Insights from the Magmaris Clinical Data: BIOSOLVE II and BIOSOLVE III 12 Month Follow Up

Transcription

1 Insights from the Magmaris Clinical Data: BIOSOLVE II and BIOSOLVE III 12 Month Follow Up Ron Waksman, MD FACC FSCAI FESC Professor of Medicine, Georgetown University Director, Cardiovascular Research Advanced Education MedStar Heart & Vascular Institute, Washington, DC

2 Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company Biotronik, Abbott Vascular, Boston Grant/Research Support Consulting Fees/Honoraria Major Stock Shareholder/Equity Scientific, Medtronic, Chiesi, Astra Zeneca, Infraredx, Cardinal Health. Company Names Amgen, Biotronik, Astra Zeneca, Boston Scientific, Medtronic, Pi Medical Med Alliance

3 Background DREAMS 2G second generation drug eluting bioresorbable magnesium scaffold was tested in the BIOSOLVE-II trial. The device underwent minor modifications in order to reduce the crossing profile to allow for 6F compatibility and withdrawal into the guiding catheter Based on the positive clinical and angiographic outcome of DREAMS 2G in BIOSOLVE-II the goal of BIOSOLVE-III was to confirm those outcomes on the modified product (now being called Magmaris) Moreover BIOSOLVE-III was intended to generate additional 12-month angiographic data, the time point when the device is fully resorbed

4 MAGMARIS Sirolimus Eluting MG Scaffold Sirolimus + PLLA (BIOlute) 15µm 15µm 9-Day Faxitron, porcine explant 6-crown 2-link design 15µm strut thickness 15µm strut width Optimized scaffold design for Higher bending flexibility Higher acute radial force Slower absorption rate: 95% at 12 months Sirolimus drug elution & PLLA (ORSIRO BIOlute coating) Tantalum radiopaque markers Gained CE mark in June 216

5 Study Design BIOSOLVE-II PRIMARY ENDPOINT BIOSOLVE-II: In-segment 6-month Prospective FIM enrolling 123 patients with de novo coronary artery stenosis BIOSOLVE-III Pivotal trial enrolling 61 patients with de novo coronary artery lesion BIOSOLVE-III: Procedure Success SECONDARY ENDPOINTS@1,6,12,24,36mo for the pooled BIOSOLVE-II&III data TLF* rate Cardiac death Target Vessel MI Clinically driven TLR Definite and probable scaffold thrombosis Coordinating Clinical Investigator M.Haude, MD, Lukaskrankenhaus GmbH, Neuss, Germany 1 month, Clinical FUP 6 month Clinical FUP (mandatory) Angiographic FUP (mandatory) IVUS / OCT (Subgroup only) Vasomotion (Subgroup only) 12 month Clinical FUP (mandatory) Angiographic FUP (voluntary) IVUS / OCT (voluntary) Vasomotion (voluntary) 2 year, Clinical FUP 1 month, Clinical FUP 6 month, Clinical FUP 12 month Clinical FUP (mandatory) Angiographic FUP (mandatory) 2 year, Clinical FUP CORELAB Cardialysis, Rotterdam, The Netherlands Medstar, Washington DC, USA 3 year Clinical FUP Angiographic FUP (voluntary) IVUS / OCT (voluntary) Vasomotion (voluntary) 3 year, Clinical FUP *Composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization and CABG

6 Inclusion/ Exclusion Criteria for both Biosolve II and Biosolve III studies. Exclusion Criteria* Inclusion Criteria* Maximum of two single de novo lesions in two separate coronary arteries Evidence of myocardial infarction within 72 hours prior to index procedure Target RVD by visual estimation, mm LVEF <3% Target lesio le gth y isual esti atio Thrombus in the target vessel (visualized by QCA) Target lesio ste osis y isual esti atio < 1% %- Severe calcification Patients with three-vessel disease, where all three vessels require treatment Previous CABG in the target vessel Additional coronary lesion in the same vessel, which requires treatment Totally occluded coronary artery (TIMI flow ) Target lesion involves a side branch (vessel diameter > 2. mm), a bifurcation or is located 5 mm next to a bifurcation Ostial lesions Unsuccessful pre-dilatation *Similiar inclusion/ exclusion criteria for both studies, list truncated

7 18 Investigational Sites in 9 countries in Europe, Brazil and Singapore Investigator Country M. Haude, MD (CCI) H. Ince, MD S. Kische, MD A. Abizaid, MD R.Tölg, MD P. Lemos, MD N. Van Mieghem C. von Birgelen, MD E. Christiansen, MD S. Verheye, MD M. Valgimigli, MD W. Wijns, MD F.J. Neumann, MD B. Witzenbichler, MD C. Kaiser, MD E. Eeckhout, MD S.T. Lim, MD J. Escaned, MD Germany Germany Germany Brasil Germany Brasil The Netherlands The Netherlands Denmark Belgium Switzerland Belgium Germany Germany Switzerland Switzerland Singapore Spain N N Biosolve-II Biosolve-III

