State of the Art Management of Carotid Stenosis Mark R. Harrigan, MD UAB Stroke Center Professor of Neurosurgery, Neurology, and Radiology University of Alabama, Birmingham Disclosures NIH funding for clinical trials Consultant for Scientia Vascular and Medtronic 1
Carotid Stenosis Accounts for ~20% of ischemic strokes Carotid endarterectomy: Has been around since 1953 Carotid stenting: < 20 years Don t forget the importance of medical management Asymptomatic Carotid Stenosis Common in Western countries: A carotid atherosclerotic plaque is present in 31% of general population J Vasc Surg 1988, 8:674-8 Two major trials of surgery versus medical therapy for asymptomatic stenosis ACAS (Asymptomatic Carotid Atherosclerosis Study) 1,662 patients JAMA 1995;273:1421-8 ACST (Asymptomatic Carotid Surgery Trial) 3,120 patients Lancet 2004;363:1491-502 Both trials showed similar results: Risk of stroke with asymptomatic carotid stenosis >60% is about 2% per year Surgery offers a slim advantage over medical therapy 2
Asymptomatic Carotid Stenosis Recent data suggests that the risk of asymptomatic stenosis has fallen significantly since the 1980s Stroke 2009;40:e573-83 Studies in the last decade have found annual ipsilateral stroke rates of 1.3% Eur J Vasc Endovasc Surg 2005;30:275-84 1.2% Stroke 2005;36:1128-33 0.6% Stroke 2007;38:1470-5 Oxford Vascular Study Stroke 2010;41:e11-7 Population-based study, the only study to include patients only since the year 2000 Average annual rate of ipsilateral stroke was 0.34% Factors that raise risk of stroke with asymptomatic stenosis Rapid progression of stenosis Progression of asymptomatic stenosis: observed in 24.7% of 523 patients undergoing serial carotid Duplex exams (annual rate: 7%). Among these patients: Annual risk of ipsilateral stroke: 7.7% Stroke 2013;44:792-4 Microemboli on transcranial Doppler Embolic signals on TCD are present in ~10% of patients with asymptomatic stenosis Stroke 2005;36:2373-8 Annual risk of stroke in asymptomatic patients with embolic signals: 8% Lancet Neurol 2010;9:663-71 More risk factors for stroke Atherosclerotic plaque features: Total plaque burden JAMA Neurol 2015;72:1261-7 Enhancement of the carotid bulb adventitia on CTA Stroke 2013;44:3344-9 Volume of plaque ulceration on 3-dimensional ultrasound Stroke 2014;45:1437-41 Plaque echolucency on ultrasound Stroke 2015;46:91-7 Motion of intraplaque contents on B-mode ultrasonography J Neurosurg 2012;117:574-8 COATed platelet level of 45% Platelets 2014;25:93-6 Silent embolic infarction on CT or MRI. Annual risk of stroke in asymptomatic patients with imaging evidence of stroke: 3.5% J Vasc Surg 2009;49:902-9 3
New concept: Aggressive medical management SAMMPRIS (Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis) Multicenter randomized trial of patients with symptomatic intracranial stenosis Patients were randomized to either: Aggressive medical therapy or Aggressive medical therapy + Angioplasty and stenting SAMMPRIS Results 30-day stroke and death rate Stenting plus medical therapy: 14.7% Medical therapy alone: 5.8% (p=0.002) N Engl J Med 2011;365:993-1003 4
SAMMPRIS Medical Management Target systolic blood pressure <140 mm Hg (<130 mm Hg in patients with diabetes) Target LDL cholesterol <70 mg/dl Once LDL is <70 mg/dl, target non-hdl cholesterol <100 mg/dl and triglycerides <200 mg/dl For diabetics, target hemoglobin A1c <7% Smoking cessation Target body mass index (BMI) <25 kg/m 2 if initial BMI is 25-27 kg/m 2 or 10% weight loss if initial BMI is >27 kg/m 2. Moderate intensity exercise at least 3 times per week for 30 minutes per session Lifestyle coaching J Stroke Cerebrovasc Dis 2011;20:357-68 The surgeon s role in medical management Traditional conception is that medical management is beneath surgeons Obsolete! Surgeon can be a sledgehammer to drive home the importance of medical management with patients and their primary care physicians Not detailed medical management The surgeon mystique can be used to influence patient behavior CREST 2 Carotid revascularization and medical management for asymptomatic carotid stenosis Primary aim: In patients with 70% asymptomatic stenosis, assess differences between medical management and CEA or CAS Aggressive medical management is identical to SAMMPRIS 5
CREST-2 Parallel Study Design (n = 1,240 in each trial) S = Screened R = Randomized CREST 2 Enrollment so far: 664 of 2,480 UAB: 6 Currently the best possible management of asymptomatic carotid stenosis is to participate in CREST 2 Symptomatic carotid stenosis NASCET (North American Symptomatic Carotid Endarterectomy Trial) 2,885 patients with symptoms in previous 120 days with 30-99% stenosis randomized to medical therapy (risk factor reduction and aspirin 1300 mg daily) Stroke rate at 2 years ( 70% stenosis) Medical group: 26% Surgical group: 9% N Engl J Med 1991;325:445-53 6
