title: Differential clinical outcomes after 1 year versus 5 years in a randomised comparison of zotarolimus-eluting and sirolimus-eluting coronary stents (the SORT OUT III study): a multicentre, open-label, randomised superiority trial.
abstract: BACKGROUND
  In head-to-head comparisons of coronary drug-eluting stents, the primary endpoint is traditionally assessed after 9-12 months. However, the optimum timepoint for this assessment remains unclear. In this study, we assessed clinical outcomes at up to 5 years' follow-up in patients who received two different types of drug-eluting stents.
  
  
  METHODS
  We undertook this multicentre, open-label, randomised superiority trial at five percutaneous coronary intervention centres in Denmark. We randomly allocated 2332 eligible adult patients (≥18 years of age) with an indication for drug-eluting stent implantation to the zotarolimus-eluting Endeavor Sprint stent (Medtronic, Santa Rosa, CA, USA) or the sirolimus-eluting Cypher Select Plus stent (Cordis, Johnson & Johnson, Warren, NJ, USA). Randomisation of participants was achieved by computer-generated block randomisation and a telephone allocation service. The primary endpoint of the SORT OUT III study was a composite of major adverse cardiac events-cardiac death, myocardial infarction, and target vessel revascularisation-at 9 months' follow-up. In this study, endpoints included the occurrence of major adverse cardiac events and definite stent thrombosis at follow-up times of up to 5 years. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00660478.
  
  
  RESULTS
  We randomly allocated 1162 patients to receive the zotarolimus-eluting stent and 1170 to the sirolimus-eluting stent. At 5-year follow-up, rates of major adverse cardiac events were similar in patients treated with both types of stents (zotarolimus-eluting stents 197/1162 [17.0%] vs sirolimus-eluting stents 182/1170 [15.6%]; odds ratio [OR] 1.10, 95% CI 0.88-1.37; p=0.40). This finding was indicative of the directly contrasting results for rates of major adverse cardiac events at 1-year follow up (zotarolimus 93/1162 [8.0%] vs sirolimus 46/1170 [3.9%]; OR 2.13, 95% CI 1.48-3.07; p<0.0001) compared with those at follow-up between 1 and 5 years (104 [9.0%] vs 136 [11.6%]; OR 0.78, 95% CI 0.59-1.02; p=0.071). At 1-year follow-up, definite stent thrombosis was more frequent after implantation of the zotarolimus-eluting stent (13/1162 [1.1%]) than the sirolimus-eluting stent (4/1170 [0.3%]; OR 3.34, 95% CI 1.08-10.3; p=0.036), whereas the opposite finding was recorded for between 1 and 5 years' follow-up (zotarolimus-eluting stent 1/1162 [0.1%] vs sirolimus-eluting stent 21/1170 [1.8%], OR 0.05, 95% CI 0.01-0.36; p=0.003). 26 of 88 (30%) target lesion revascularisations in the zotarolimus-eluting stent group occurred between 1 and 5 years' follow-up, whereas 54 of 70 (77%) of those in the sirolimus-eluting stent group occurred during this follow-up period.
  
  
  CONCLUSIONS
  The superiority of sirolimus-eluting stents compared with zotarolimus-eluting stents at 1-year follow-up was lost after 5 years. The traditional 1-year primary endpoint assessment therefore might be insufficient to predict 5-year clinical outcomes in patients treated with coronary drug-eluting stent implantation.
  
  
  BACKGROUND
  Cordis and Medtronic.
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark. Electronic address: michael.maeng@ki.au.dk.
authors.forename: Michael
authors.initials: M
authors.lastname: Maeng
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aalborg Hospital, Aalborg, Denmark.
authors.forename: Hans Henrik
authors.initials: HH
authors.lastname: Tilsted
authors.affiliation: Department of Cardiology, Odense University Hospital, Odense, Denmark.
authors.forename: Lisette Okkels
authors.initials: LO
authors.lastname: Jensen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Lars Romer
authors.initials: LR
authors.lastname: Krusell
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Kaltoft
authors.affiliation: Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Kelbæk
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aalborg Hospital, Aalborg, Denmark.
authors.forename: Anton B
authors.initials: AB
authors.lastname: Villadsen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aalborg Hospital, Aalborg, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Ravkilde
authors.affiliation: Department of Cardiology, Odense University Hospital, Odense, Denmark.
authors.forename: Knud Nørregaard
authors.initials: KN
authors.lastname: Hansen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Evald Høj
authors.initials: EH
authors.lastname: Christiansen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aalborg Hospital, Aalborg, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Aarøe
authors.affiliation: Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark.
authors.forename: Jan Skov
authors.initials: JS
authors.lastname: Jensen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Steen Dalby
authors.initials: SD
authors.lastname: Kristensen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Leif
authors.initials: L
authors.lastname: Thuesen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Madsen
authors.affiliation: Department of Cardiology, Odense University Hospital, Odense, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Thayssen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Henrik Toft
authors.initials: HT
authors.lastname: Sørensen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Jens Flensted
authors.initials: JF
authors.lastname: Lassen
mesh_terms: D000368:Aged; D003324:Coronary Artery Disease / Q000628:therapy; D023903:Coronary Restenosis / Q000517:prevention & control; D003328:Coronary Thrombosis / Q000209:etiology; D054697:Cytostatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D054855:Drug-Eluting Stents / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D062645:Percutaneous Coronary Intervention / Q000295:instrumentation*; D012107:Research Design; D016037:Single-Blind Method; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D054697:Cytostatic Agents; C489443:zotarolimus; D020123:Sirolimus