Carotid artery percutaneous treatment: back to the future Alberto Cremonesi MD, FESC

Transcription

1 Carotid artery percutaneous treatment: back to the future Alberto Cremonesi MD, FESC GVM Care & Research - Cardiovascular Department (Cotignola Italy)

2 Hypothesis: Does CAS present similar outcomes than CEA in a less invasive way?

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4 CAS Trend d MANE rate vs enrollment start and duration

5 Clinical Trials Evaluating CAS Treatment FDA Approval for High Risk Patients CAPTURE N = 4,225 ARCHeR N = 581 SECuRITY N = 305 EXACT N = 2,145 PROTECT N = 322 SAPPHIRE N = 747 CAPTURE 2 N = 6,361 High risk CHOICE N = 6,872 (enrolling) Standard risk SPACE (EU) N = 1,183 AHA Guidelines (pub.1995) EVA-3s (EU) N = 527 NASCET N = 2,885 ICSS (EU) N = 1,710 CREST N = 2,502 ACAS N = 828 ACT I N = 1, CEA CAS High Risk CAS Standard Risk

6 Meta-analysis of patients data from EVA3S, SPACE and ICSS

7 Although well published studies..very poor quality of the data!

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9 CREST: Study Overview Carotid Revascularization Endarterectomy vs. Stenting Trial Design Stent/EPD Prospective, Multicenter, Randomized 1:1 CEA to CAS RX Acculink / RX Accunet Superiority Hazard Ratio for CAS vs CEA with multi-year followup (NIH Analysis) Non-inferiority CAS is not worse than CEA at 1 year follow-up (FDA analysis) 1. Hypothesis First Lead-in patient 2000 Dec Lead-in Phase completed N=1, year follow-up completed Randomization Phase completed 2006 NIH Analysis Apr 2008 Jul Oct 2009 Feb 2010 Source: William W Gray. Reading the Tea Leaves: Possible Outcomes from the CREST Trial and Effects on the Field. TCT, San Francisco, CA; Lal BK, Brott TG. The Carotid Revascularization Endarterectomy vs. Stenting Trial completes randomization: Lessons learned and anticipated results. J Vasc Surg 2009; 50:

10 Primary Endpoint: Perioperative Components CAS CEA HR P-value Any Death, Stroke, or MI 5.2% 4.5% HR = 1.18; 95% CI: All Stroke 4.1% 2.3% HR = 1.79; 95% CI: Major Stroke 0.9% 0.7% HR = 1.35; 95% CI: MI 1.1% 2.3% HR = 0.5; 95% CI: The Primary Endpoint shows no inferiority for CAS vs CEA Significant differences in perioperative minor stroke and MI More MI s after CEA More minor strokes after CAS Both therapies showed a very low stroke rate Source: CREST Presentation at International Stroke Conference on February 26, 2010

11 The impact of CAS strategy on results No Stent Consistency + No EPD Consistency + Inexperienced CAS Operators = Poor CAS Results = Positive CAS Results ICSS, SPACE, EVA-3S EPD Mandatory + Credentialed CAS Operators CREST

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13 CEA CAS 2011 CAS

14 AHA recommendations

15 Recommendation for symptomatic carotid disease Class LOE Carotid stenosis 70-99%: CEA is recommended for the prevention of recurrent stroke I A Carotid stenosis 50-69%: CEA should be considered for recurrent stroke prevention, depending on patient-specific factors I B Carotid stenosis 70-99%: CAS IIb should be considered for high surgical risk patients, or may be considered as an alternative to CEA in high-volume centers with documented death and stroke rate < 6% B

16 CEA & CAS at clinical crossroad

17 Protected Carotid Stenting: Embolic Protection Systems

18 Patient tailored CAS The embolic load you may generate is absolutely unpredictable!!!

19 Proximal protected CAS outcomes A Meta-analysis of Proximal Occlusion Device Outcomes in Carotid Artery Stenting Robert M. Bersin, MD, MPH, FACC, FSCAI Medical Director, Endovascular Services Swedish Medical Center, Seattle, Washington R. Bersin et al, Catheterization and Cardiovascular Interventions, 2012

20 6 Study Databases (N=2,397) Database # Study and First Author Year Published Device N= ERCAS Registry (Stabile et al) MO.MA N=233 2 ARMOUR (Ansel et al) MO.MA N=262 3 Multi-center registry (Reimers et al) MO.MA N=157 4 Single-center registry in Italy (Stabile et al) MO.MA N= EMPIRE 2011 GORE N=475 (Clair et al)5 + FRS European Registry 2012 (Nikas et al)6 Analysis performed by Harvard Clinical Research Institute (Boston, MA) R. Bersin et al, Catheterization and Cardiovascular Interventions, 2012

