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2-year outcome of the 3-arm BIO-RESORT randomized trial in all-comer patients
treated with contemporary DES
Marlies M. Kok, MDThoraxcentrum Twente, MST, Enschede, the Netherlands
On behalf of the BIO-RESORT Investigators (PI: C. von Birgelen, MD, PhD, FESC)
Potential conflicts of interest
Speaker's name : Marlies M. Kok, MD – Enschede, the Netherlands
☑ I have the following potential conflicts of interest to report:
Receipt of grants / research supports: Institutional research grants
from Biotronik, Boston Scientific and Medtronic
BIO-RESORT
Background
• Modern biodegradable coating DES, such as the sirolimus-eluting Orsiro and everolimus-eluting Synergy stents, combine flexible thin-strut designs with thin bioresorbable drug-eluting coatings.
• The polymer coating of the Synergy stent is resorbed within 4 months, the coating of the Orsiro stent degrades after >12 months, which is why the present follow-up of this randomized clinical trial beyond the primary clinical endpoint at 12 months is of great interest.
• The present, large scale BIO-RESORT randomized trial has demonstrated non-inferiority of the biodegradable polymer Orsiro and Synergy stents versus the durable polymer Resolute Integrity stent at 1-year follow-up. At 1-year follow-up 85.6% of the patients were on DAPT1.
1. von Birgelen et al. BIO-RESORT 1-Year Outcome. Lancet 2016; 388:2607-2617 / LBCT session TCT 2016, Washington DC (USA)
BIO-RESORT
Aim of the study
• To evaluate in all-comer PCI patients the 2-year safety and efficacy of treatment with contemporary very thin-strut biodegradable polymer Synergy and Orsiroversus thin-strut Resolute Integrity DES.
BIO-RESORT
Durable Polymer DES
Biodegradable Polymer
DES
Resolute Integrity
CoCr-ZES
Synergy
PtCr-EES
Orsiro
CoCr-SES
Thickness (µm) of uncoated strut
Data from manufacturers’ information (modified, extended) * Synergy‘s platinum chromium strut thickness is 74 µm for stent diameters ≤ 2.5 mm, 79 µm for stent diameters 3.0 – 3.5 mm, and 81 µm for stent diameter 4.0 mm. ** Orsiro‘s cobalt chromium strut thickness is 60 µm for stent diameters ≤ 3.0 mm, and 80 µm for stentdiameters > 3.0 mm; Orsiro has an asymmetrical, conformal distribution of the PLLA coating (abluminal coatingis thicker) on a very thin passive coating of silicon carbide.
Distribution, type and thickness (µm) of polymer coating
Circumfer. 6/side
BioLinxTM
Abluminal 4
PLGA, PCL
Circumfer.
4-7/side
PLLA**
91 74* 60**
Synergy and Orsiro stents use highly dissimilar biodegradablecoatings (i.e. different type, amount and degradation speed of polymer).
BIO-RESORTBIO-RESORT: Study Devices
BIO-RESORTBIO-RESORT: Study Devices
SYNERGY RESOLUTE
INTEGRITY
ORSIRO
Coatingcharacteristics
BiodegradableAbluminal
DurableCircumferential
Symmetrical
BiodegradableCircumferentialAsymmetrical
Bare strut thickness, μm
74(3.0 – 3.5 mm: 79,4.0 mm stent: 81)
91 60(≥ 3.5 mm stents: 80)
Coating thickness, μm 4 5.6 7.4 / 3.5 (ab-/luminal)
Coated strut thickness, μm (of smallest stent)
78 102 71
Metal Platinum-chromium Cobalt-chromium Cobalt-chromium
Polymer PLGA (poly [lactic-co-glycolic acid]
polymer) coating
BioLinx®, a blend of hydrophobic C10,
hydrophilic C19, and poly-vinyl pyrrolidone
PLLA (poly [L-lactide] acid) (BIOlute®), on thin
amorphous siliconcarbide (proBIO®)
Drug Everolimus Zotarolimus Sirolimus
Drug release time, mo. 3 6 3.3
Degradation time, mo. 4 --- < 24
BIO-RESORT: Trial Design
Primary endpoint Target Vessel Failure (composite of cardiac death, target vessel-related myocardial infarction, or
clinically driven target vessel revascularization) to test 2 independent hypotheses that the safety and efficacy of both ORSIRO and SYNERGY is non-inferior to the reference device RESOLUTE INTEGRITY
Secondary endpoints Death ∙ myocardial infarction (MI) ∙ repeat revascularization ∙ stent thrombosis ∙ TLF ∙ etc.
