Stroke prevention a reality in this millennium

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  • Today, anti-platelets, lipid lowering agents and ACE inhibitors are being used for stroke prevention. Anti-platelets and lipid lowering certainly play an important role. Today, I will restrict my talk on ACE inhibitors in stroke prevention.
  • But why ACE inhibitors… ACE inhibitors, in addition to their blood pressure lowering effect also have some additional properties which could contribute to stroke prevention. Like…(please read the slide). What is the clinical evidence ?
  • PROGRESS sought to determine whether in patients with a history of stroke or TIA, treatment with perindopril + indapamide reduced the risk of recurrent stroke and major vascular events. This study was initiated by WHO-ISH and patients were recruited from 10 countries across the world.
  • To be selected patients had to have evidence of a stroke or TIA after 2 weeks but within 5 years of the acute event. Thus, all patients had a history of stroke. Additionally, the patients had to have no definite indication (such as heart failure) or contraindication (such as previous intolerance) to an ACE inhibitor. Patients selected were…
  • … hypertension under treatment (excluding ACE inhibitor), normotensive patients or those with other disease such as diabetes were also included in the study. PROGRESS therefore studied a broad range of associated disease that may occur with a history of stroke, as would be seen in daily practice. Importantly patients were treated with perindopril/control over and above other antihypertensive treatment.
  • As was expected, because of the randomisation, both groups were balanced at baseline. About 50% had hypertension and received antihypertensive therapy, which means that no patient was left without antihypertensives if required. What was the effect of treatment on total stroke, the primary outcome?
  • The effects of treatment started to appear within one year, and progressively fewer strokes occurred in the treatment group compared to placebo. Overall, after about 4 years the stroke risk reduction in the active group was 28% with a confidence interval of 17-38%. The results on stroke subtypes were similar.
  • The results on fatal/disabling stroke were significantly higher at 33% risk reduction and this was also manifested for non-fatal stroke by a risk reduction of 24%.
  • Treatment with perindopril + indapamide reduced ischaemic stroke risk by one quarter, and haemorrhage stroke risk by one half.
  • Risk reduction in stroke was seen in normotensive as well as in hypertensives.
  • Total withdrawal rate was nearly the same with treatment as with placebo. Of the major causes of withdrawal, cough was just 2% and hypotension which is a major concern in post stroke treatment was infrequent. Thus perindopril based treatment is acceptable for the long-term prevention of secondary stroke. … was the treatment easy to comply with ? Like the EUROPA trial the treatment acceptability is good even in the PROGRESS trial.
  • Please read the slide.
  • Please read the slide.
  • If we take into consideration the recent review published in the journal Stroke, the NNT with perindopril is only 23 vs. 67 with ramipril. Thus perindopril appears to be a more powerful treatment in secondary stroke prevention. Even the latest JNC-7 refers only to the PROGRESS trial with perindopril for stroke prevention. Given the significant public health impact of stroke, it is certainly advisable to consider these preventive measures for all patients.
  • high-sensitivity C-reactive protein, an inflammatory biomarker, independently predicts future vascular events. JUPITER trial was done in subjects with no prior cardiovascular disease or diabetes, LDL <130 mg/dL, and hsCRP level of 2 more than 2 mg/dL. Subjects were randomized to rosuvastatin 20mg daily or matching placebo. Follow up was done up to 60 months after randomization. The primary outcome was the occurrence of a first major cardiovascular event, defined as nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, an arterial revascularization procedure, or confirmed death from cardiovascular causes. Secondary end points included the components of the primary end point considered individually — arterial revascularization or hospitalization for unstable angina, myocardial infarction, stroke, or death from cardiovascular causes — and death from any cause.
