Intro & Latest Contemporary DES Data and Clinical Implications - - PowerPoint PPT Presentation

Intro & Latest Contemporary DES Data and Clinical Implications

Emmanouil S. Brilakis, MD, PhD Minneapolis Heart Institute

Biotronik SCAI satellite session Tuesday, May 21, 2019

6.30-6.45 pm

Disclosures

• Consulting/speaker honoraria: Abbott Vascular,

American Heart Association (associate editor Circulation), Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), CSI, Elsevier, GE Healthcare, InfraRedx, Medtronic

• Research support: Regeneron, Siemens
• Shareholder: MHI Ventures.
• Board of Trustees: Society of Cardiovascular

Angiography and Interventions

Orsiro Ultrathin Strut (BP SES) Stent System

*For 2.25mm to 3.0mm diameter stents, 80 µm for >3.0 mm diameter stents

Stent Material L-605 Cobalt-Chromium Strut thickness 60 µm* Polymer material Poly-L-lactic acid (PLLA) Polymer type Bioresorbable, asymmetric circumferential thickness Passive coating Amorphous silicon carbide Antiproliferative drug Sirolimus (1.4 µg/mm2), >80% eluted in first 90 days

* ø 3.0 mm diameter, when compared to key competitors. BIOTRONIK data on file.

• 1. Xience and Xience Sierra are registered trademarks of Abbott Cardiovascular Systems. 2. Resolute Onyx is a registered trademark of Medtronic.
• 3. Synergy is a registered trademark of Boston Scientific

Information on devices manufactured at companies other than BIOTRONIK was gathered from multiple sources. However, it has not been verified by the vendors and we cannot guarantee its accuracy.

Orsiro DES: The only Ultrathin DES in the United States*

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Durable Durable

Polymer coating Abbott Medtronic Xience Sierra1 CoCr-EES Resolute Onyx2 CoNi-ZES

Bioabsorbable

Boston Scientific BIOTRONIK Synergy3 PtCr-EES Orsiro CoCr-SES Thin Strut Drug-Eluting Stents Ultrathin Strut Drug-Eluting Stent

Bioabsorbable

proBIOTM

Source: BIOTRONIK data on file.

The Foundation of Orsiro is the Novel PRO-Kinetic Energy Stent Design

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▪ Strong Cobalt Chromium (CoCr) alloy ▪ Double helix stent design for a smooth outer contour and outstanding flexibility. ▪ 3 Longitudinal connectors designed to resist longitudinal compression.

• 1. BIOTRONIK Data on file

*Synergy is a registered trademark of Boston Scientific. Disclaimer: Information on devices manufactured at companies other than BIOTRONIK was gathered from multiple sources. However, it has not been verified by the vendors and we cannot guarantee its accuracy.

Double Helix Stent Design for a Smooth Outer Contour and Outstanding Flexibility1

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Smooth outer contour

Two helical meanders Excellent flexibility and smooth crimped profile Wedge shaped transitions Consistent scaffolding through entire stent Ring element Defined stent length Three longitudinal connectors per helix Designed to minimize foreshortening and resist longitudinal compression

Orsiro

Synergy Boston Scientific*

1. BIOTRONIK data on file. 2. Rzany A, Schaldach M. Smart Material Silicon Carbide: Reduced Activation of Cells and Proteins on a-SiC:H-coated Stainless Steel. Progress in Biomedical Research 2001; May: 182- 194

proBIOTM Passive Layer of Silicon Carbide

7 50.8 14.9 6.4 0.9 10 20 30 40 50 60

CoNi PtCr CoCr CoCr with proBIO

Mass of Nickel release per surface area [ng/cm2]

• 98%
• 94%
• 68%

Reduced nickel ion release compared to other stent platforms1

• Made of amorphous silicon carbide and is

responsible for the unique color of BIOTRONIK stents2

• Intended to improve surface

characteristics and reduce nickel ion release2

• In vitro studies have shown up to a 98%

reduction of nickel ion release when the stent surface is coated with silicon carbide.1

BIOTRONIK data on file. 1. Expansion to Nominal Pressure;

• 2. 3.0mm: Xience Sierra, 4.0mm: Xience Alpine, Xience is a registered trademark of Abbott Cardiovascular Systems.
• 3. Synergy is a registered trademark of Boston Scientific
• 4. Resolute Onyx is a registered trademark of Medtronic.