Investigator-initiated, multicenter, assessor and patient-blinded, three-arm, randomized, non-inferiority trial ∙Visits to outpatient clinic, questionnaire or telephone follow-up ∙ No routine angiographic follow-up ∙
Independent monitoring and clinical event adjudication (CEC) ∙ Supervision by DSMB
30 days 1 year 5 years
Inclusion criteria: Pat. ≥ 18 yrs.; PCI with DES required; informed consent; ability and willingness to comply with study procedures and follow-up
Exclusion criteria: Participation in another drug or device RCT before reaching primary EP; life expectancy < 1 year; planned surgery < 6 mo’s
unless DAPT maintained; known pregnancy; known intolerance to DES, anticoagulants or antiplatelet drugs preventing DAPT
3,514 all-comers were 1:1:1 randomized to DES type and assessed
All-comer patients: any patient who requires a percutaneous coronary intervention with DES implantation
Patients with any clinical syndrome, number of target lesions or vessels, any lesion length, vessel size, etc.
2 years 3 years 4 years
Zotarolimus-eluting
RESOLUTE INTEGRITYSirolimus-eluting
ORSIROEverolimus-eluting
SYNERGY
BIO-RESORT Study Sites: Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede ∙ Rijnstate Hospital, Arnhem ∙ Haga Hospital, The Hague ∙ Albert Schweitzer Hospital, Dordrecht; all in the Netherlands ∙ Enrollment from December 21, 2012 to August 24, 2015 ∙
PI: C. von Birgelen, MD PhD, TC Twente, Enschede, the Netherlands. This investigator-initiated study is equally funded by Biotronik, Boston Scientific & Medtronic.
3,472 patients (98.8%) completed 2-year follow-up or had died. 11 Patients lost to follow-up, 31 patients withdrew consent
BIO-RESORT
Patients & Lesions
PatientsSynergy
n = 1,172Resolute Integrity
n = 1,173Orsiro
n = 1,169
Mean age at randomization 64.0 years 63.6 years 64.2 years
Men 72.1 % 72.3 % 73.1 %
Women 27.9 % 27.7 % 26.9 %
Clinical syndrome at index PCIAny ACS 69.6 % 69.5 % 70.0 %
STEMI 32.2 % 27.8 % 31.7 %
NSTEMI 21.1 % 23.0 % 20.4 %
Unstable angina 16.4 % 18.7 % 17.9 %
Stable angina 30.4 % 30.5 % 30.0 %
Lesions and proceduresSynergy
n = 1,532 lesionsResolute Integrityn = 1,580 lesions
Orsiron = 1,551 lesions
Simple target lesions (types A or B2) 29.0 % 27.8 % 26.3 %
Complex target lesions (types B2 or C) 71.0 % 72.2 % 73.7 %
Severely calcified target lesions 19.3 % 20.7 % 20.4 %
Direct stenting performed (no pre-dilation) 22.3 % 20.4 % 23.0 %
Post-dilation of stent performed 77.7 % 73.3 % 74.0 %
BIO-RESORT
Results: Target Vessel FailureBIO-RESORT
Lancet 2016; 388: 2607–17 1-year follow-up
Results: Target Vessel FailureBIO-RESORT
Results: TVF Components
At 2-year follow-up, there was no statistically significant difference between DES groups in the components of target vessel failure (TVF)
Cardiac death at 2 year
Target vessel myocardial infarction at 2 year Target vessel revascularisation at 2 year
BIO-RESORT
Target lesion failure (TLF) at 2-year Landmark analysis of TLF
Landmark analysis between 1 and 2 year follow-up showed a significantly lower rate of the secondary endpoint TLF (composite of cardiac death, any MI or clinically driven TLR) in patients of the SES arm versus the ZES arm
BIO-RESORTResults: Target Lesion Failure
Target lesion revascularisation (TLR) at 2-year Landmark analysis of TLR
Landmark analysis between 1 and 2 year follow-up showed a significantly lower rate of TLR in the SES arm versus the ZES arm
BIO-RESORTResults: TLR
Definite-or-probable stent thrombosis rates were low and similar among groups
Definite-or-probable stent thrombosis at 2-year follow-up
BIO-RESORT Results: Stent Thrombosis
Why is this study important?
• Reliable outcome data of contemporary DES in all-comers are of significant interest, particularly considering the use of differentbiodegradable DES with dissimilar polymers and degradationtimes.
• BIO-RESORT is the first randomized clinical trial that examines the everolimus-eluting Synergy stent in all-comers.
• Low TVF rates were observed in a complex all-comers population that includes a huge proportion of patients with acute coronary syndromes (70%) and more than 30% of all patients presenting with STEMI.
