ISCHEMIC STROKE & TIA main etiologies

Transcription

1 דופלקס עורקי צוואר - משמעות בגיל הקשיש דר' יונתן שטרייפלר מנהל היחידה הנוירולוגית מרכז רפואי רבין - בי"ח השרון

2 תאריך בדיקה

3 ISCHEMIC STROKE & TIA main etiologies Large vessel (artery) disease - atherothromboembolism Cardiac source of embolism Small vessel (artery) disease

4 LARGE ARTERY DISEASE pathophysiology of ischemic insults Thrombo-embolism originating from an atheromatous, ulcerated plaque Thrombosis in situ at the site of the stenosed (by plaques) artery leading to occlusion Critical diminishing blood flow distal to a severely stenosed artery

5 CT Angiography Carotid occlusion Carotid stenosis + ulcer

6 Carotid endarterectomy

7 Kaplan-Meier survival curves showing probability of surviving severe symptomatic carotid stenosis in NASCET (1991) Barnett, H. J.M. Stroke 2009;40:e53-e65

8 Kaplan-Meier survival curves to show survival free of major stroke in surgery and control patients with 80 99% stenosis in ECST (1991) (non-stroke deaths occurring more than 30 days after surgery censored) ECST collaborators, Lancet 1998;351:

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10 Risk factors associated with symptomatic carotid stenosis Severity of the stenosis Time of symptoms Hemispheric TIA s (vs. retinal TIA s) Intracranial stenosis, No collateral circulation Contralateral carotid occlusion Plaque ulceration Presence of leukoaraiosis

11 5 year risk Rothwell P. M. (based on ECST) Lancet 2005;365:256-65

12 CAROTID STENTS & PROTECTIVE DEVICES

13 ICSS interim: meta- analysis CEA vs. stent Lancet 2.10

14 CREST - Primary End Point*, According to Treatment Group Symptomatic & asymptomatic Pts. * Stroke + periprocedural MI & death Brott T et al. N Engl J Med 2010; /NEJMoa

15 ICSS long-term outcome Courtesy of Prof. Martin Brown, UCL & Queen Square, London U.K.

16 Conclusions Carotid endarterectomy remains the treatment of choice for symptomatic carotid stenosis Rates of long-term stroke are low after both treatments ICSS results, ESC Lisbon 5.12

17 Cumulative Proportions of Patients with the Primary Composite End Point, Stroke or Death, and Any Stroke, According to Treatment Group. CREST (Symptomatic & asymptomatic Pts.) - long term follow-up Brott TG et al. N Engl J Med 2016.

18 הצרות קרוטידית אסימפטומטית Asymptomatic significant (>50%) carotid stenosis (ASCS) - גישה טיפולית

19 Prevalence of ASCS ( 50% stenosis) 4.2% in total 9.3% in people 70 years de Weerd, M. et al. Stroke 2009;40:

20 ASCS estimated annual risks of vascular events Stroke 2% Coronary events 7% Stroke mortality 0.6% Overall mortality 4-7%

21 ACAS: Carotid endarterectomy in asymptomatic men p= NS p= patients with an asymptomatic carotid stenosis 60 %. randomized to medical therapy with aspirin or CEA. mean follow up 2.2 years. Executive Committee for the Asymptomatic Carotid Atherosclerosis Trial. JAMA 1995; 273:1421.

22 ACST Asymptomatic Carotid Surgery Trial results Any type of stroke or perioperative death P< Fatal or disabling stroke or perioperative death P= ACST collaborators, Lancet 2004;363:

23 ACST 10 years follow up Of 3120 patients: % have died - 90% non stroke death Risk of stroke and peri-operative (PO) death: - Immediate surgery 13.4% - Deferred surgery 17.9% Peri-operative complications: Stroke, MI or death 3.2% Disabling stroke or death 1.7% Sept. 2008

24 Meta-analysis of ipsilateral stroke (including any stroke within 30 days) in RCTs and NRCSs of CEA versus medical therapy. Annual ipsilateral stroke risk on medical therapy = 1.68% Raman G, et al Ann Intern Med. 2013;158(9):

25 Temporal changes in the annual ipsilateral stroke risk in patients with ASCS treated medically. Naylor AR, Bell PRF, Semin Vasc Surg 2008;21:100-7

26 Use of medical treatments in the ACST study The use of lipid lowering drugs rose from 17 to 58% in last randomization period. Patient numbers reflect year of randomization. ACST collaborators, Lancet 2004;363:

