Anna Franzone1, Dik Heg2,3, Lorenz Räber1, Marco Valgimigli1, Raffaele Piccolo1, Thomas Zanchin1, Kyohei Yamaji1, Stefan Stortecky1, Stefan Blöchlinger1, Lukas Hunziker1, Fabien Praz1, Peter Jüni4,5, Stephan Windecker6, Thomas Pilgrim1. 1. Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland. 2. Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland. 3. Clinical Trials Unit, Department of Clinical Research, University of Bern, Bern, Switzerland. 4. Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada. 5. Department of Medicine, University of Toronto, Toronto, Canada. 6. Department of Cardiology, Swiss Cardiovascular Center, Bern University Hospital, 3010, Bern, Switzerland. stephan.windecker@insel.ch.
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.
RCT Entities:
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.
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