2-year outcome of the 3-arm BIO-RESORT randomized trial in all-comer patients treated with contemporary DES

Transcription

1 2-year outcome of the 3-arm BIO-RESORT randomized trial in all-comer patients treated with contemporary DES Marlies M. Kok, MD Thoraxcentrum Twente, MST, Enschede, the Netherlands On behalf of the BIO-RESORT Investigators (PI: C. von Birgelen, MD, PhD, FESC)

2 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

3 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 DAPT von Birgelen et al. BIO-RESORT 1-Year Outcome. Lancet 2016; 388: / LBCT session TCT 2016, Washington DC (USA)

4 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 Orsiro versus thin-strut Resolute Integrity DES.

5 BIO-RESORT: Study Devices Durable Polymer DES Biodegradable Polymer DES Resolute Integrity CoCr-ZES Synergy PtCr-EES Orsiro CoCr-SES Synergy and Orsiro stents use highly dissimilar biodegradable coatings (i.e. different type, amount and degradation speed of polymer). Thickness (µm) of uncoated strut 91 74* 60** Distribution, type and thickness (µm) of polymer coating Circumfer. 6/side Abluminal 4 BioLinx TM PLGA, PCL Circumfer. 4-7/side PLLA** 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 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 stent diameters > 3.0 mm; Orsiro has an asymmetrical, conformal distribution of the PLLA coating (abluminal coating is thicker) on a very thin passive coating of silicon carbide.

6 BIO-RESORT: Study Devices Coating characteristics Bare strut thickness, μm SYNERGY Biodegradable Abluminal 74 ( mm: 79, 4.0 mm stent: 81) RESOLUTE INTEGRITY Durable Circumferential Symmetrical ORSIRO Biodegradable Circumferential Asymmetrical ( 3.5 mm stents: 80) Coating thickness, μm / 3.5 (ab-/luminal) Coated strut thickness, μm (of smallest stent) Metal Platinum-chromium Cobalt-chromium Cobalt-chromium Polymer PLGA (poly [lacticco-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 silicon carbide (probio ) Drug Everolimus Zotarolimus Sirolimus Drug release time, mo Degradation time, mo < 24

7 BIO-RESORT: Trial Design 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. 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 Everolimus-eluting SYNERGY Zotarolimus-eluting RESOLUTE INTEGRITY Sirolimus-eluting ORSIRO 30 days 1 year 2 years 3 years 4 years 5 years 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 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. 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 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.

8 Patients & Lesions Patients Synergy n = 1,172 Resolute Integrity n = 1,173 Orsiro 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 PCI Any 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 procedures Synergy n = 1,532 lesions Resolute Integrity n = 1,580 lesions Orsiro n = 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 %

9 Results: Target Vessel Failure Lancet 2016; 388: year follow-up

10 Results: Target Vessel Failure

11 Results: TVF Components Cardiac death at 2 year At 2-year follow-up, there was no statistically significant difference between DES groups in the components of target vessel failure (TVF) Target vessel myocardial infarction at 2 year Target vessel revascularisation at 2 year

12 Results: Target Lesion Failure 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

13 Results: TLR 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

14 Results: Stent Thrombosis Definite-or-probable stent thrombosis at 2-year follow-up Definite-or-probable stent thrombosis rates were low and similar among groups

15 Why is this study important? Reliable outcome data of contemporary DES in all-comers are of significant interest, particularly considering the use of different biodegradable DES with dissimilar polymers and degradation times. 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 Orsiro sirolimus-eluting stent might reduce the risk of repeat revascularisation after the first year of follow-up.

16 Summary & Conclusions Very thin-strut biodegradable polymers DES with flexible designs and refined coatings promote 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. Conclusion The combination of very thin strut stents with biodegradable polymers 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 reduce the risk of repeat revascularisation after the first year of follow-up. Further long-term data will be of great interest.

17 Trial Organization Steering Committee C. von Birgelen, MD PhD (Study PI) P. Danse, MD PhD M. Hartmann, MD PhD K. van Houwelingen, MD J. Louwerenburg, MD F. de Man, MD PhD M. Scholte, MD C. Schotborgh, MD M. Stoel, MD PhD Study Centers and Local PIs Thoraxcentrum Twente, Enschede C. von Birgelen, MD PhD Rijnstate Hospital, Arnhem P. Danse, MD PhD Haga Hospital, Den Haag C. Schotborgh, MD Albert Schweitzer Hospital, Dordrecht M. Scholte, MD BIO-RESORT Study Coordination CRE, Enschede M. Kok, MD G. Zocca, MD R. Buiten, MD L. van der Heijden, MD, PhD K. Tandjung, MD PhD Data Management, Analysis and Follow-up CRE, Enschede Monitoring and Organization of Clinical Event Adjudication Diagram, Zwolle Statistical Analysis M. Kok, MD G. Zocca, MD L. van der Heijden, MD, PhD C. Doggen, PhD (Statistical supervisor) Kok M.M. et al. EuroIntervention 2018; in press simultaneously online published (2-year follow-up) von Birgelen C. et al. Lancet 2016; 388: (1-year follow-up) The investigator-initiated randomized BIO-RESORT trial was equally funded by Biotronik, Boston Scientific and Medtronic.

18 Manuscript with further details is free available on the homepage of EuroIntervention DOI: /EIJ-D 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, MD 1*, Paolo Zocca, MD 1*, Rosaly A. Buiten, MD 1, Peter W. Danse, MD PhD 2, Carl E. Schotborgh, MD 3, Martijn Scholte, MD 4, Marc Hartmann, MD PhD 1, Martin G. Stoel, MD PhD 1, K. Gert van Houwelingen, MD 1, Gerard C.M. Linssen, MD PhD 5, Carine J.M. Doggen, PhD 6, Clemens von Birgelen, MD PhD 1,6 1 Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands 2 Department of Cardiology, Rijnstate Hospital, Arnhem, the Netherlands 3 Department of Cardiology, Haga Hospital, The Hague, the Netherlands 4 Department of Cardiology, Albert Schweitzer Hospital, Dordrecht, the Netherlands 5 Department of Cardiology, Hospital Group Twente, Almelo and Hengelo, the Netherlands 6 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.

19 Summary & Conclusions Very thin-strut biodegradable polymers DES with flexible designs and refined coatings promote 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 biodegradable polymers 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 reduce the risk of repeat revascularisation after the first year of follow-up. Further long-term data will be of great interest.