  • All of these guidelines must be taken in context of the surgeon performing the procedure. The benefits seen with symptomatic carotid endarterectomies only outweigh the risks involved when the surgeon performing the procedure has a 6% or less morbidity/mortality rate. This low complication rate has been proven to be associated with surgeons in high-volume centers. 1, 2 Age >75 should not be an exclusion for endarterectomy. In fact, some studies suggest they may benefit more than younger patients. 3 1 North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET). Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991; 325:445-53. 2 Cina, et al. Cochrane Database Review, 2000 3 Alamowitch, et al. Lancet, 2001
  • Data from Rothwell, et al, found that the highest risk period after stroke is within the first 2 weeks, and that the event rate declined over time. The figure above demonstrates the absolute risk reduction with surgery, and the different color bars represent critical and high-grade stenoses. The confidence intervals begin to cross 0 at 2-4 weeks for high-grade, and >12 weeks for critical carotid stenoses. This has led to the recommendation that symptomatic, ipsilateral carotid endarterectomy be performed within 2 weeks of the initial event, instead of the previous tendency for a “cooling off” period. Rothwell, et al, Lancet 2004
  • The direct comparison between carotid endarterectomy and carotid stenting is being studied in the ongoing CREST trial, funded by the NIH. Previous studies have had smaller numbers, included inexperienced operators, or did not include distal protection which is usually considered standard practice currently. The SAPPHIRE trial randomized 334 patients to endarterectomy or stenting (with distal protection), and found that stenting was not inferior to endarterectomy, and in fact had lower event rates in the stenting arm. Most of this suggestion of benefit was a lower risk of myocardial infarction in high-risk patients. More definitive data is needed before recommendation of widespread stenting of extracranial carotid disease. Yadav, et al, NEJM 2004.
  • Atrial fibrillation (whether persistent or paroxysmal) is recognized as a potent risk factor for recurrent stroke and the data is strong that supports the use of warfarin to reduce this risk. Multiple clinical trials 1,2,3 , including the European Atrial Fibrillation trial 2 , support this recommendation. Only patients unable to tolerate oral anticoagulants should be administered aspirin for prevention, due to the clear superiority of warfarin in these patients. 2,3 1 Hylek EM et al. N Engl J Med 1996;335:540-546 2 EAFT Study Group. Lancet 1993;342:1255-1262 3 SPAF III investigators. Lancet 1996;348:633-638
  • Since the 1999 guidelines, there has been increasing evidence to support the fact that NONCARDIOEMBOLIC ischemic strokes should receive antiplatelet agents, not oral anticoagulants, for secondary stroke prevention. This recommendation is supported by the WARSS 1 and WASID 2 studies, in which aspirin was compared to warfarin and aspirin was safer with equal risk reduction. 1 Mohr JP et al. N Engl J Med 2001;245:1444-1451 2 Chimowitz MLM et al. Stroke 2004;35:235
  • Although stroke experts may disagree on which specific antiplatelet agent to use in a given patient, all agree on the importance of antiplatelet therapy in patients with noncardioembolic ischemic stroke. Based on the results of multiple clinical trials, all of the agents listed above are considered acceptable first line options. Since direct head-to-head comparisons demonstrating equivalence DO NOT exist, this is a Class IIa recommendation.
  • Statements regarding the choice between antiplatelet agents is more controversial. Although all can agree on the safety of the three agents, the combination of aspirin and extended-release dipyridamole is suggested over aspirin alone, based primarily on the results of ESPS2 1 . It is a Class IIa recommendation because other trials of dipyridamole alone were negative. It is considered Level A because of other positive trials of the combination. 2 The suggestion to use clopidogrel over aspirin is based on the CAPRIE study. 3 It is considered Class IIb because the effect was NOT significant in the patients included because of prior stroke. It is Level B because it is based on a single trial. The use of ticlopidine is no longer recommended due to its side effect profile (excessive diarrhea and blood dyscrasias) and failure to provide significant benefit. In addition, a recent study in African Americans, showed no benefit over aspirin alone (AAAPS)4. 1 Diener HC et al. J Neurosci 1996;143:1-13 2 ESPS. Lancet 1987;2:1351-1354 3 CAPRIE Steering Committee. Lancet 1996;384:1329-1339 4 Gorelick PB et al. JAMA 2003; 289:2947-2957
  • Additional recommendations regarding antiplatelet recommendations include a strong recommendation against the use of the combination of clopidogrel and aspirin in patients with stroke or TIA, based on the lack of additional benefit over clopidogrel alone but an excess bleeding risk. This is based on the results of the MATCH trial. 1 The only time these agents should be used together in stroke patients is when the patient has had a myocardial event within the past 9-12 months, based on the CURE study. 2 For patients allergic to aspirin, clopidogrel is recommended based on the CAPRIE study. 3 1 Diener HC et al. Lancet 2004;364:331-337 2 Yusuf S et al. N Engl J Med 2001;345:494-502 3 CAPRIE Steering Committee. Lancet 1996;348:1329-1339
  • Bleeding events were significantly increased in patients receiving aspirin / clopidogrel combination therapy.
