Angiographic surrogate end points in drug-eluting stent trials: a systematic evaluation based on individual patient data from 11 randomized, controlled trials.
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.
Pocock
Stuart J
SJ
London School of Hygiene and Tropical Medicine, London, United Kingdom.
Lansky
Alexandra J
AJ
Mehran
Roxana
R
Popma
Jeffrey J
JJ
Fahy
Martin P
MP
Na
Yingbo
Y
Dangas
George
G
Moses
Jeffrey W
JW
Pucelikova
Tereza
T
Kandzari
David E
DE
Ellis
Stephen G
SG
Leon
Martin B
MB
Stone
Gregg W
GW
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