Carotid Stenosis
Known natural ...
Pooled ACAS/ACST data (Cochrane review, June 2005)
proven benefit of CEA for asymptomatic stenosis in men
Significant percentage of patients
CAS With and Without Protection CAS
Distal Protection
Distal protection device placed to distal
straight segment
Available off the shelf
CaRESS Secondary Endpoints SAPPHIRE
SAPPHIRE: 3 Year Data SAPPHIRE: 3 Year Data
CREST: RPCT in Low Risk Pts Multicenter pro...
CREST Is the Best Designed RPCT
However CRE...
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Preventing Stroke in Carotid Stenosis

Published on: Mar 4, 2016
Published in: Health & Medicine      

Transcripts - Preventing Stroke in Carotid Stenosis

  • 1. Carotid Stenosis Known natural history despite best medical tx Preventing stroke in Carotid Only surgical disease w/ proven tx (multiple RCT’s) Stenosis: Stenting or Question: not whether to treat, but how to treat Endarterectomy? symptomatic versus asymptomatic high-risk versus low-risk CEA versus CAS Symptomatic RCT’s: Best Med Tx ± CEA NASCET Pooled NASCET/ECST data (Stroke 2004;35:2855) 2,885 pts w/ TIA or minor stroke within 120 days 70-99%: 17% ARR (65% RRR) / 2 yrs Both studies demonstrate remarkably similar benefit of 50-69%: 6.5% ARR (29% RRR) / 5 yrs intervention <50%: no benefit Risk of recurrent stroke in symptomatic stenosis is early → ECST (reanalysis by NASCET criteria, Lancet 2003;34:514) treatment is NOT elective! 3,024 pts w/ TIA, retinal infarction, or non-disabling stroke Women lose most from delayed treatment within 6 months 70-99%: 21.2% ARR / 5 yrs 50-69%: 5.7% ARR / 5 yrs <50%: no benefit (harm if <30%) Asymptomatic RCT’s: Best Med Tx ± CEA ACAS (JAMA 1995;273:1421) 1,662 pts w/ angio or validated doppler > 60% 5.9% ARR (53% RRR) / 5 yrs required low surgical M&M (1.5%) no stat. sig. benefit for women ACST (Lancet 2004;363:1491) 3120pts w/ doppler > 60% stenosis 5.4% ARR (11.8→6.4% risk) / 5 yrs results more robust than ACAS surgical M&M more realistic (3.0%) 50-69% 70-99% Pooled NASCET, ECST subgroup analysis… Stroke 2004,35(12):2855 1
  • 2. Pooled ACAS/ACST data (Cochrane review, June 2005) proven benefit of CEA for asymptomatic stenosis in men women, elderly benefit to a lesser degree CEA for asymptomatic stenosis Cochrane Review, June 2, 2005 ARR for stroke or death: Symp. vs Asymp. (<68, <75) NASCET/ECST symptomatic 70-99% ~ 8.5% per year ACAS/ACST asymptomatic >60% ~ 1% per year Caveats: 1. Symptomatic benefit is chiefly upfront: first several months 2. Asymptomatic benefit is long-term: ~ 2 yrs for curve crossover Questions: 1. How does this CEA data relate to decision-making regarding CAS (real world, high-risk pts, peri-op M&M + risk of MI…)? 2. Would decreased periprocedural M&M of CAS permit further gains in risk reduction, across more subgroups?? CEA for asymptomatic stenosis Cochrane Review, June 2, 2005 High Risk Patients…excluded a priori High Risk Patients…found post hoc ACAS Exclusions NASCET Exclusions Previous stroke Age older than 79 years; Previous CEA Previous ipsilateral endarterectomy; Previous EC-IC bypass Intracranial stenosis more severe than the surgically accessible NASCET Surgical risks (30 day periop M&M): High risk because of associated lesion medical illness Lung, liver, or renal failure Long-term anticoagulation therapy Lack of angiographic depiction of both Intolerance of aspirin or long-term carotid arteries and their symptomatic ≥ 70% 5.8% total = 3.7% minor aspirin therapy at a high dose intracranial branches. stroke, 1.5% major stroke, Life expectancy <5 years Uncontrolled hypertension or diabetes Surgically inaccessible lesion Unstable angina pectoris 0.6% death Myocardial infarction within the previous 6 months Contralateral carotid endarterectomy symptomatic ≥ 70% AND 14.3% total within the previous 4 months Progressive neurologic dysfunction contralateral occlusion A major surgical procedure within the previous 30 days. 2
