Medtronic Symposium The Complex Bifurcation Patient: new insights into stent selection

Transcription

1 Medtronic Symposium The Complex Bifurcation Patient: new insights into stent selection Carlo Trani, MD, FESC Cardiology Department, Catholic University of the Sacred Heart, Rome - Italy

2 How would you treat this?

3 OPTIMIZED PROVISIONAL (POT, distal rewiring and final kissing)

4 OPTIMIZED PROVISIONAL (POT, distal rewiring and final kissing)

5 OPTIMIZED PROVISIONAL (POT, distal rewiring and final kissing) Courtesy by Mortier (EBC 2009)

6 How can we study procedural differences? Pre-Clinical Approach Visible Heart Lab Collaboration with the University of Minnesota unique to Medtronic General Procedures Include: Cardioplegia, removal, cannulation, Langendorff perfusion / 4 chamber modes, visualization of devices

7 OPTIMIZED PROVISIONAL (distal rewiring and final kissing) Simulation of distal rewiring and kissing (Burzotta, Visible Heart Lab, Minneapolis)

8 DOES STENT DESIGN IMPACT OUTCOMES IN BIFURCATION STENTING? Do performance differences exist? Do platform advantages translate into procedural advantages? Ultimately, what does the clinical data show? Stent Design Parameter Strut design: shape, thickness Cell size, perimeter Overexpansion capability Conformability Procedural Outcome Sidebranch access Apposition Long-Term Performance Efficacy and safety TLR, TVMI, ST

9 Stent Design: Strut Shape Influence on crossing into the Side Branch For many stent designs, complex irregular cell shape may obstruct wire or catheter advancement through the side of the strut 1 Square struts Round struts Images shown are not to scale and are only for illustrative purposes. Catheter tips are shown around an 8-mm bend radius. 1 Carrié, TCT Mediterranean 2012

10 Z-SEASIDE Clinical Data Burzotta, EBC 2011

11 Response to SB Dilation (KB) Stent Design: Expandable Cell Size Resolute Integrity TM DES Test Setup Xience Prime TM DES Cell Size After Expansion 3.0-mm Stent Design Diameter (mm) Resolute Integrity DES 3.84 Resolute (Driver) DES 3.70 Xience Prime DES 3.80 Promus Element DES 3.48 Promus Element TM DES Bench test data on file at Medtronic, Inc. Testing performed on BMS equivalent of each DES. Cell area expanded with a 4.0-mm balloon n = 2 deployed to RBP. These tests may not be indicative of clinical performance.

12 SB SCAFFOLDING ANALYSES SB SCAFFOLDING LENGTH ASSESSED BY VIRTUAL SIMULATION vs IN VITRO QCA MEASURES C IN VITRO SCAFFOLDING LENGHT (mm) SIMULATED SCAFFOLDING (mm) Cypher Select Taxus Libertè Endeavor Resolute Xience V A B Burzotta F, Mortier P, Trani C, Submitted

13 STENT OVEREXPANSION FOR CONFORMABILTY IN THE MAIN VESSEL Bench testing*: 3.5mm stent dilation with 7x20 mm balloon *Burzotta, Trani (personal data)

14 STENT OVEREXPANSION FOR CONFORMABILTY IN THE MAIN VESSEL Bench testing*: 3.0mm stent dilation with 6x20 mm balloon 5.879mm 5.879mm *Burzotta, Trani (personal data)

15 STENT OVEREXPANSION EFFECT OF POT

16 Mortier ahead of publication Apposition Study FEA Apposition Testing Measurement of stent struts distance from vessel wall after FKB Integrity Bifurcation Model B FEA Multi-Link 8 Omega (Element) Percentage of stent struts greater than 100um from vessel wall Computer Simulation Integrity Multi-Link 8 Omega (Element) p-value Int vs. ML8 p-value Int vs. Omega Bifurcation A 3.1±0.3% 5.4±0.5% 6.4±2.2% Bifurcation B 4.3±0.9% 9.3±1.1% 14.1±1.4% Bifurcation C 3.10±0.2% 5.5±0.7% 5.8±0.9% Total per stent design 3.4±0.7% 6.6±2.0% 8.5±4.1% Mortier P, EBC 2012