CEA or CAS? CREST Carotid Revascularization Endarterectomy vs. Stent Trial Multi-center trial of stenting versus surgery in both symptomatic and asymptomatic carotid patients Total randomized patients: 2,522 Symptomatic: 1,326 Asymptomatic: 1,196 CREST Results Primary endpoint: Stroke, myocardial infarction, or death within 30 days of enrollment or any ipsilateral stroke within 4 years N Engl J Med 2010;363:11-23 Median follow-up: 2.5 years Primary composite endpoint rate was not different between the groups: 7.2% in stenting group 6.8% in the surgery group (p=0.51) During the 30 day periprocedural period: Higher rate of stroke in the stenting group: 4.1% in the stenting group 2.3% in the surgery group (p=0.01) Higher rate of myocardial infarction in the surgery group: 1.1% in the stenting group 2.3% in the surgery group (p=0.03) 7
CREST Results: Symptomatics 30-day stroke and death rate Symptomatic patients: 6.0% in the stenting group 3.2% in the surgery group (p=0.02) N Engl J Med 2010;363:11-23 CREST: Effect of Age Younger patients did better with stenting, and older patients did better with surgery N Engl J Med 2010;363:11-23 European Trials: Stenting versus Surgery SPACE (Stent-Supported Percutaneous Angioplasty of the Carotid versus Endarterectomy) 1,214 patients EVA-3S (Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis) 527 patients ICSS (International Carotid Stenting Study) 1,713 patients Result: No difference between surgery and stenting at 2 years Lancet Neurology 2008;7:893-902 Result: Higher rate of stroke and death at 4 years with stenting Lancet Neurology 2008;7:885-92 Result: Higher rate of stroke, death and MI at 120 days with stenting Lancet 2010;375:985-97 8
CEA vs CAS? Presently, Medicare favors CEA for most patients and will reimburse for CAS only if the patient is high-risk for CEA or is enrolled in a clinical study Contralateral occlusion Previous radiation to the neck Symptomatic restenosis after CEA Congestive heart failure Class 3 or 4 Surgically inaccessible lesion Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) Vascular surgeons do 93% of the CEAs in the U.S. SVS-VQI is an enormous 300-center registry with data on 10s of thousands of CEAs and CAS procedures Example. Analysis of 4,587 CEAs. Rate of reoperation for bleeding: With protamine 0.7% Without protamine 1.2% (P<0.01) CEA: Nuances Timing of surgery: Sooner is better than later, but not too soon Trend toward earlier CEA Stroke 2017;48:225-8 2005: Average 25 days till surgery 2013: Average 6 days till surgery Risk of complications are not elevated with CEA within 7-15 days of symptoms Stroke 2015;46:3423-36 Increased risk with CEA <2 days after symptoms Stroke 2012;43:1331-5 9
More nuances Awake or asleep? The European GALA (General Anesthesia vs Local Anesthesia) trial randomized 3,526 CEA patients to general anesthesia or local anesthesia. 48 Primary outcome: stroke, or death. Lancet 2008;372:2132-42 General anesthesia primary outcome: 4.8% Local anesthesia primary outcome: 4.5% Patch or no patch? Systematic review of 10 trials: Cochrane Database Syst Rev 2009:CD000160 Lower risk of post-op stroke (p=0.001) Lower risk of long-term stroke (p=0.001) Lower risk of occlusion and restenosis (p<0.00001) One more nuance Stroke immediately after CEA Traditional teaching: reopen and explore Stroke after CEA: Go to the angio suite first 10
CAS: Nuances Most CAS procedures are straighforward The key: Avoid risky cases CAS risky cases Comprehensive Stroke Center designation Joint Commission Certification ~200 CSCs in the U.S. Requirement: Report CEA and CAS results 11
Carotid Endarterectomy and Stenting at UAB FY 2016 40 35 30 27 25 20 15 13 14 10 10 5 2 3 6 7 0 Sx CEA Asx CEA Sx CAS Asx CAS Total: 52 CEA procedures, 30 CAS procedures = 82 total Neurosurgery Vascular Surgery Aggregate 30-day Stroke and Death FY15 FY16 50 45 40 35 30 25 20 15 10 5 0 35 43 40 30 29 25 23 20 Total Cases 17 Stroke & Death 18 15 13 9 10 5 2 1 1 0 0 0 1 0 0 Sx CEA Asx Sx CAS Asx Sx CEA Asx CEA Sx CAS Asx CAS CEA CAS 4.6% 2.5% 5.5% 0% 0% 0% 5.8% 0% Total Cases Stroke & Death Conclusions Management of carotid disease has become extremely sophisticated in recent years Large amount of good data to base decision-making on Patient care should be highly individualized 12