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Clinical Research in Cardiology

, Volume 105, Issue 9, pp 744–754 | Cite as

External validity of the “all-comers” design: insights from the BIOSCIENCE trial

  • Anna Franzone
  • Dik Heg
  • Lorenz Räber
  • Marco Valgimigli
  • Raffaele Piccolo
  • Thomas Zanchin
  • Kyohei Yamaji
  • Stefan Stortecky
  • Stefan Blöchlinger
  • Lukas Hunziker
  • Fabien Praz
  • Peter Jüni
  • Stephan WindeckerEmail author
  • Thomas Pilgrim
Original Paper

Abstract

Objectives

We sought to systematically evaluate the external validity of a contemporary randomized controlled stent trial (BIOSCIENCE).

Methods

Baseline characteristics and clinical outcomes of patients enrolled into the BIOSCIENCE trial at Bern University Hospital (n = 1216) were compared to those of patients included in the CARDIOBASE Bern PCI Registry at the same institution (n = 1045). The primary study endpoint was the rate of target lesion failure (TLF), defined as a composite of cardiac death, target vessel-myocardial infarction (MI) or target lesion revascularization (TLR), at 1 year.

Results

Women were underrepresented in the RCT compared to the registry (25 vs. 29.4 %, p = 0.020). Non-participants were older compared to study participants (69.2 ± 12.4 vs. 67.0 ± 11.6, p < 0.001), and had a higher prevalence of previous cerebrovascular events (10.8 vs. 5.2 %, p < 0.001), and chronic renal failure (35.5 vs. 15.6 %, p < 0.001). ST-segment elevation myocardial infarction (STEMI) and Killip class IV at presentation were more common among non-participants than participants (30.7 vs. 21.1 %, p < 0.001 and 7.8 vs. 0.4 %, p < 0.001, respectively). At 1 year, non-participants experienced a significantly higher rate of TLF, (15.0 vs. 6.5 %, p < 0.001), and patient-oriented composite endpoint (POCE), including death, MI or any repeat revascularization (21.6 vs. 11.2 %, p < 0.001). There was a significant interaction between POCE and presence or absence of an acute coronary syndrome in participants versus non-participants, respectively (p = 0.009).

Conclusions

Non-participants of this all-comers trial had a higher risk profile and adverse prognosis compared to study participants. Further efforts are needed to improve the external validity of contemporary RCTs.

Keywords

Generalizability Interventional trial Drug-eluting stents 

Notes

Compliance with ethical standards

Conflict of interest

AF has received a grant from Fondazione Umberto Veronesi. LR is on the advisory board of Abott Vascular; and received speaker fees from St. Jude Medical. RP has received a grant from Fondazione Umberto Veronesi. PJ is an unpaid steering committee or statistical executive committee member of trials funded by Abbott Vascular, Biosensors, Medtronic, and Johnson & Johnson. CTU Bern, which is part of the University of Bern, has a staff policy of not accepting honoraria or consultancy fees. SW has received research contracts to the institution from Biotronik and St Jude. TP has received travel expenses and payment for lectures from Biotronik. All other authors have no relationships relevant to the contents of this article to disclose.

Supplementary material

392_2016_983_MOESM1_ESM.pdf (395 kb)
Supplementary material 1 (PDF 395 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Anna Franzone
    • 1
  • Dik Heg
    • 2
    • 5
  • Lorenz Räber
    • 1
  • Marco Valgimigli
    • 1
  • Raffaele Piccolo
    • 1
  • Thomas Zanchin
    • 1
  • Kyohei Yamaji
    • 1
  • Stefan Stortecky
    • 1
  • Stefan Blöchlinger
    • 1
  • Lukas Hunziker
    • 1
  • Fabien Praz
    • 1
  • Peter Jüni
    • 3
    • 4
  • Stephan Windecker
    • 1
    Email author
  • Thomas Pilgrim
    • 1
  1. 1.Department of Cardiology, Swiss Cardiovascular CenterBern University HospitalBernSwitzerland
  2. 2.Institute of Social and Preventive Medicine (ISPM)University of BernBernSwitzerland
  3. 3.Applied Health Research Centre (AHRC)Li Ka Shing Knowledge Institute of St. Michael’s HospitalTorontoCanada
  4. 4.Department of MedicineUniversity of TorontoTorontoCanada
  5. 5.Clinical Trials Unit, Department of Clinical ResearchUniversity of BernBernSwitzerland

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