  • Examples of high-risk conditions include known coagulopathies or prosthetic heart valves.
  • Rossouw, et al, JAMA 2002
  • All of the strongest recommendations are listed above, both Class I and Class III, with level A evidence (multiple clinical trials).
  • The direct comparison between carotid endarterectomy and carotid stenting is being studied in the ongoing CREST trial, funded by the NIH. Previous studies have had smaller numbers, included inexperienced operators, or did not include distal protection which is usually considered standard practice currently. The SAPPHIRE trial randomized 334 patients to endarterectomy or stenting (with distal protection), and found that stenting was not inferior to endarterectomy, and in fact had lower event rates in the stenting arm. Most of this suggestion of benefit was a lower risk of myocardial infarction in high-risk patients. More definitive data is needed before recommendation of widespread stenting of extracranial carotid disease. Yadav, et al, NEJM 2004.
  • All of the strongest recommendations are listed above, both Class I and Class III, with level A evidence (multiple clinical trials).
  • Stroke prevention a reality in this millennium

    1. 1. STROKE PREVENTION- A REALITY IN THIS MILLENNIUM Prof. A.V. SRINIVASAN, MD, DM, Ph.D, F.A.A.N, F.I.A.N. Emeritus Professor The Tamilnadu Dr. M.G.R. Medical University Former Head Institute of Neurology, Madras Medical College 21-08-10
    2. 2. Cerebrovascular Prevention Is survival a mere stroke of Luck?“My Opinions are founded on knowledge but modified by experience”
    3. 3. INTRODUCTION Perceptual Sense(Observation) Word Sense (Recording) Common Sense (Thinking)  Will lead you to get - Clinical Sense “ He who cannot forgive others destroys the bridge over which he himself must pass” - Annoy
    4. 4. Cerebrovascular disease – Mind boggling facts World wide incidence: 2/1000 population/annum 1 Incidence in people aged 45 – 84 years: about 4/1000 1 Incidence in India: was 36/100,000 for the year 1998-1999 3 in a study in Calcutta Incidence of mortality due to stroke (India: WHO study): 73/100,000 per year2CVD is the most disabling of all neurologic diseases.50% of survivors have a residual neurologic deficit. Greater than 25% require chronic care. 1.A practical approach to management of stroke patients; 1996; 360-384 2. Epidemology of cerebrovascular disorders in India; 1999; 4-19 3. Neuroepidemiology 2001;20:201-207 If you think you can or you can’t You are always right
    5. 5. Annual risk CVD, MI, vascular death following TIA, minor CVD• CVD 6.7 %• MI 2.5 %• Death 7.2 %• CVD, MI, Vascular death 8.6 %• CVD, MI, Death 10.3 % Experience can be defined as yesterday’s answer to today’s problems
    6. 6. Common Stroke Mimics Hypoglycemia Post ictal state Drug overdose Concussion with neck injury Migrainous accompaniment Encephalopathies with focal signs Hyponatremia Subdural hematoma, Empyema Focal Encephalitis: Herpes Being ignorant is not so much a shame as being unwilling to learn
    7. 7. Drugs used for stroke prevention… ACE inhibitors Lipid lowering agent Anti-platelets
    8. 8. Prevention ofCerebrovascular Events with Perindopril: New Evidence
    9. 9. Why ACE inhibitors in stroke prevention ? Blood pressure lowering effect Prevention of endothelial dysfunction Prevention of progression of atherosclerosis Favourable alteration of the fibrinolytic balance Prevention of cardiac remodelling Clinical evidence…
    10. 10. Objective of PROGRESSWhether in patients with… Stroke OR TIA Perindopril + Indapamide Risk of stroke & vascular events WHO – ISH initiated the studyPROGRESS collaborative group. Lancet 2001;358:1033-41.