21 Overall 30-day Event Rates R. Bersin et al, Catheterization and Cardiovascular Interventions, 2012

22 Total Stroke Rates by Age Group and Symptomatic Status 5% P value=0.67 5% Non-symptomatic 4% Symptomatic 4% 3% 2,59% 3% 2,01% 2% 1,46% 2% 1% 1,95% 0,56% 0,57% 1% 0% < R. Bersin et al, Catheterization and Cardiovascular Interventions, 2012

23 MCH Experience Proximal neuro-protection during CAS In-hospital to 30 day events Overall Asymptomatic Symptomatic Patients; n Any Stroke; n (%) Major Stroke; n (%) (1.0) (0.7) (2.3) 0 Minor Stroke; n (%) MI; n (%) Death; n (%) 4 (1.0) 1 (0.3) 0 2 (0.7) 1 (0.3) 0 2 (2.3) 0 0 A. Cremonesi et al. - Supplement EHJ, 2015

24 MCH Experience Proximal neuro-protection during CAS Gender difference 516 procedures of proximal protected CAS in 461 patients with symptomatic or asymptomatic carotid stenosis 70% Data Source and Independent Management ESREFO 24

25 30 Day Outcomes February 17, 2016, at NEJM.org

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27 ICSS No difference in the primary endpoint! N=1713, medium FU 4.2 y Brown MM. European Stroke Conference May 2012

28 February 17, 2016, at NEJM.org

29 This article was published on February 18, 2016, at NEJM.org. DOI: /NEJMoa

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31 Subgroup Analyses of the Primary Composite End Point and the End Point of Stroke or Death.

32 In conclusion, the long-term follow-up results of CREST did not show significant differences between carotid-artery stenting and carotid endarterectomy with respect to : o the primary composite end point of periprocedural stroke, myocardial infarction, or death o the post-procedural ipsilateral stroke over a time period that was appropriate for elderly asymptomatic and symptomatic patients o the long-term durability of stenting and endarterectomy to prevent stroke during the post-procedural period o the restenosis rate

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34 Stent and brain protection: CAS issues related to poor stent scaffolding Intra-strut plaque prolapse Post-procedural embolic events

35 The Challenge Lesion in the Carotid arteries are often anatomically and morphologically very challenging Vulnerable Plaque Stroke prevention by plaque coverage with a dedicated stent is indicated

36 IVUS Guided CAS PRECISE mm Plaque protrusion Courtesy Norihiko Shinozaki

37 Severe symptomatic LICA stenosis LEFT

38 OCT in Carotid Stenting Significant Plaque Prolapse

39 How to choose a correct stent?

40 Micro-mesh double layer carotid stents 40

41 Terumo Carotid Stent Radial force Roadsaver Stent Platform Design Double layer, micromesh Construction Braided mesh Material Nitinol Stent Delivery System Guide wire compatibility Introducer sheath compatibility Delivery system construction 0.014" (0.36mm) 5Fr. (I.D.> 0.074") Rapid Exchange (RX), RX segment length 25cm Plaque containment 41

42 RoadSaver Terumo Carotid Stent Scaffolding 42

43 RoadSaver Terumo Carotid Stent Scaffolding 43

44 RoadSaver Terumo Carotid Stent Scaffolding 44

45 RoadSaver Terumo Carotid Stent Scaffolding 45

46 Changing paradigms in CAS Micromesh stents and sustained anti-embolic action to reduce cerebral embolization may contribute to solve the remaining limitations of carotid stenting

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51 2016 RoadSaver All Comers Italian Registry - First results on 150 Patients Alberto Cremonesi MD, FESC Roberto Nerla MD

52 Clinical 30 days 30 days (n=150) MACCE (MI, stroke, death) 0 MI 0 Stroke 0 Death 0 Bilateral carotid disease (%) 31% Aortic Arch Type I, % 71% Type II, % 18% Type III, % 11% Bovine arch, % Target lesion severity, % 21% 80.8±7.5 Symptomatic lesion, % 29% Radial approach, % 7%

53 Optical coherence tomography N = 26 (17%) Plaque prolapse Any appreciable tissue prolapse among stent struts N=2 (7.7%) Strut malapposition Distance between stent strut and vessel wall > 200 µm N=0