8 Patient Flow 184 subjects BIOSOLVE-II, N= 123 BIOSOLVE-III, N= 61 N= 2 devices not implanted N= 1 missed visit N= 1 death N=1 cardiac death 1-month Follow-up (98.4%) 18 subjects 1 death N= 2 devices not implanted N= 1 missed visit N= 3 death 6-month evaluation (98.4% ) 178 subjects 3 death N= 2 cardiac death N= 1 non-cardiac death (cancer) N= 2 devices not implanted N= 2 missed visit N= 4 death 12-month evaluation (97.8%) 176 subjects 4 death N= 2 cardiac death N= 2 non-cardiac death (cancer, urosepsis and multi-organ failure) All clinical events are CEC adjudicated

9 Baseline Characteristics Baseline Characteristics Age (mean ± SD) BIOSOLVE-II (N=123) BIOSOLVE-III (N=61) N (%) N (%) Overall (N=184) N (%) 65.2 ± ± ± 1.8 Male 78 (63.4) 39 (63.9) 117 (63.6) Hypertension 11 (82.1) 45 (73.8) 146 (79.3) Hyperlipidemia 74 (6.2) 4 (65.6) 114 (62.) Smoking 67 (54.5) 35 (57.4) 12 (55.4) Diabetes mellitus 36 (29.3) 1 (16.4) 46 (25.) -Insulin dependent 11 (3.6) 1 (1.) 12 (26.1) -Non-Insulin dependent 25 (69.4) 9 (9.) 34 (73.9) History of MI 29 (23.6) 14 (23.) 43 (23.4) Previous percutaneous Intervention 52 (42.3) 24 (39.3) 76 (41.3)

10 Lesion Characteristics Lesion Location N=188 BIOSOLVE-II (N=123) BIOSOLVE-III (N=65) N (%) N (%) Overall (N=184) N(%) LAD 47 (38.2) 31 (48.4) 78 (41.7) LCx 29 (23.6) 16 (25.) 45 (24.1) RCA 45 (36.6) 16 (25.) 61 (32.6) 2 (1.6) 1 (1.6) 3 (1.6) Intermediate Branch Lesion Characteristics N=188 BIOSOLVE-II N (%) Lesion Length (mm ± SD) RVD (mm ± SD) AHA/ ACC Lesion Class B2/C* Calcification Moderate/Severe* BIOSOLVE-III N (%) Overall N(%) 12.6 ± ± ± ± ± ± (43.4) 52 (81.3) 15 (56.4) 13 (1.7) 15 (23.4) 28 (15.1) * Statistical Significant differences between BIOSOLVE-II and BIOSOLVE-III population

11 BIOSOLVE-II and III pooled Target Lesion Failure out to 12-month 6-month N=181 % N=18 % Cardia Death Target Vessel MI Clinically driven TLR CABG.... TLF Scaffold Thrombosis Definite or probable Composite 12-month of TLF: cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization and CABG All events have been adjudicated by a clinical event committee

12 Late Lumen Loss at 12-month Cumulative Frequency (%) Cumulative Frequency (%) N= ± ± In-Segment Late Lumen Loss (mm) In-Scaffold Late Lumen Loss (mm) 1.5

13 Cumulative Frequency (%) Cumulative Frequency (%) In-Segment Late Lumen Loss at 12-month BIOSOLVE-II vs BIOSOLVE-III 6.24 ± ± In-Segment Late Lumen Loss (mm) BIOSOLVE-II N= In-Segment Late Lumen Loss (mm) BIOSOLVE-III N=54 1.5

14 Cumulative Frequency (%) Cumulative Frequency (%) In-Scaffold Late Lumen Loss at 12-month BS-II vs BS-III 6.39 ± ± In-Scaffold Late Lumen Loss (mm) BIOSOLVE-II N= In-Scaffold Late Lumen Loss (mm) BIOSOLVE-III N=54 1.5

15 Case Example 57 years old male. No associated risks factors. No previous coronary interventions. Ischemic status at enrolment is stable angina, CCS Class II. Procedure: Lesion in Prox-LAD (Visual estimation: 14.7x2.8mm, Pre-procedure stenosis: 71%) Lau her EBU. F guidi g atheters a d Asahi Sio. guide ire. Pre-dilatation with a 3.x8mm Pantera (16atm) 3.x2mm DREAMS implanted with 14atm. Post-dilatation performed with a 3.5x8mm Pantera (18atm) Follow-up: 1M, 6M and 12M FU: ischemic status without pathological findings. Event: no event reported.