17 Pre-Stent QCA PRE-CLINICAL OCT VALIDATION OF COMPUTER SIMUTLATION P-MB 3.85mm Post-Procedure OCT 3.8mm 2.8mm 2.5mm D-MB3.0mm SB - 2.6mm MB SB Integrity Platform Computer Simulation (n=18) Pre-Clinical Evaluation (n=3) Total malapposed struts per 3.8 ± 1.2% 2.8 ± 0.7% stent greater than 100µm 2 OCT analysis and reconstruction courtesy of N. Foin

18 Integrity Stent Platform The smooth round struts of Resolute allows for easy wire & balloon crossing access Open cell perimeter allows for large expandable cell size Stent overexpansion to 4.75mm (and more) for proximal sizing SUPERIOR stent strut apposition in bifurcated lesions Sinusoidal-formed wire Helical wrap Laser-fused

19 Resolute DES to Treat Bifurcations in the Real World RESOLUTE Pooled Bifurcation Subset N=703 Study was not powered or prespecified for the analysis shown. TLR is ischemia-driven.

20 Italian Registry Data Italian ClinicalService project: A national medical care project aimed at evaluating and improving the use of implantable cardiac devices in clinical practice Ongoing 14-center prospective registry on all-comers pts implanting at least 1 Resolute stent (2067 pts entered so far) Pts followed by phone contact at 1,6, 12, 24, 36 and 48 months to assess the occurrence of MACE (cardiac death, non-fatal myocardial infarction, TLR, TVR and ST defined according to the ARC criteria) ClinicalTrials.gov identifier: NCT

21 Italian Registry Data bifurcation substudy FU (months) Mean sd Median q1 q3 min max 577 patients

22 ANGIO CHARACTERISTICS Number of treated BIF 611 LM 10.6% LAD-Diag 52.6% LCx-OM 27.8% RCA 8.7% Medina % Medina % Medina % Medina % Medina % Medina % Medina % SIMPLE INTERMEDIATE COMPLEX

23 STENTING TECHNIQUE 5.5% Double stent 12% 2.3% 1.5% 1.1% Single stent 88% 0.5%

24 Italian Registry Data bifurcation substudy Mean sd Median q1 q3 min max 577 patients Event type All patients (577) MACE 47 (8.2%) Cardiac Death 12 (2.1%) IMA 22 (3.8%) TLR 27 (4.7%) TVR 33 (5.7%) ST 5 (0.9%) Overall death 26 (4.5%)

25 Freedom from MACE_Event (%) IMPACT OF PCI TECHNIQUE ON OUTCOME MACE Hazard Ratio [double vs single] Complexity Hazard Ratio 95% Hazard Ratio Confidence Limits p-value Complex Intermediate Easy Kaplan Meier MACE_Event survival estimate - Tecnica logrank P =.005 Simple Double Months since stent implant Number at risk Simple Double

26 IMPACT OF STENT DESIGN ON OUTCOME Patient Characteristics TOTAL (N = 652) RESOLUTE-INTEGRITY (N = 216) RESOLUTE (N = 436) p-value Medina Complexity. Complex 30.3% 25.9% 32.4% Intermediate 39.6% 43.1% 37.9%. Simple 30.1% 31.0%. Technique. Provisional stenting 80.1% 86.6% 76.8% TAP stenting 5.6% 2.8% 7.0%. T-stenting 1.6% 1.9% 1.4%. V-stenting 0.5% 0.5% 0.5%. Crush 1.1% 0.9% 1.2%. Coulotte 2.3% 1.4% 2.8%. Other 8.9% 6.0% 10.3%. Double stenting. Kissing Balloon 11.8% 7.6% 13.8% % 60.3% 66.6% 0.115

27 Freedom from TVR_Event (%) IMPACT OF STENT DESIGN ON OUTCOME Event type Stent Resolute (373) Resolute Integrity (194) MACE 35 (9.4%) 9 (4.6%) Cardiac Death 10 (2.7%) 2 (1.0%) AMI 15 (4.0%) 6 (3.1%) TLR 22 (5.9%) 3 (1.6%) TVR 27 (7.2%) 3 (1.6%) ST 5 (1.3%) 0 (0%) Overall Death 20 (5.4%) 6 (3.1%) Kaplan Meier TVR_Event survival estimate - Stent logrank P =.014 Resolute Resolute Integrity Months since stent implant Number at risk Resolute Resolute Integrity