  • 3. Significant percentage of patients NASCET / ACAS / ACST with carotid stenosis are at high surgical risk or have one or more CEA reduces stroke risk in Selected exclusion criteria Patients Bottom Line Message… Increasing data over the past In low risk pts the risk of stroke and death from CEA must be decade shows CAS is better Less than 7% for symptomatic patients Less than 3.5% for asymptomatic patients for these patients Early randomized trials of CAS Embolic Events The biggest problem with CAS First randomized trial of CEA vs. CAS halted due to high rate of complications in stented pts Naylor et al. 1998 Despite advances in stent technology and antithrombotic/antiplatelet regimens, significant Embolic Stroke complication rate in stent trials remained 7-10% in late 1990’s Lack of Technology, Experience, Embolic Protection When do most embolic events occur? Distal embolic protection devices Angioplasty Plaque fracture Debris release Stent + Post Dilatation Plaque strainer Debris release Cheese Grater effect In all CAS FDA studies with emboilc protection Embolic Stroke visible debris was collected in over 50 % of cases 3
  • 4. CAS With and Without Protection CAS a systematic review Complications Kastrup et al Stroke 2003 (N=1222) Without With Protection Protection without DEP with DEP TIAs 8.1% 2.6 Minor Stroke 2.1% 1.3 Minor stroke 94/2537(3.7) 5/896(0.5) Major Stroke 1.1% 0.3 Major stroke 28/2537(1.1) 3/896(0.3) 30-day Mortality 0.5% 0 Death 8/2537(0.3) 8/896(0.8) Death & Stroke 3.8% 1.6 Any stroke or death 140/2537(5.5) 16/896(1.7) Mathias & Schwarz CAS: DWI and clinical outcome +/- DPD Embolic Protection Kastrup et al, Stroke 2006;37:2312 Three Types Filtration Must completely fill the vessel and have a high capture efficiency Maintenance of distal flow Distal Occlusion with a balloon Flow arrest must be tolerated/atraumatic Particle washout/aspiration Flow Reversal Must tolerate hemodynamics of flow reversal Challenges with second generation device need to be overcome Concept ECA ICA Distal Protection Devices Overview Filter Occlusion Filter Devices AccuNet (Guidant) FilterWire (EPI-BSC) NeuroShield/Cardio- Shield (MedNova) E.Trap (Metamorphics) The Trap VFS (MicroVena) Sentinel (BSC/SciMed) Spider Distal Occlusion Devices CCA PercuSurge (Medtronic) Triactive Kensey Nash Reversal 4
  • 5. Distal Protection Distal protection device placed to distal straight segment Available off the shelf EPI Filterwire- Applicable to most (>95%) of lesions Accunet Emboshield Percusurge Small ICA (<3mm) Acute carotid occlusions - to prevent embolization of large column of clot that might overwhelm a filter device Study devices only Spider – Most deliverable (for difficult lesions) but filter has larger pores Angioguard MAE One Year Rate Trends in High Risk CAS Trials Carotid Revascularization Using Endartectomy or Stenting Systems (CaRESS) 15.7% 16 Multicenter, prospective, non-randomized trial 14 comparing CAS (with DEP) and CEA 12 10.2% Symptomatic > 50% Asymptomatic > 75% 10 9.1% Choice of CEA vs. CAS up to treating physician 8.3% Primary endpoint 8 All-cause mortality at 30 days and 1 year 6 4.5% Secondary endpoints 4 Composite 30-day all-cause mortality or stroke: residual stenosis, restenosis, repeat angiography, 2 and carotid revascularization at 30 days and 1 year; 0 CABERNET CABERNET BEACH BEACH ARCHeRI 1 ARCHeR ARCHeR2 ARCHeR 2 SAPPHIRE SAPPHIRE* and quality of life changes at 1 year. *Registry Arm Results CaRESS Demographics CaRESS Primary Endpoints Variable CEA (n=254) CAS (n=143) P value Symptomatic 33% 31% NS Stent CEA P value Previous CEA 11% 30% < 0.01 (N=143) (N=254) Previous CAS 0% 6% < 0.01 Previous peripheral angioplasty 0.4% 2% NS 2.1% 3.6% NS Death/CVA @ 30 Contralateral stenosis 40% 34% NS days CAD or previous AMI 61% 66% NS Death/CVA @ 1 year 10.0% 13.6% NS CHF 17% 13% NS Death/CVA/MI @ 30 2.1% 4.4% NS HTN 81% 81% NS days Hypercholesterolemia 70% 64% NS Death/CVA/MI @ 1 10.9% 14.3% NS Diabetes 24% 29% NS year Peripheral vascular disease 41% 45% NS 5