Visibility

[Left] Radiopacity of crimped stents [Right] Radiopacity of expanded stents1

ø3.0mm

ø4.0mm

from left to right – Orsiro, Xience2, Synergy3, Resolute Onyx4

Orsiro Orsiro Orsiro Orsiro

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No Compromise on Radial Strength5

Orsiro – Only Crossing Profile Under 1mm

*

*for selected diameters; **Xience Xpedition 1. Resolute Onyx is a registered trademark of Medtronic. 2. Synergy are registered trademarks of Boston Scientific. 3. Xience Sierra is a registered trademark of Abbott Cardiovascular Systems. 4. ø 3.0 mm diameter, when compared to key competitors. BIOTRONIK data on file. 5. ø 3.0 mm diameter, when compared to key competitors. BIOTRONIK data on file. 6. Compared to Xience Xpedition. 7. Expanded 3.0 mm diameter stents are radially compressed (15% of Ø) along full length. The force required to compress the stent is radial strength. BIOTRONIK data on file. Disclaimer: Information on devices manufactured at companies other than BIOTRONIK was gathered from multiple sources. However, it has not been verified by the vendors and we cannot guarantee its accuracy.

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Lowest crossing profile

• n the US market4

15% More radial strength6,7

Resolute Onyx Synergy Xience** Orsiro Resolute Onyx1 Synergy2 Xience Sierra3 Orsiro

0.90

Worldwide Orsiro Clinical Programs

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65 48k+ 70k+

Studies ongoing, including all-comers 48,500+ patients enrolled 70,000+ patients enrolled and planned

2011 2012 2013 2014 2015 2016 2017 2018 2018 2018 2019

Worldwide Orsiro Clinical Programs

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SORT OUT VII BIONYX SORT OUT IX BIOSTEMI ORIENT BIO-RESORT BIOSCIENCE All Comers Pivotal Superiority Design

USA Japan China Europe

2011 2012 2013 2014 2015 2016 2017 2018 2018 2018 2019

BIOFLOW V Trial Design

• 1,334 patients randomized between May

2015 and March 2016 ⎯ 884 Orsiro and 450 Xience

• Patients enrolled in 13 countries in North

America, Europe, Israel, Asia, and Australia and New Zealand

• Primary endpoint TLF at 1 year with

planned follow-up through 5 years

BIOFLOW-V N=1,334 2:1 Randomization 884 BP SES, 450 DP EES 1 & 6-month follow-up 1-year follow-up TLF Primary Endpoint 3, 4, 5-year follow-up

clinicaltrials.gov NCT02389946 Kandzari et al. Lancet 2017

2-year follow-up Pre-specified Analysis

Key Enrollment Criteria

Inclusion Criteria

• Age ≥ 18 years
• IHD, stable or unstable angina, or silent

ischemia

• ≤ 3 de novo target lesions in ≤ 2 native target

vessels (TV)

• RVD ≥ 2.25 mm and ≤ 4.0 mm
• LL ≤ 36 mm
• TIMI flow > 1
• Eligible for DAPT therapy (aspirin + P2Y12)
• Provided informed consent

Exclusion Criteria

• Recent (< 72 hours prior to procedure) STEMI or

hemodynamically unstable NSTEMI/ ACS patients

• Chronic total occlusions, bypass grafts
• Bifurcations with side branch > 2.0 mm
• In-stent restenosis or active stent thrombosis
• LVEF < 30%
• Prior PCI within 30 days (non-TV) or within 9

months (TV)

• Planned staged PCI post-procedure
• Renal impairment > 2.5 mg/dL or 221 µmol/L or

dialysis dependent

• Excessively tortuous/ angulated or severely

calcified (operator visual assessment)

Doros et al. Am Heart J. 2017;193:35-45

Patient Disposition

884 BP SES 450 DP EES 848 (95.9%) active at 2-Year Follow-up

(807 completed visits; 25 missed visits)

428 (95.1%) active at 2-Year Follow-up

(401 completed visits; 18 missed visits)

1,334 randomized

52 Discontinued study 13 Withdrew consent 12 Were lost to follow-up 11 Other 16 Deaths 31 Discontinued study 9 Withdrew consent 4 Were lost to follow-up 9 Other 9 Deaths