16 Angiography at Index Post-PCI PROJECTION A PROJECTION A Pre-PCI PANTERA 3. x 8 1 inflation, 16atm PANTERA 3.5 x 8 2 inflations, 18atm DREAMS #1 3. x 2

17 Angiography at Index BASELINE PROXIMAL REFERENCE Lumen Area: 9.86mm2 IN-SCAFFOLD MINIMUM LUMEN Stent Area: 7.15mm2 DISTAL REFERENCE Lumen Area: 7.28mm2

18 Notable OCT Frames DISSECTIONwith with CAVITY CAVITY DISSECTION DISSECTIONwith with CAVITY CAVITY DISSECTION ERODEDCAVITY CAVITY ERODED A B DISSECTION/Fissure DISSECTION/Fissure CIRCUMFERENTIAL ISA (A)DISSECTION (B)PROTRUSION

19 Angiography at Index and at 12 Month Post-PCI 12M F/U PROJECTION A PROJECTION A Pre-PCI In-stent LLL.41 mm In-segment LLL.41 mm

20 Angiography at Index and at 12 Month 12M-FU PROXIMAL REFERENCE IN-SCAFFOLD MINIMUM LUMEN Lumen Area: 9.86mm2 Stent Area: 7.15mm2 Lumen Area: 9.16mm2 Lumen Area: 4.85mm2 %RAS: Percentage Residual Area Stenosis DISTAL REFERENCE Lumen Area: 7.28mm2 Lumen Area: 8.4mm2

21 Magmaris vs. Orsiro: Flow diagram of the study. Biosolve II trial (n = 123) Biosolve III trial (n = 61) MAGMARIS Group ITT (n = 184) Excluded: lost follow-up 2 miss visit 3 death 2 No device implanted At 6 months (n = 177) ORSIRO Group ITT (n = 298) At 6 months (n = 286) Multivariate logistic regression analysis Legend: ITT = intention to treat. Bioflow II study (n = 452) Excluded: 3 lost follow-up 5 miss visit 2 death 2 withdrawal

22 Magmaris vs. Orsiro: Baseline and procedural characteristics Magmaris Group (n=184), ITT N % Orsiro Group p-value (n=298), ITT N % Baseline Characteristics Age, y (SD) 65.5± ±1.4.4 Age category.283 < 75 yrs yrs Male gender Cardiac risk factors Diabetes mellitus Hypertension Hypercholesterolemia History of smoking History of myocardial infarction History of previous coronary intervention Ischemic status Unstable Angina ACC/AHA lesion characterization Type A <.1 Type B Type B <.1 Type C Procedural Characteristics 13.± ± Lesion length, mm (Mean ± SD) 2.8± ± Reference vessel diameter, mm (Mean ± SD) 54.1± ±14.2 <.1 Pre procedure DS(% ± SD) Legend: ACC = American College of cardiology; AHA = American Heart Association; DS = diameter stenosis; ITT = intention to treat; SD = side deviation. Similar Baseline Characteristics Between Orsiro and Magmaris

23 Magmaris vs. Orsiro: Clinical outcomes at 6 months (unadjusted) Magmaris Group Orsiro Group (n=184), ITT N % (n=298), ITT N % p-value Events at 6 months, n (%) Death Cardiac death MI* TVMI Clinically driven TLR Any TLR Clinically driven TVR Any TVR Death and MI Cardiac Death or MI Target-lesion failure Target-vessel failure Death, MI, or any revascularization Definite ST.... Probable ST Legend: ITT = intention to treat; MI = myocardial infarction; ST = stent thrombosis; TLR = target lesion revascularization; TVMI = Target Vessel Myocardial Infarction; TVR = target vessel revascularization. * 212 MI universal definition. Multivariate adjusted showed that device type was not independent predictor of clinical events

24 Conclusion TLF (3.3%) and TLR (1.7%) rates in BIOSOLVE-II and III remain low and comparable to 2nd generation drug-eluting stents out to 12-month There was no definite or probable scaffold thrombosis up to 12-month In-segment and in-scaffold late lumen loss where.25 ±.31 mm and.39 ±.34 mm and comparable to previous results for DREAMS 2G The case example demonstrates angiographically an open lumen at 12month and restoration of the original curvature after degradation of the scaffold The 12-month OCT demonstrates the resorption of the device and a homogeneous endothelialization and completion of the healing process Overall the data generated in Biosolve II was validated in Biosolve III suggesting consistency of good performance of the technology In selection of patients and lesions Magmaris performs similar to Orsiro

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