    11. 11. Patient selection criteria Evidence of Stroke / TIA > 2 weeks and < 5 years of event …but without a definite indication / contraindication to treatment with an ACE inhibitorPROGRESS collaborative group. Lancet 2001;358:1033-41.
    12. 12. Patient selection criteria Young Diabetic Non-diabetic IncludedHypertensive Normotensive OldPROGRESS collaborative group. Lancet 2001;358:1033-41.
    13. 13. Baseline characteristics Characteristic Perindopril + indapamide Placebo N = 3051 N = 3054 Mean age (yrs) 64 64 Females (%) 30 30 Stroke history  Ischaemic stroke (%) 71 71  Haemorrhagic stroke (%) 11 11  TIA (%) 22 22  Duration since event (months) 8 8 Diabetes (%) 13 12 CAD (%) 16 16 Mean BP (mmHg) 147/86 147/86 Hypertension (%) 48 48 Antihypertensive therapy (%) 50 51PROGRESS collaborative group. Lancet 2001;358:1033-41.
    14. 14. Total stroke 28% 28% Placebo group risk risk reduction Risk reduction (%) reduction 38% Active group 0 1 2 3 4 YearsPROGRESS collaborative group. Lancet 2001;358:1033-41.
    15. 15. Stroke subtype (1) Fatal / Non fatal / disabling stroke disabling stroke 24 33 Risk reduction (%)PROGRESS collaborative group. Lancet 2001;358:1033-41.
    16. 16. Stroke subtype (2) Ischaemic Haemorrhagic stroke stroke 24 50 Risk reduction (%)PROGRESS collaborative group. Lancet 2001;358:1033-41.
    17. 17. Hypertensives / normotensives Stroke Hypertensives Normotensives 27 32 Risk reduction (%)PROGRESS collaborative group. Lancet 2001;358:1033-41.
    18. 18. Treatment acceptability Active group Causes of withdrawal (%) Placebo 23 21 8 8 2 2 0.9 0.4 All causes Voluntary Cough HypotensionPROGRESS collaborative group. Lancet 2001;358:1033-41.
    19. 19. PROGRESS results showed… Perindopril+ indapamide substantially reduced risk of secondary stroke and other vascular events Irrespective of  Age  Blood pressure level  Other diseases  Background medication PROGRESS collaborative group. Lancet 2001;358:1033-41.
    20. 20. Summarise… ACE inhibitors are beneficial in the prevention of stroke All stroke patients, hypertensive as well as normotensives should receive an ACE inhibitor All CAD patients, diabetic patients, who are at-risk of developing stroke should receive an ACE inhibitor Which ACE inhibitor ?
    21. 21. Which ACE inhibitor ? Treatment Number-needed-to-treat Perindopril- 23 to prevent based therapy 1 stroke in 5 years Ramipril-based 67 to prevent therapy 1 stroke in 5 years JNC – 7 reference only to perindoprilStroke 2002;33:862-875. JNC-7, JAMA May 2003 – Vol.289; No.19: 2560-2571.