28 Summary and Conclusions Simulated analysis of the Resolute Integrity stent platform resulted in significantly lower amount of malapposed struts in bifurcation models The Z-SEASIDE study showed that there can be procedural advantages when using the Resolute ZES over SES & EES in bifurcated lesions The 2 available large registries, the RESOLUTE pooled bifurcation and the Italian Clinical Service bifurcation datasets, show that in the real world Resolute ZES results in: High success rate of provisional stenting with single stent implantation Sustained clinical efficacy up to three years

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30 TM Mortier Apposition FEA Analysis Details Write footnote here Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan or France Medtronic, Inc. All rights reserved. UC bML 8/13

31 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 Stent Design Influences Apposition in Bifurcation Lesions Testing Set-up of Comparative Apposition Study 1 Stenting technique: 1. Stent deployment 3.0 mm x 18 mm Integrity TM BMS (Medtronic) 3.0 mm x 18 mm Multi-link 8 TM BMS (Abbott Vascular) 3.0 mm x 20 mm Omega TM BMS (Boston Scientific) 2. Proximal optimisation technique (POT) 4.0 mm or 4.5 mm x 12 mm balloon inflated at 14 atm 3. Final kissing inflation Simultaneous inflation and deflation (12 atm) Modified FKBD SB first (12 atm), the partial SB deflation (4 atm), MB inflation (12 atm) Balloon sized to the distal branch diameter Bifurcation models studied: TM 1 Mortier, combined from EBC 2012 and PCR These tests may not be indicative of clinical performance.

32 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 Stent Strut Apposition: Bifurcation Model A Finite Element Analysis Apposition Results Integrity TM Platform Multi-link 8 TM Platform Omega TM (Element TM ) Platform TM Mortier, EBC 2012

33 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 Stent Strut Apposition: Bifurcation Model B Finite Element Analysis Apposition Results Integrity TM Platform Multi-link 8 TM Platform Omega TM (Element TM ) Platform TM Mortier, EBC 2012

34 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 Stent Strut Apposition: Bifurcation Model C Finite Element Analysis Apposition Results Integrity TM Platform Multi-link 8 TM Platform Omega TM (Element TM ) Platform TM Mortier, EBC 2012

35 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 Stent Strut Apposition Results Finite Element Analysis Apposition Results 1 The Integrity TM stent platform resulted in a lower amount of malapposed struts in all three bifurcation models Bifurcation Bifurcation Model A B FEA Integrity Platform Multi-link 8 Platform Omega (Element TM ) Platform The table below gives the percentage of stent struts with strut-artery distance above 100 µm. FEA Study Integrity Platform (n=18) 2 Multi-link 8 Platform (n=18) Omega (Element) Platform (n=18) Bifurcation A 3.1±0.3% 5.4±0.5% 6.4±2.2% Bifurcation B 4.3±0.9% 9.3±1.1% 14.1±1.4% Bifurcation C 3.10±0.2% 5.5±0.7% 5.8±0.9% Total per design 3.8±1.2% 6.7±2.2% 8.5±4.4% p-value Integrity BMS vs. <0.001 <0.001 TM 1 Mortier, PCR These tests may not be indicative of clinical performance. 2 n = 18 simulations were conducted for each stent across the three bifurcation models. Both simultaneous and a modified kissing balloon deployment technique were simulated.

36 TM RESOLUTE Pooled Bifurcation Subset Additional details Write footnote here Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan or France Medtronic, Inc. All rights reserved. UC bML 8/13

37 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 RESOLUTE Pooled Bifurcation Patient and Lesion Characteristics Patient Baseline Characteristics (%) N = 703 Patients Age (yr) 63.9 ± 11.1 Male 79.4 Diabetes mellitus 27.0 Hypertension 69.0 Hyperlipidemia 64.3 Current smoker 24.0 Prior MI 27.6 Prior PCI 28.9 Prior CABG 6.5 Cardiac status: Unstable angina 23.9 Myocardial infarction (STEMI + NSTEMI) 31.3 Lesion Characteristics (%) LAD 64.9 LCX 33.4 RCA 22.0 Left main 6.4 B2/C 73.2 TM

38 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 RESOLUTE Pooled Bifurcation Medina Classification 1 (1,1,1) 29.4% (1,1,0) 8.4% (1,0,1) 3.7% (0,1,1) 7.1% (1,0,0) 4.1% (0,1,0) 9.1% (0,0,1) 3.0% TM 1 Medina classification only available in RESOLUTE All Comers (R-AC) trial; n = 296 lesions.