27 Pleiotropic effect of statins on the vasculature DeGraba, T. J. Stroke 2004;35: Statins therapy was shown to arrest/ regress carotid atherosclerosis progression in randomized controlled trials Kang S. et al, Atherosclerosis 2004;177:433-42

28 Guidelines

29 Patients with high risk of stroke, i.e. men with stenosis of more than 80% and a life expectancy of more than 5 years, may derive some benefit from surgery in appropriate centers, i.e. peri-operative complications of less than 3% Chambers & Donnan, Cochrane Database 2005

30 Carotid endarterectomy--an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. For asymptomatic patients with 60 to 99% stenosis, the benefit/risk ratio is smaller compared to symptomatic patients and individual decisions must be made. Endarterectomy can reduce the future stroke rate if the perioperative stroke/death rate is kept low (<3%). Neurology Sep 27;65(6):

31 ESVS guidelines. Invasive treatment for carotid stenosis: indications, techniques, CEA is (also) recommended in asymptomatic men <75 years old with 70-99% stenosis if the perioperative stroke/death risk is <3%. The benefit from CEA in asymptomatic women is significantly less than in men. CEA should therefore be considered only in younger, fit women. The European Society for Vascular Surgery Eur J Vasc Endovasc Surg Apr;37(4 Suppl):1-19

32 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease: Recommendations for Selection of Patients for Carotid Revascularization Class I 3. Selection of asymptomatic patients for carotid revascularization should be guided by an assessment of comorbid conditions, life expectancy, and other individual factors and should include a thorough discussion of the risks and benefits of the procedure with an understanding of patient preferences. (Level of Evidence: C) Class IIa 1. It is reasonable to perform CEA in asymptomatic patients who have more than 70% stenosis of the internal carotid artery if the risk of perioperative stroke, MI, and death is low. (Level of Evidence: A)

33 Asymptomatic Carotid Stenosis: Recommendations 1. Patients with asymptomatic carotid stenosis should be prescribed daily aspirin and a statin. Patients should also be screened for other treatable risk factors for stroke, and appropriate medical therapies and lifestyle changes should be instituted (Class I; Level of Evidence C). 2. In patients who are to undergo CEA, aspirin is recommended perioperatively and postoperatively unless contraindicated (Class I; Level of Evidence C). 3. It is reasonable to consider performing CEA in asymptomatic patients who have >70% stenosis of the internal carotid artery if the risk of perioperative stroke, MI, and death is low (<3%). However, its effectiveness compared with contemporary best medical management alone is not well established (Class IIa; Level of Evidence A). Guidelines for the Primary Prevention of Stroke : A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke.2014; 45:

34 Asymptomatic Carotid Stenosis: Recommendations - continue 4. It is reasonable to repeat duplex ultrasonography annually by a qualified technologist in a certified laboratory to assess the progression or regression of disease and response to therapeutic interventions in patients with atherosclerotic stenosis >50% (Class IIa; Level of Evidence C). 5. Prophylactic CAS might be considered in highly selected patients with asymptomatic carotid stenosis (minimum, 60% by angiography, 70% by validated Doppler ultrasound), but its effectiveness compared with medical therapy alone in this situation is not well established (Class IIb; Level of Evidence B). 6. In asymptomatic patients at high risk of complications for carotid revascularization by either CEA or CAS, the effectiveness of revascularization versus medical therapy alone is not well established (Class IIb; Level of Evidence B). 7. Screening low-risk populations for asymptomatic carotid artery stenosis is not recommended (Class III; Level of Evidence C).

35 Algorithm for the management of extracranial carotid artery disease. The European Society of Cardiology Tendera M et al. Eur Heart J 2011;32:

36 7.1. Recommendations for Selection of Patients for Carotid Revascularization* Class I 1. Patients at average or low surgical risk who experience nondisabling ischemic stroke or transient cerebral ischemic symptoms, including hemispheric events or amaurosis fugax, within 6 months (symptomatic patients) should undergo CEA if the diameter of the lumen of the ipsilateral internal carotid artery is reduced more than 70% as documented by noninvasive imaging (Level of Evidence: A) or more than 50% as documented by catheter angiography (Level of Evidence: B) and the anticipated rate of perioperative stroke or mortality is less than 6%. 2. CAS is indicated as an alternative to CEA for symptomatic patients at average or low risk of complications associated with endovascular intervention when the diameter of the lumen of the internal carotid artery is reduced by more than 70% as documented by noninvasive imaging or more than 50% as documented by catheter angiography and the anticipated rate of periprocedural stroke or mortality is less than 6%. (Level of Evidence: B) ASA, AANN, AHA, etc guidelines