Clinical Characteristics BP SES (N=884) DP EES (N=450)

Age, years 64.5 ± 10.3 64.6 ± 10.7 Female 25.3% 27.1% Hypertension 79.7% 80.5% Hyperlipidemia 78.9% 82.4% Diabetes mellitus 34.0% 37.0% Prior MI 27.4% 25.9% Prior PCI 36.8% 33.0% Prior CABG 7.1% 5.2% Current smoking 23.6% 22.7% Clinical presentation Stable angina 48.4% 47.4% Acute coronary syndrome 51.4% 49.6%

Clinical Characteristics BP SES (N=1,051 Lesions) DP EES (N=561 Lesions)

Target lesion vessel Left anterior descending 41.0% 41.2% Left circumflex 26.5% 26.0% Right 32.4% 32.8% Reference vessel diameter (mm) 2.59±0.54 2.60±0.58 Lesion length (mm) 13.3±7.6 13.2±7.7 Bifurcation lesion 14.8% 15.0% Calcification, moderate/severe 24.0% 26.7% Vessel tortuosity, moderate/severe 58.8% 61.5% ACC/AHA Lesion Class B2/C 72.6% 75.9% Number of target lesions/patient* 1.2±0.4 1.3±0.5 Number of stents/patient* 1.3±0.7 1.5±0.9 Total study stent length/patient (mm)* 26.8±14.7 29.5±17.5 Patients with overlapping stents* 9.4% (83/884) 15.0% (67/448) Stent length/lesion 20.8±9.1 21.8±10.5

*P<0.05

BIOFLOW V

Primary Endpoint: Target Lesion Failure at 1 Year

8.92 5.92

Kandzari DE, et al. ESC 2017; Lancet 2017

BIOFLOW V

Target Lesion Failure at 2 Years

8.92 5.92

Orsiro BP SES (n=884) Xience DP EES (n=450) P value

Target lesion failure 7.5% 11.9% 0.015 Cardiac death 0.6% 0.5% 1.0 Target vessel MI 5.3% 9.5% 0.01 Ischemia-driven TLR 2.6% 4.9% 0.04 Cardiac Death/MI 7.0% 10.4% 0.047

All data represented as intention to treat

BIOFLOW V

2 Year Outcomes

BIOFLOW V

Target Vessel MI

BIOFLOW V

Landmark Analysis: Target Vessel MI

BIOFLOW V

Ischemia-Driven Target Lesion Revascularization Through 2 Years

BIOFLOW V

Landmark Analysis: Ischemia-Driven Target Lesion Revascularization

BIOFLOW V

Stent Thrombosis Through 2 Years

Stent Thrombosis Events BP SES (N=884) DP EES (N=450) P Value Definite 0.5% 1.2% 0.17 Probable

• Any ARC (Definite/Probable/Possible)

0.7% 1.5% 0.23 Definite/Probable Stent Thrombosis Early 0.3% 0.2% 1.00 Late (>30 days and 1 year) 0.1% 0.5% 0.26 Very late (> 1 year and 2 years) 0.5% 0.11 Late/Very Late (>30 days 2 years) 0.1% 1.0% 0.045

DAPT adherence at 2 years: 45.6% (368/807) BP SES; 45.1% (181/401) DP EES; P=0.88

BIOFLOW V

Target Lesion Failure at 2 Years by Subgroups

*Small vessels defined as 2.75 mm or smaller. † Non-overlapping vs. Overlapping stents subgroup analysis is only performed on subjects with lesion length > 26 mm.

• Through 2 years in the randomized BIOFLOW V trial, significant differences in TLF and target vessel MI
• bserved at 1 year were maintained in addition to emergence of other safety and efficacy differences that

favor an ultrathin strut BP SES over a contemporary generation thin strut DP EES ⎯ Lower TLF (7.5% vs 11.9%, P=0.015) ⎯ Lower target vessel related MI (5.3% vs 9.5%, P=0.01), both early (≤30 days) and late (31 days to 2 years) ⎯ Lower ischemia-driven TLR, driven by differences in late (>1 year) TLR (2.6% vs 4.9%, P=0.04) ⎯ Lower late/very late definite and definite/probable ST (0.1% vs 1.0%, P=0.045)