39 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 RESOLUTE Pooled Bifurcation High Percentage of Provisional Stenting Technique N = 703 Patients Number of lesions treated per patient 1.55 ± 0.78 Number of stents per patient 1.99 ± 1.20 Total stent length per patient (mm) ± Lesion length* (mm) ± Reference vessel diameter* (mm) 2.86 ± 0.53 Minimum lumen diameter* (mm) 0.62 ± 0.50 Sidebranch RVD* (R-Int only) (mm) 2.2 ± 0.6 Double guidewires (%) 63.8 Main vessel stented (%) 97.9 Sidebranch stenting (%) 19.0 Bifurcation technique Culotte (%) 5.6 Minicrush\crush (%) 24.5 T (%) 39.2 Simultaneous kissing stent (%) 7.7 V (%) 9.8 Other (%) 13.3 Kissing balloon postdilatation (R-Int only) (%) 77.4 TM *For RESOLUTE International (R-Int), angiographic measurements are site reported.

40 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 RESOLUTE Pooled Bifurcation Acute Success Rates % N = 703 Patients Lesion success (the attainment of <50% residual stenosis of the target lesion using any percutaneous method) 99.6 Device success (the attainment of <50% residual stenosis of the target lesion using only the assigned device) 94.7 Procedure success (the attainment of <50% residual stenosis of the target lesion and no in-hospital MACE) 94.0 TM

41 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 RESOLUTE Pooled Bifurcation Clinical Outcomes at One, Two and Three Years % 1 Year n = Years n = Years n = 686 Death (all) Cardiac death Target vessel MI Q-wave Non-Q-wave Cardiac death or target vessel MI ARC def/prob ST (all) Early ( 30 days) Late ( days) Very late (>360 days) TLR TVR TLF (cardiac death, target vessel MI, TLR) TVF (cardiac death, target vessel MI, TVR) MACE (death, MI, TLR, emergent CABG) TM These subsets were not powered or prespecified.

42 Cumulative Incidence of TLR (%) Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 Powerful Performance Regardless of Bifurcation Technique No TLR Difference Between Provisional and Two-Stent Techniques RESOLUTE Pooled Analysis Bifurcation Subset, 3-Year Results Provisional One Stent Implanted (N=540) Two-Stent Techniques (N=163) p = Time After Initial Procedure (days) TM TLR is ischemia-driven. Study was not powered or pre-specified for the analysis shown.

43 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 RESOLUTE Pooled Bifurcation Clinical Outcomes by Number of Stents at Three Years % Provisional One Stent Implanted n = 540 Two-Stent Techniques n = 163 p-value Death (all) Cardiac death MI (target vessel) Q-wave Non-Q-wave Cardiac death + target vessel MI ST def/prob (all) Early ( 30 days) Late ( days) Very late (>360) TLR TVR TLF (cardiac death, TVMI, TLR) TVF (cardiac death, TVMI, TVR) MACE (death, MI, TLR, emergent CABG) TM These subsets were not powered or prespecified. p-value is adjusted to propensity score.

44 Trademarks may be registered and are the property of their respective owners. For distribution only in markets where the Resolute Integrity TM coronary stent has been approved for bifurcation lesions. Not for distribution in the USA, Japan, or France Medtronic, Inc. All rights reserved. UC bML 8/13 STENT CONFORMABILTY INTO THE MAIN VESSEL Bench testing*: 3.5mm stent dilation with 7x20 mm balloon 8 MAX diameter (mm) Cypher Xience Endeavor Resolute Taxus *Burzotta, Trani (unpublished data) TM

45 Resolute In Bifurcation Lesions Conclusions to date Simulated analysis of the Resolute stent platform resulted in significantly lower amount of malapposed struts in bifurcation models. The Z-SEASIDE study showed that there can be procedural advantages gained when using the Resolute ZES over SES & EES. In the RESOLUTE pooled bifurcation dataset we observed: Sustainable clinical efficacy out to two years, with very low rates of TLR (6.1%).

