title: Five-Year Outcome After Implantation of Zotarolimus- and Everolimus-Eluting Stents in Randomized Trial Participants and Nonenrolled Eligible Patients: A Secondary Analysis of a Randomized Clinical Trial.
abstract: Long-term follow-up after a clinical trial of 2 often-used, newer-generation drug-eluting stents (DESs) in a broad patient population is of interest. Comprehensive long-term outcome of eligible nonenrolled patients has never been reported.
  
  
  
  To assess 5-year safety and efficacy of 2 newer-generation DESs in randomized participants with non-ST-elevation acute coronary syndromes or stable angina and to evaluate long-term outcomes of nonenrolled eligible patients treated with the same DESs.
  
  
  
  The TWENTE (Real-World Endeavor Resolute vs Xience V Drug-Eluting Stent Study in Twente) trial is an investigator-initiated, patient-blinded, randomized, comparative DES trial that enrolled patients from June 18, 2008, to August 26, 2010. Most patients had non-ST-elevation acute coronary syndromes and complex lesions. Of all 1709 eligible patients, 1391 (81.4%) were treated in the TWENTE trial with zotarolimus-eluting (ZES, n = 697) or everolimus-eluting (EES, n = 694) cobalt-chromium stents. The remaining 318 eligible patients (18.6%) were not enrolled but underwent nonrandomized treatment with the same DESs. Data were analyzed from August 26, 2015, to October 11, 2016. Event rates (percentages) were derived from log-rank analysis and may differ from straightforward calculation (nominator/denominator). The 5-year follow-up of the TWENTE participants was prespecified in the trial protocol; that of the nonenrolled participants was ad hoc.
  
  
  
  Target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization.
  
  
  
  Of 1709 eligible participants, 1233 (72.1%) were men, 476 (27.9%) were women, and mean (SD) age was 64.6 (10.6) years. Among the 1370 of 1391 TWENTE trial participants (98.5% follow-up), TVF was similar between those in the ZES (16.1%) and EES (18.1%) groups (P = .36). Stent thrombosis rates were low: definite (7 of 697 [1.0%] vs 4 of 694 [0.6%]; P = .37) and occurred after more than 1 year in 3 (0.4%) with ZES vs 4 (0.6%) with EES (P = .69). The 318 nonenrolled eligible patients (308 patients [96.9%] of whom were followed up) were older and had more advanced disease than trial participants. Their TVF rate was higher than that of trial participants (71 of 318 [23.3%] vs 233 of 1391 [17.1%]; P = .02), which partly reflects a difference in cardiac mortality (23 of 318 [7.7%] vs 60 of 1391 [4.5%]; P = .03). Similar 5-year rates were found for myocardial infarction (91 of 1391 [6.7%] vs 22 of 318 [7.2%]; P = .80) and target vessel revascularization (129 of 1391 [9.7%] vs 34 of 318 [11.4%]; P = .36) between trial participants and nonenrolled eligible patients. In all eligible patients (ie, trial participants plus nonenrolled eligible patients), the TVF rate was only slightly higher than in trial participants only (18.3% vs 17.1%).
  
  
  
  Long-term outcome data from nonenrolled eligible patients support the validity of the TWENTE trial findings and present, with the trial, a strong case for the long-term safety and efficacy of the newer-generation DESs used.
  
  
  
  clinicaltrials.gov Identifier: NCT01066650.
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands2Health Technology and Services Research, MIRA-Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands.
authors.forename: Clemens
authors.initials: C
authors.lastname: von Birgelen
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Liefke C
authors.initials: LC
authors.lastname: van der Heijden
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Mounir W Z
authors.initials: MW
authors.lastname: Basalus
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Marlies M
authors.initials: MM
authors.lastname: Kok
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Hanim
authors.initials: H
authors.lastname: Sen
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Hans W
authors.initials: HW
authors.lastname: Louwerenburg
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: K Gert
authors.initials: KG
authors.lastname: van Houwelingen
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Stoel
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Frits H A F
authors.initials: FH
authors.lastname: de Man
authors.affiliation: Department of Cardiology, Ziekenhuisgroep Twente, Almelo and Hengelo, the Netherlands.
authors.forename: Gerard C M
authors.initials: GC
authors.lastname: Linssen
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Tandjung
authors.affiliation: Health Technology and Services Research, MIRA-Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands.
authors.forename: Carine J M
authors.initials: CJ
authors.lastname: Doggen
authors.affiliation: Department of Epidemiology, Medisch Spectrum Twente, Enschede, the Netherlands5Department of Research Methodology, Measurement and Data Analysis, University of Twente, Enschede, the Netherlands.
authors.forename: Job
authors.initials: J
authors.lastname: van der Palen
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
authors.forename: Marije M
authors.initials: MM
authors.lastname: Löwik
mesh_terms: D017023:Coronary Angiography; D054855:Drug-Eluting Stents; D000068338:Everolimus / Q000494:pharmacology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000601:surgery*; D018579:Patient Selection; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D011183:Postoperative Complications / Q000453:epidemiology*; D011474:Prosthesis Design; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; C489443:zotarolimus; D020123:Sirolimus