Early healing after treatment of coronary lesions by everolimus, or biolimus eluting bioresorbable polymer stents

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1 Early healing after treatment of coronary lesions by everolimus, or biolimus eluting bioresorbable polymer stents One-month results of the study Ida Riise Balleby 1, Trine Krejberg Ørhøj 1, Christian Juhl Terkelsen 1, Lisette Okkels Jensen 2, Michael Maeng 1, Lars Romer Krusell 1, Jouke Dijkstra 3, Lisbeth Antonsen 2, Anne Kaltoft 1, Steen Dalby Kristensen 1, Mikkel Hougaard 2, Hans Erik Bøtker 1, Jens Flensted Lassen 1, Evald Høj Christiansen 1, Niels Ramsing Holm 1 1 Department of Cardiology, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark 2 Department of Cardiology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark 3 Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands

2 Potential conflicts of interest Speaker's name: Ida Riise Balleby I have the following potential conflicts of interest to report: Travelgrants: ABBOTT VASCULAR, MEDTRONIC, ST. JUDE MEDICAL

3 Background Improved early healing may reduce the risk of stent thrombosis in patients treated by DES Biomatrix DES (Biosensors) has shown excellent long term clinical outcome 1 Synergy DES (Boston Scientific) is designed to facilitate early healing and has shown promising clinical outcome 2 1 Serruys PW, et al. Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimuseluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) randomized, noninferiority trial. JACC Cardiovasc Interv Aug;6(8): Kereiakes DJ Efficacy and safety of a novel bioabsorbable polymer-coated, everolimus-eluting coronary stent: the EVOLVE II Randomized Trial Circ Cardiovasc Interv Apr;8(4)

4 Objective: One-month healing Synergy Biodegradable polymer Absorption time: 4 months ~ Everolimus eluting vs. Biomatrix Biodegradable polymer Absorption time: 6-9 months Biolimus A9 eluting 74 µm 120 µm Boston Scientific, USA Biosensors, Schwitzerland

5 Patient population Inclusion criteria 18 years of age or older Indications: SAP, UAP, NSTEMI, STEMI Exclusion criteria Life expectancy less than one year Unacceptable risk by 12-month dual antiplatelet treatment Creatinine >120 mmol/l Severe vessel tortuosity Allergy to aspirin, clopidogrel, ticagrelor, sirolimus, or biolimus Unable to provide written informed consent

6 Methods Dual-center study Randomization 1:1 - stratification for STEMI and diabetes OCT at baseline and at 1-month follow-up Clinicaltrials identifier: NCT Matched OCT analysis: QCU-CMS, LUMC, Leiden, NL

7 Primary endpoint at one month Coronary Stent Healing Index Healing index component Score 1) Uncovered struts (% of all strut counts pr lesion) >2%=1, >5%=2, >10%=3, >15%=4, >20%=5, >25%=6, >30%=7, >35%=8 >40%=9 2) Uncovered jailing struts and uncovered acquired or persisting malapposed struts (% of all strut counts pr lesion) >10%=1, >20%=2, >30%=3, >40%=4, >50%=5 ect. 3) Persisting malapposition (score for cummulated strut length pr lesion) 4) Acquired malapposition (score for cummulated strut length pr lesion) 5) Maximum neointimal thickness (score pr neointimal thickness interval) >1mm=1, 2mm=2 3mm=3 >1mm=1, 2mm=4, 3mm=6 >200µm=1, >300µm=2, >400µm=3 or diameter stenosis>50%=4, >75%=5 6) Cumulated extra stent lumen enlargement (score pr area interval) 0.2mm 2 =1, 0.4 mm 2 =2, 0.6mm 2 =3, 0.8 mm 2 =4, 1.0 mm 2 =5, 1.2 mm 2 =6

8 Primary endpoint at one month Coronary Stent Healing Index Healing index component Score 1) Uncovered struts (% of all strut counts pr lesion) >2%=1, >5%=2, >10%=3, >15%=4, >20%=5, >25%=6, >30%=7, >35%=8 >40%=9 2) Uncovered jailing struts and uncovered acquired or persisting malapposed struts (% of all strut counts pr lesion) >10%=1, >20%=2, >30%=3, >40%=4, >50%=5 ect. 3) Persisting malapposition (score for cummulated strut length pr lesion) 4) Acquired malapposition (score for cummulated strut length pr lesion) 5) Maximum neointimal thickness (score pr neointimal thickness interval) >1mm=1, 2mm=2 3mm=3 >1mm=1, 2mm=4, 3mm=6 >200µm=1, >300µm=2, >400µm=3 or diameter stenosis>50%=4, >75%=5 6) Cumulated extra stent lumen enlargement (score pr area interval) 0.2mm 2 =1, 0.4 mm 2 =2, 0.6mm 2 =3, 0.8 mm 2 =4, 1.0 mm 2 =5, 1.2 mm 2 =6