46 Summary and Conclusions Simulated analysis of the Resolute Integrity stent platform resulted in significantly lower amount of malapposed struts in bifurcation models. The Z-SEASIDE study showed that there can be procedural advantages gained when using the Resolute ZES over SES & EES. In the RESOLUTE pooled bifurcation dataset we observed: Sustainable clinical efficacy out to three years, with low rates of TLR. Our large Italian multicenter registry confirms the excellent performance of the Resolute DES in bifurcations: High rate of provisional stenting with single stent implantation Remarkable clinical efficacy out to a mean time of 27 months, with low rates of MACE (8.2%) and TVR (5.7%).

47 Stent Design: Side Cell Expansion Resolute Integrity TM stent s round struts facilitate wire access and balloon and stent crossing into a side branch Maximum cell perimeter allows you to address a wide range of side branch diameters and angulations Resolute Integrity TM DES Xience Prime TM DES Cell Size after Expansion 3.0mm Stent Design Diameter mm Resolute Integrity DES 3.84 Xience Prime DES 3.80 Promus Element DES mm Test Set-up Promus Element TM DES Bench test data on file at Medtronic, Inc. Testing performed on BMS equivalent of each DES. Cell Area expanded with a 4.0mm balloon n=1. These tests may not be indicative of clinical performance. Trademarks may be registered and are the property of their respective owners.

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50 How can we study procedural differences? Pre-Clinical Approach, Angioscopy Dr. Louvard will be showing this slide and video, you may not want to repeat it

51 CLINICAL SERVICE Italian Registry Data bifurcation substudy FU (months) Mean sd Median q1 q3 min max 577 patients Baseline characteristics 577 pazienti Male 448 (77.6%) Age 66.2 ± 10.7 Diabetes 163 (28.9%) Smoker 121 (21.2%) Hypertension 447 (77.8%) Hyperlipidemia 349 (61.9%) Clinical presentation ACS 265 (46.0%) ACS STEMI 70 (26.4%) Stable Angina 216 (37.5%) Silent Ischemia 95 (16.5%) CKD 63 (10.9%) LVEF (31.6%) <30 11 (2.4%) > (65.9%)

52 ANGIO CHARACTERISTICS Number of treated BIF 611 LM 10.6% LAD-Diag 52.6% LCx-OM 27.8% RCA 8.7% Medina % Medina % Medina % Medina % Medina 101 Medina % 21.9% Medina % BIFURCATION COMPLEXITY SIMPLE INTERMEDIATE COMPLEX

53 CLINICAL SERVICE Italian Registry Data Italian ClinicalService project: A national medical care project aimed at evaluating and improving the use of implantable cardiac devices in clinical practice The project consists of a shared environment for the collection, management, analysis and reporting of data from patients wearing Medtronic implantable devices An independent physician steering committee prospectively identifies key clinical questions on a yearly basis for analysis and publication A charter assigns the ownership of data to the centers and governs the conduct and relationship of the steering committee and Medtronic ClinicalTrials.gov identifier: NCT

54 CLINICAL SERVICE Italian Registry Data Ongoing Italian 14-center prospective registry on all-comers pts implanting at least 1 Resolute stent (2067 pts entered so far) Each patient signs an informed consent form, approved by the Institutional Review Board of each center Baseline assessment comprises the collection of demographic data and medical history, clinical examination, 12-lead electrocardiogram, estimation of NYHA functional class and angiographic data Procedural data are collected at the time of PCI Pts are followed by phone contact at 1,6, 12, 24, 36 and 48 months to assess the occurrence of major adverse cardiac events (MACE; cardiac death, nonfatal myocardial infarction, TLR, TVR and ST defined according to the ARC criteria)

55 Double stent rate (%) IMPACT OF LESION COMPLEXITY ON PCI TECHNIQUE 23.3% 10.7% 4.9%

56 DOES STENT DESIGN IMPACT OUTCOMES IN BIFURCATION STENTING? Do performance differences exist? Do platform advantages translate into procedural advantages? Ultimately, what does the clinical data show? Stent Design Parameter Procedural Outcome Long-Term Performance Strut design: shape, thickness Cell size, perimeter Overexpansion capability Conformability Sidebranch access Apposition Efficacy and safety TLR, TVMI, ST