37 Class IIa 2. It is reasonable to choose CEA over CAS when revascularization is indicated in older patients, particularly when arterial pathoanatomy is unfavorable for endovascular intervention (Level of Evidence: B) 3. It is reasonable to choose CAS over CEA when revascularization is indicated in patients with neck anatomy unfavorable for arterial surgery. (Level of Evidence: B) 4. When revascularization is indicated for patients with TIA or stroke and there are no contraindications to early revascularization, intervention within 2 weeks of the index event is reasonable rather than delaying surgery. (Level of Evidence: B Class IIb 2. In symptomatic or asymptomatic patients at high risk of complications for carotid revascularization by either CEA or CAS because of comorbidities, the effectiveness of revascularization versus medical therapy alone is not well established. (Level of Evidence: B)

38 סיבות מקובלות לטיפול בצנתור הורית נגד לניתוח מיקום בלתי נגיש בצוואר הצרות חוזרת לאחר ניתוח CEA הצרות לאחר הקרנות לצוואר התוויה חדשה חולים צעירים (אך הגברת סיכון להצרות חוזרת)

39 Class IIb 2. In symptomatic or asymptomatic patients at high risk of complications for carotid revascularization by either CEA or CAS because of comorbidities, the effectiveness of revascularization versus medical therapy alone is not well established. (Level of Evidence: B)

40 Screening for Asymptomatic Carotid Artery Stenosis: U.S. Preventive Services Task Force Recommendation Statement. Ann. Intern. Med. Sep 2014: 356.

41 Risk factors associated with asymptomatic carotid stenosis Severity of the stenosis? no!? Stenosis progression -?? Age questionable for elderly patients (because they don t live long enough to show benefit!) Gender males, questionable for females Clinical circumstances -?? Patients characteristics -?? Plaque characteristics -!?

42 Relevant indicators (for higher risk) 1. Identification of a vulnerable plaque -New modalities under investigation include functional imaging of the plaque using positron emission tomography (PET) with CT, MRI, ultrasonic plaque texture analysis,16 contrast enhanced ultrasound (CEUS) techniques etc. -Analysis of plasma biomarkers 2. Measuring cerebrovascular reactivity (CVR) 3. Micro-embolic signals (MES) 4. Associated silent brain infarcts (SBI)

43 impaired CVR and stroke risk Meta-analysis of the Asymptomatic Carotid Emboli Study (ACES) data with previous studies, impaired CVR was associated with increased risk of: - ipsilateral stroke alone (OR, 6.14; 95% CI, ; P=0.02), - ipsilateral stroke or TIA (OR, 4.76; 95% CI, ; P=0.001), and - any stroke (OR, 4.66; 95% CI, ; P=0.003). King A et al, ACES Investigators: Stroke; 2011;42:1550-5

44 Micro-Embolic Signals (MES)

45 Prevalence of HITS in 70% and 70% asymptomatic stenosis. HITS, High intensity transient signals (= MES). Jayasooriya G et al. Review, J Vasc Surg 2011;54:227-36

46 Stroke risk in TCD emboli positive and negative subjects with asymptomatic carotid stenosis. Jayasooriya G et al. Review, J Vasc Surg 2011;54:227-36

47 Silent brain infarcts (SBI) SBI s are common in patients at increased risk of stroke The presence of silent infarcts more than doubles the risk of subsequent stroke and dementia. Similar adverse associations were found in patients with asymptomatic significant carotid stenosis. (SBI+) (SBI-)

48 LEUKO-ARAIOSIS (LA) Radiological Term of Greek Roots 1. LEUKO = White 2. ARAIOSIS = Rarefaction, of loose texture

49 אין אפשרות להציג תמונה זו כעת.

50 Freedom from Any Stroke by Degree of Leukoaraiosis 1.0 Proportion Event-Free Degree of Leukoaraiosis None Mild Moderate to Severe Study Time (Years)

51 Influence of Cerebral Infarcts & White Matter Lesions in Patients with Carotid Stenosis Both cerebral infarcts (silent, watershed internal borderzone or cortical) and WML (leukoaraiosis) are frequently found in patients with significant carotid stenosis. As these lesions are associated with a worse outcome especially in the perioperative period, they should be recognized and taken into account before deciding on any therapeutic approach (especially invasive interventions). Preventive measures and early recognition and treatment of carotid disease may, on the other hand, reduce this increased risk.