54 Double Filtration During Carotid Artery Stenting First Experience with the PALADIN Carotid Post-Dilation Balloon with Integrated Embolic Protection

55 When Do Strokes Occur During Carotid Artery Stenting? % 30 The Vast Majority of the Risk of Stroke during the Stenting Procedure Occurs During 70% Post-Dilation 20 25% 10 5% 0 Access Stenting Post-Procedure

56 Why Do Minor Strokes Occur Despite EPD use? Distal Filter Wire EPD Pore Size ( microns) Filter Malapposition Improper Sizing Shape Mismatch Patient Movement Overwhelming Debris Burden External Carotid Artery Common Carotid Artery Stroke

57 Hypothesis Problem: o Risk of stroke is maximal during the post-dilation phase Solution: o Increase protection during the post-dilation phase

58 Double Filtration Technique Primary EPD 221 Non-consecutive Patients 2 Centers, Prospective, Non-Randomized Secondary EPD Double Filtration using a variety of primary filters and stents FilterWire used for all secondary filter 30 Day Neurological Death, Stroke, MI Post-Dilation Balloon

59 Double Filtration: Procedural and 30 day Results N=221 Number % 0 0% Stroke % Neurological Death 0 0% % Neurological Death 0 0% Stroke 0 0% % Procedural Events Myocardial Infarction 30-Day Events Myocardial Infarction Total Neurological Death/Stroke/MI

60 PALADIN Carotid Post-Dilation Balloon with Integrated Embolic Protection (IEP) Technology Filter Chassis Minimal Landing Zone Sheathless Design Filter Membrane with 40-Micron Pore Size Angioplasty Balloon First filter with ability to adjust size to suit patient anatomy

61 Capture Efficiency Testing Capture Efficiency % of Emboli Captured %of Emboli Captured Capture Efficiency Particle Size µm Data on file: Contego Medical LLC Particle Size µm

62 DW-MRI Evaluation: Preliminary Results DW-MRI Results Paladin (n=15) Incidence of New Lesions 13% # Lesions per patient 0.13 Mean Lesion Volume (cm3) 0.01 CARENET1 PROFI2 PROFI2 ICSS3 CGuard Proximal group Filter group Filter group (n=15) (n=26) (n=31) (n=31) (n=37) Incidence of New Lesions 13% 48% 45% 87% 73% Mean Lesion Volume (cm3) NA Comparative DW-MRI Results Across Studies Schofer. TCT 2014 JACC. April 2012 Lancet, March 2010 Paladin

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65 The problem: how best to treat the asymptomatic patient Can the commendably low rates of death and stroke during the CAS procedure in ACT I and CREST be translated into routine clinical practice, or can guidelines be changed to further liberalize indications for stenting, especially in asymptomatic patients? There is a major concern that the data from these two trials will be uncritically interpreted to mean that stenting is equivalent to endarterectomy and so further exacerbate the situation in Countries as U.S., where more than 90% of carotid-artery interventions are performed in asymptomatic patients. Data from both randomized trials and nonrandomized studies suggest that the annual rate of stroke among medically treated asymptomatic patients has declined over the past two decades, regardless of the severity of stenosis at baseline. Evidence now suggests that the annual rate of ipsilateral stroke may be as low as 0.5 to 1%, a rate that is very similar to that observed in ACT I and CREST after successful stenting or endarterectomy.

66 The solution: how best to treat the asymptomatic patient Outside clinical trials, endarterectomy and stenting should be reserved for patients with symptomatic severe stenosis or for asymptomatic patients who are shown to be at higher risk for stroke with medical therapy than with intervention. Such patients (approximately 10 to 15% of patients with asymptomatic stenosis of 70 to 99%) may be identified by an algorithm that incorporates information about micro-emboli detected by means of trans-cranial Doppler and in the future by imaging strategies that identify the vulnerable plaque.

67 CAS Back To The Future Protected carotid stenting is a mature alternative to CEA for ischemic stroke prevention. It should be reserved for patients with symptomatic severe stenosis or for asymptomatic patients who are shown to be at higher risk for stroke with medical therapy than with intervention. Some latest technical advancements may contribute to solve the remaining limitations of carotid stenting and to better understand the interaction stent/plaque Micro-mesh stent double-layer stent technology Balloon with integrated embolic protection Advanced intravascular imaging (OCT, OFDI, etc.)

68 Carotid stenting Protected CAS can be a primary choice treatment

69 Arguments to support extensive indication to carotid stenting? CAS for all plaques All plaques for all interventionalists Competence makes the difference! Complex but applicable Absolutely not applicable