• These results not only advance a standard of comparison for new DES but also direct attention to strut

thickness and polymer composition as key features for iterative DES development

BIOFLOW V

Conclusions

Kandzari et al. JACC 2018

Health Economic Evaluation of the Two-Year Results After Implantation of an Ultrathin, Bioresorbable Polymer Sirolimus- Eluting Coronary Stent Compared to a Thin, Durable Polymer Everolimus-Eluting Stent

Soeren Mattke1, Mark Hanson1, Marc Bentele2

1University of Southern California, Los Angeles, CA; 2 BIOTRONIK AG, Buelach,

Switzerland

Methods

• Effect of events on cost and mortality based on published literature and expert input
• Cost CPI-adjusted to 2018 US$, future cost discounted by 3%

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• Markov simulation model to project mortality and cost outcomes
• U.S. health system perspective over 48-month horizon
• Univariate and probabilistic sensitivity analyses
• Event rates from BIOFLOW-V trial

Year 1 Year 2 ppMI TVMI TLR TVMI TLR BP SES 2.27% 0.48% 1.44% 0.49% 0.25% DP EES 4.45% 1.42% 1.42% 1.46% 1.47%

Note: Peri-procedural MI defined as elevation of CK-MB of >3x upper limit of normal. TLR rates exclude events in patients with concurrent TVMI. BP SES = bioresorbable polymer sirolimus-eluting stent; DP EES = durable polymer everolimus-eluting stent; ppMI = peri-procedural myocardial infarction; TLR = ischemic driven target lesion revascularization; TVMI = spontaneous target vessel-related myocardial infarction

Schematic model flow

23.05.2019

BP SES ppMI cost DP EES ppMI no-ppMI TVMI post-TVMI TLR post-TLR Death TVMI cost TLR cost Mortality

BP SES = bioresorbable polymer sirolimus-eluting stent; DP EES = durable polymer everolimus-eluting stent; ppMI = peri-procedural myocardial infarction; TLR = ischemic driven target lesion revascularization; TVMI = spontaneous target vessel-related myocardial infarction

$0 $1,000 $2,000 $3,000 year 1 year 2 year 3 year 4 Total ppMI $124 $0 $0 $0 $124 TVMI $561 $648 $198 $89 $1,496 TLR

• $10

$551 $142 $127 $810 2018 US$

Model predictions: Projected savings

23.05.2019

Total $675 $1,199 $340 $216 $2,429 5% 62% 33% Estimated savings per patient BP SES compared to DP EES

Note: Future cost discounted by 3%; BP SES = bioresorbable polymer sirolimus-eluting stent; DP EES = durable polymer everolimus-eluting stent; ppMI = peri- procedural myocardial infarction; TLR = ischemic driven target lesion revascularization; TVMI = spontaneous target vessel-related myocardial infarction

Patient Disposition

677 Patients in ACS Subgroup 454 Allocated to BP SES 223 Allocated to DP EES 426 Evaluable for primary endpoint 96.9% Follow-up 206 Evaluable for primary endpoint 96.9% Follow-up 1,334 Patients randomized

28 Did not complete a 12-month visit 14 Missed the 12-month visit 6 Withdrew consent 3 Were lost to follow-up 5 Died 17 Did not complete a 12-month visit 10 Missed the 12-month visit 2 Withdrew consent 2 Were lost to follow-up 3 Died

ACS Patient Clinical Characteristics

BP SES (N=454) DP EES (N=223)

Age, years 63.1±10.8 63.2±11.2 Female 25.8% (117/454) 29.6% (66/223) Hypertension 76.7% (342/446) 79.8% (174/218) Body mass index* (kg/m2) 29.2±5.5 28.4±4.9 Hyperlipidemia 76.1% (343/451) 82.5% (184/223) Diabetes mellitus 34.0% (154/453) 36.9% (82/222) Prior MI 28.7% (128/446) 26.2% (58/221) Prior PCI 29.0% (130/449) 25.8% (57/221) Prior CABG 6.9% (31/449) 5.0% (11/221) Current smoking 29.5% (134/454) 26.0% (58/223)

*P<0.05 for comparison

Procedural Outcomes

BP SES DP EES P value Lesion success* 99.6% (568/570) 99.7% (297/298) 0.967 Device success† 97.5% (556/570) 96.6% (288/298) 0.643 Procedure success‡ 94.7% (428/452) 89.7% (200/223) 0.023

*Lesion success defined as attainment of < 30% residual stenosis of the target lesion using any percutaneous method.