9 Power calculation Estimates for the individual components of the Coronary Stent Healing Index Coronary Stent Healing Index Synergy Biomatrix Uncovered stent struts 4 8 Uncovered jailing and malapposed struts 7 7 Persisting malapposition 1 2 Acquired malapposition 4 4 Neointimal thickness 2 2 Cummulated extra stent lumen enlargement 0 0 Total (lower value indicates improved healing) Estimates derived by historical data. Assumptions were α=0.05, power=0.90. Normal distribution assumed with estimated population SD=5 and SD=7 for Synergy and Biomatrix respectively. Sample size estimate: n=32 in both groups Planned inclusion of 40 patients in each group

10 Patient flow chart Patients in n=80 Excluded n=7 Synergy n=38 Biomatrix n=42 Excluded n=6 Withdrawal=5 Poor image quality=1 No baseline OCT=1 Withdrawal n=4 Failed to appear n=2 Events n=0 Events n=3 Cardiac death n=2 Stent thrombosis n =1 1-month FU Synergy in analysis n=31 Biomatrix in analysis n=33

11 Patient characteristics Synergy n=31 Biomatrix n=33 P-value Age (years) 63.4± ± Male gender 24 (77.4%) 26 (78.8%) 0.90 BMI (kg/m 2 ) 27.4± ± Diabetes 4 (12.9%) 4 (12.2%) 0.61 Creatinine (mmol/l) 78.7± ± Antihypertensive treatment 17 (56.7%) 16 (50.0%) 0.60 Statin treatment 11(36.7%) 15(53.1%) 0.42 Systolic blood pressure (mmhg) 138.3± ± Diastolic blood pressure (mmhg) 79.6± ± Previous PCI 2 (6.6%) 3 (9.1%) 0.53 Previous CABG LVEF, % 55.3± ± Indications for PCI: SAP UAP Non-STEMI STEMI 13 (41.9%) 1 (3.2%) 7 (22.6%) 10 (32.5%) 14 (42.4%) 0 (0%) 10 (30.3%) 9 (27.3%) 0.58

12 Procedural characteristics Synergy n=31 Biomatrix n=33 P-value Reference diameter (mm) 3.5± ± Number of stents (n) 1.2± ± Stent length (mm) 23.6± ± Max. balloon diameter (mm) 3.6± ± Max. balloon pressure (mmhg) 17.2± ±

13 One-month clinical endpoints Synergy n=38 Biomatrix n=42 Cardiac death 0 2* Stent thrombosis 0 1 TLR 0 1 Myocardial infarction 0 1 MACE 0 3** (7.1%) Same patient * Both cardiac deaths were STEMI patients with out-of-hospital sudden death **No follow-up OCT performed

14 Cumulated healing index score Primary endpoint at one month Coronary Stent Healing Index Worse healing Better healing 5 0 Synergy Biomatrix median [IQR] 10[6;12] 16[5.5;18] p=0.16

15 Coverage % Secondary endpoint Strut coverage at one month Full strut coverage 100 Lesion level Worse Synergy Biomatrix Coverage %, median [IQR] 72.2% [56.9;96.5] 64.3% [55.5;77.2] p=0.09

16 Coverage % Secondary endpoint Strut coverage at one month Lesion level Full strut coverage % 6% >95% coverage % 67% <75% coverage 60 Worse % 18% <50% coverage 30 Synergy Biomatrix Coverage %, median [IQR] 72.2% [56.9;96.5] 64.3% [55.5;77.2] p=0.09

17 Secondary endpoint Clustered malapposition* Synergy Biomatrix Malapposed at baseline 12 8 Baseline 1-month FU Abolished 8(66.7%) 4(50.0%) Persisting 4(33.3%) 4(50.0%) Acquired 1(8.3%) 0 *minimum 10 malapposed strut counts within 5 adjacent frames (0.65mm)

18 Secondary endpoint Minimal lumen area 7,5 7,3 7,1 mm 2 6,9 6,7 6,5 6,3 6.3 mm 2 P-value mm 2 Synergy Biomatrix 6,1 5,9 5,7 5,5 5,3 Synergy Biomatrix

19 µm Secondary endpoint Average neointimal thickness* 75 Lesion level p = µm µm Synergy Biomatrix *Neointimal thickness measured as the shortest distance from strut surface to lumen boarder

20 Conclusion No statistical difference was detected in one-month Coronary Stent Healing Index between Synergy and Biomatrix DES Synergy DES showed a trend towards better early strut coverage compared to Biomatrix DES Wide inter-patient variation in early healing was prominent in both stent groups The study