  • 6. CaRESS Secondary Endpoints SAPPHIRE Randomized trial of CAS with DEP compared with CEA in a high-risk population Endpoint CAS CEA P value Symptomatic stenosis of at least 50% (N=143) (N=254) Asymptomatic stenosis of at least 80% Residual stenosis 0.9% 0.0% NS 747 enrolled: 334 underwent randomization Restenosis 6.3% 3.6% NS Repeat angiography 3.6% 2.1% NS Primary endpoints Composite of death, stroke, myocardial infarction Carotid revascularization 1.8% 1.0% NS within 30 days, or Death or ipsilateral stroke at 31 days and 1 year SAPPHIRE: 3 Year Data SAPPHIRE: initial results Endpoint CAS CEA P value (N=159) (N=151) Death 7.0% 12.9% 0.08 All Stroke 5.8% 7.7% 0.52 Major ipsilateral stroke 0% 3.5% 0.02 Myocardial infarction 2.5% 8.1% 0.03 Cranial nerve palsy 0 5.3% 0.003 Target vessel 5.1% 7.5% 0.40 revascularization MAE 12.0% 20.1% 0.05 Trends favor CAS SAPPHIRE: 3 Year Data SAPPHIRE: 3 Year Data 6
  • 7. SAPPHIRE: 3 Year Data SAPPHIRE: 3 Year Data ARCHeR Multicenter single arm trial evaluating CAS in high risk pts ARCHeR Results Update Combined primary endpoint of death, stroke, MI @ 1yr Guidant ACCUNETTM Filter OPC ie Historical ARCHeR 1 8.3% Control For CEA ARCHeR 2 10.2% = 14.5% ARCHeR 3 9.6% (JVS 2006;44:258) Event-free survival was 90.4% at 1 year and 88.4% at both 2 and 3 years. Target lesion revasc. was 2.2% and 2.9% @ 1 and 2 years respectively. Low-risk Trials Bottom line from recent data… Symptomatic: EVA-3S - symptomatic stenosis ≥ 60% ARCHeR - 30-day any stroke/death: 3.9% CEA, 9.6% CAS - halted after 527 patients recruited CaRESS - embolic protection not used initially, CAS operators relatively less experienced… SAPPHIRE Symptomatic: SPACE - symptomatic stenosis ≥ 70% - 1183 patients randomized to CAS vs CEA 1. CAS M&M appears slightly better than CEA - 30-day ipsilateral stroke/death: 6.84% CAS, 6.34% CEA (ns) - embolic protection used in only 27% 2. At 1 year, CAS is equally efficacious as CEA - failed to prove non-inferiority (halted, underpowered) Asymptomatic: ACT I - Randomization of CAS compared with CEA in low-risk patients …in HIGH RISK patients…! - 3 CAS to 1 CEA randomization - Ongoing 7
  • 8. CREST CREST: RPCT in Low Risk Pts Multicenter prospective randomized trial CAS vs. CEA Results from the Lead-in Phase Guidant ACCUNETTM Filter After ACST, eligibility in CREST expanded to involve asymptomatic pts > 60% Plans to enroll 2500 pts CREST CREST Lead Ins Multicenter prospective randomized trial CAS vs. CEA Symptomatics at 30 days Periprocedural stroke in 4 of the 81 Lead-In patients treated without EPD (4.9%) Periprocedural stroke in 12 of 332 with EPD (3.6%)* No significant difference by symptomatic status, co-morbidities, or timing of stroke 30 day combined M&M compared to NASCET * 1st generation Acunet was bulky and inflexable!! Study Patients Stenosis Stroke & Death CREST Lead-In Patients (AHA 2003) NASCET 328 >70% 5.8% 10.0% eriprocedural 8.0% 4.9% CREST 191 >50% 5.7% troke 6.0% 3.6% 4.0% S 2.0% P 0.0% Without With ACCUNET ACCUNET N=81 N=332 ^As of October 24, 2004 CREST Lead Ins CREST Asymptomatics at 30 days Continues to enroll patients (>700) 30 day combined M&M compared to ACAS CREST (lead-in) MAE Study Patients Stenosis Stroke & Death 191 Symptomatic patients – 5.7% 395 Asymptomatic patients – 3.5% ACAS 721 >60% 2.2% Asymptomatic patients now included CREST 395 >70% 3.5% Await conclusion of enrollment and global statistica ^As of October 25, 2004 analysis 8
  • 9. CREST Is the Best Designed RPCT Conclusions However CREST will take Years to complete 1. CEA remains gold standard, against which any new CREST is enrolling NASCET/ACAS type pts treatment must prove safety & efficacy not high risk patients 2. High-risk pts should be treated by CAS: proven To meet the need for high risk pts and FDA efficacy with less risk approval company sponsored registries have 3. Low-risk patients should undergo CEA OR be been performed enrolled in trials: CREST, CaRESS… 4. CAS and CEA can be complementary…the compleat clinical must have every technical arrow in his/her quiver 9

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