• Landmark analyses provided a signal that the use of the Orsirosirolimus-eluting stent might reduce the risk of repeat revascularisation after the first year of follow-up.
BIO-RESORT
Summary & Conclusions
Very thin-strut biodegradable polymers DES with flexible designs and refined coatings promotere-endothelialization and reduce the risk of ischemic coronary events. The randomised, multicentre BIO-RESORT trial compared in 3,514 all-comers the 2-year outcome data (98.8% follow-up) after treatment with the very thin-strut Orsiro and Synergy biodegradable polymerDES versus the thin-strut Resolute Integrity durable polymer DES.
Conclusion
• The combination of very thin strut stents with biodegradablepolymers was associated with a safety and efficacy that during the first 2 years from implantation in all-comers was similar to DES with durable polymer coating.
• The landmark analyses provided a signal that use of the biodegradable polymer sirolimus-eluting Orsiro stent might reducethe risk of repeat revascularisation after the first year of follow-up. Further long-term data will be of great interest.
BIO-RESORT
The investigator-initiated randomized BIO-RESORT trial was equally funded by Biotronik, Boston Scientific and Medtronic.
BIO-RESORT
BIO-RESORTTrial Organization
Study Centers and Local PIsThoraxcentrum Twente, Enschede
C. von Birgelen, MD PhDRijnstate Hospital, Arnhem
P. Danse, MD PhDHaga Hospital, Den Haag
C. Schotborgh, MDAlbert Schweitzer Hospital, Dordrecht
M. Scholte, MD
Study CoordinationCRE, Enschede
M. Kok, MDG. Zocca, MDR. Buiten, MDL. van der Heijden, MD, PhDK. Tandjung, MD PhD
Steering CommitteeC. von Birgelen, MD PhD (Study PI)P. Danse, MD PhDM. Hartmann, MD PhDK. van Houwelingen, MDJ. Louwerenburg, MDF. de Man, MD PhDM. Scholte, MDC. Schotborgh, MDM. Stoel, MD PhD
Statistical AnalysisM. Kok, MDG. Zocca, MDL. van der Heijden, MD, PhDC. Doggen, PhD (Statistical supervisor)
Data Management, Analysis and Follow-upCRE, Enschede
Monitoring and Organization ofClinical Event AdjudicationDiagram, Zwolle
Kok M.M. et al. EuroIntervention 2018; in press – simultaneously online published (2-year follow-up)von Birgelen C. et al. Lancet 2016; 388: 2607–17 (1-year follow-up)
Manuscript with further details is free available on the homepage of EuroIntervention
DOI: 10.4244/EIJ-D-18-00336
Two-year clinical outcome of all-comers treated with three highly dissimilar contemporary coronary drug-eluting stents
in the randomised BIO-RESORT trial
Marlies M. Kok, MD1*, Paolo Zocca, MD1*, Rosaly A. Buiten, MD1, Peter W. Danse, MD PhD2, Carl E. Schotborgh, MD3, Martijn Scholte, MD4,
Marc Hartmann, MD PhD1, Martin G. Stoel, MD PhD1, K. Gert van Houwelingen, MD1, Gerard C.M. Linssen, MD PhD5, Carine J.M. Doggen, PhD6, Clemens von Birgelen, MD PhD1,6
1 Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands
2 Department of Cardiology, Rijnstate Hospital, Arnhem, the Netherlands3 Department of Cardiology, Haga Hospital, The Hague, the Netherlands4 Department of Cardiology, Albert Schweitzer Hospital, Dordrecht, the Netherlands5 Department of Cardiology, Hospital Group Twente, Almelo and Hengelo, the Netherlands6 Department of Health Technology and Services Research, MIRA – Institute of Technical
Medicine and Biomedical Technology, University of Twente, Enschede, the Netherlands* M.M. Kok and P. Zocca contributed equally to this manuscript.
Summary & Conclusions
Very thin-strut biodegradable polymers DES with flexible designs and refined coatingspromote re-endothelialization and reduce the risk of ischemic coronary events. The randomised, multicentre BIO-RESORT trial compared in 3,514 all-comers the 2-year outcome data (98.8% follow-up) after treatment with the very thin-strut Orsiro and Synergy biodegradable polymer DES versus the thin-strut Resolute Integrity durable polymer DES.
• The combination of very thin strut stents with biodegradablepolymers was associated with a safety and efficacy that during the first 2 years from implantation in all-comers was similar to DES with durable polymer coating.
• The landmark analyses provided a signal that use of the biodegradable polymer sirolimus-eluting Orsiro stent might reducethe risk of repeat revascularisation after the first year of follow-up. Further long-term data will be of great interest.
BIO-RESORT