MB
authors.lastname: Leon
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000000981:diagnostic imaging; D023921:Coronary Stenosis / Q000601:surgery*; D054855:Drug-Eluting Stents; D006801:Humans; D016896:Treatment Outcome