†Device success defined as attainment of < 30% residual stenosis of the target lesion using the assigned study stent only. ‡Procedure success defined as attainment of < 30% residual stenosis of the target lesion using the assigned study stent only

without occurrence of in-hospital major adverse cardiac events (MACE; composite of all-cause death, Q-wave or non-Q-wave MI, and any clinical-driven TLR).

12 Month TLF

5.4% 10.4%

12 Month TV-MI

3.3% 9.0%

Conclusions

• In the ACS subgroup population of the BIOFLOW V study, treatment with

BP SES compared with DP EES was associated with a significantly lower rate of 12-month TLF, a difference driven by significantly lower peri- procedural MI and spontaneous MI.

• These findings support treatment with an ultrathin strut BP SES in ACS

patients undergoing PCI.

• Simultaneous publication- Circulation: Cardiovascular Interventions

All Comers Trial; N=3,514 1:1:1 Randomization Orsiro: Resolute Integrity*: Synergy**

Landmark Analysis between 1 and 2 year follow-up1 Ultrathin Orsiro is the only modern DES to show statistically lower patient event rates compared to Durable Polymer DES.1

Ultrathin Orsiro Drug Eluting Stent vs Durable Polymer DES

• 1. Kok M et al. 2-year outcome of the 3-arm BIO-RESORT randomized trial in allcomer patients treated with contemporary DES. Presented at:

EuroPCR; May 23, 2018; Paris, France; ClinicalTrials.gov : NCT01674803 *Resolute Integrity is a registered trademark of Medtronic. **Synergy is a registered trademark of Boston Scientific.

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Orsiro BP SES (n=1,169) Resolute Integrity DP ZES (n=1,169) P value Target Lesion Failure (TLF) 1.1% 2.4% 0.02 Target Lesion Revascularization (TLR) 0.6% 1.5% 0.04

All Comers Trial Lower Target Lesion Failure (TLF) Between 1 and 2 years

1

TLF rate between 1 and 2 years

54%

Lower TLF rate

Landmark Analysis Between 1-2 Years: Lower TLF rate for patients treated with Orsiro1

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• 1. Kok M et al. 2-year outcome of the 3-arm BIO-RESORT randomized trial in allcomer patients treated with contemporary DES. Presented at:

EuroPCR; May 23, 2018; Paris, France; ClinicalTrials.gov : NCT01674803 *Synergy is a registered trademark of Boston Scientific. **Resolute Integrity is a registered trademark of Medtronic.

Log rank - P = 0.22, Difference 1-2 yrs -0.7 (-1.9-0.4) Log rank - P = 0.02, Difference 1-2 yrs -1.3 (-2.4- -0.2)

Synergy* Resolute Integrity** Orsiro

TLF1

Incidence of target lesion failure (%)

1.1%

TLF in 2nd year

Landmark Analysis Between 1-2 Years: Lower TLR rate for patients treated with Orsiro1

All Comers Trial Lower Target Lesion Revascularization (TLR) Between 1 and 2 years

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1

TLR rate between 1 and 2 years

60%

Lower TLR rate

• 1. Kok M et al. 2-year outcome of the 3-arm BIO-RESORT randomized trial in allcomer patients treated with contemporary DES. Presented at:

EuroPCR; May 23, 2018; Paris, France; ClinicalTrials.gov : NCT01674803 *Synergy is a registered trademark of Boston Scientific. **Resolute Integrity is a registered trademark of Medtronic.

TLR1

0.6%

TLR in 2nd year

Incidence of target lesion revascularization (%) Log rank - P = 0.18, Difference 1-2 yrs -0.6 (-1.5-0.3) Log rank - P = 0.04, Difference 1-2 yrs -0.9 (-1.7-0.0)

Synergy* Resolute Integrity** Orsiro

Orsiro:

• Thinnest strut DES available
• High deliverability
• Improved clinical outcomes

– Target vessel MI (early and late) – TLR (late) – Stent thrombosis (late and very late)

Conclusions