    22. 22. Statins: Stroke Prevention andSurvival Benefits
    23. 23. Primary Prevention of Ischemic Stroke A Guideline From the American Heart Association/American Stroke Association Stroke Council It is recommended that patients with known CAD and high-risk hypertensive patients even with normal LDL cholesterol levels be treated with lifestyle measures and a statin (Class I, Level of Evidence A). Stroke 2006;37;1583-1633
    24. 24. JUPITER & STROKE JUPITER is the first large-scale, prospective study to examine the role of statin therapy in individuals with low to normal LDL-C levels, but with increased cardiovascular risk identified by elevated CRP Nearly half of all cardiovascular events occur in patients who are apparently healthy and who have low or normal levels of LDL-C hsCRP predicts cardiovascular disease independent of LDL-C levels
    25. 25. JUPITER JUPITERTrial Design Multi-National Randomized Double Blind Placebo Controlled Trial of Rosuvastatin in the Prevention of Cardiovascular Events Among Individuals With Low LDL and Elevated hsCRP Rosuvastatin 20 mg (N=8901)No Prior CVD or DM Men >50, Women >60 LDL <130 mg/dL 4-week Placebo (N=8901) hsCRP >2 mg/L run-in Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Costa Rica, Denmark, El Salvador, Estonia, Germany, Israel, Mexico, Netherlands, Norway, Panama, Poland, Romania, Russia, South Africa, Switzerland, United Kingdom, Uruguay, United States, Venezuela Ridker et al, Circulation 2003;108:2292-2297.
    26. 26. JUPITER: Results No. of patients with any stroke 70 64 60 48% 50 Reduction 40 33 * 30 20 10 0 Rosuvastatin Placebo n=8901 n=8901 Circulation 2010;121:143-150* p< 0.002 vs. placebo
    27. 27. JUPITER: Results No. of patients with non-fatal stroke 60 58 50 48% 40 Reduction 30 * 30 20 10 0 Rosuvastatin Placebo n=8901 n=8901 Circulation 2010;121:143-150* p< 0.003 vs. placebo
    28. 28. JUPITER: Results No. of patients with fatal stroke 6 6 50% 5 Reduction 4 3 3 2 1 0 Rosuvastatin Placebo n=8901 n=8901Circulation 2010;121:143-150
    29. 29. JUPITER: Results No. of patients with ischemic stroke 50 47 45 51% 48% 40 35 Reduction 30 * 23 25 20 15 10 5 0 Rosuvastatin Placebo n=8901 n=8901 Circulation 2010;121:143-150* p< 0.004 vs. placebo
    30. 30. Primary Prevention of Stroke:What do the previousstatins trials suggest?
    31. 31. WOSCOPS STUDY: Statin: Pravastatin 40 mg AFCAPS/TexCAPS STUDY: n=6595 Statin: Lovastatin 10-40 mg Results: Stroke 11% n=6605 Results: Stroke 18%MEGA STUDY: JUPITER STUDY:Statin: Pravastatin 10-20 mg Statin: Rosuvastatin 20 mgn=7730 n=17802Results: Stroke 17% Results: Stroke 48% Circulation 2010;121:143-150
    32. 32. A meta-analysis of WOSCOPS+AFCAPS/TexCAPS+MEGA •Stroke reduction by 14% (statistically non- significant)A meta-analysis of these 3 trials along with JUPITER •Stroke reduction by 25% (statistically significant)Analysis of JUPITER only:Stroke reduction by 48% (statistically non-significant)
    33. 33. Summary Stroke is one of the leading cause of death worldwide. Guidelines recommends the use of statins for primary as well as secondary prevention of stroke. JUPITER trial has established that rosuvastatin is the most effective statin in preventing stroke in high risk population.
    34. 34. Symptomatic Carotid Endarterectomy ASA 2006 Secondary Stroke Recs• Ipsilateral severe (70% to 99%) carotid stenosis,CEA is recommended (Class I, Evidence A).• Ipsilateral moderate (50% to 69%) carotid stenosis,CEA is recommended depending on age, gender,comorbidities, and the severity of symptoms (Class I,Evidence A).• Stenosis <50%, there is no indication for CEA (ClassIII, Evidence A).
    35. 35. Urgent EndarterectomySurgery within 2 weeks is suggested rather than delaying surgery(Class IIa, Evidence B).Rothwell PM. Lancet 2004;363(9413):915-24
    36. 36. Carotid Angioplasty and Stenting ASA 2006 Secondary Stroke Recs• CAS may be considered (Class IIb, Evidence B). - Stenosis (>70%) difficult to access surgically - Medical conditions that greatly increase the risk for surgery, or - When other circumstances exist such asradiation-induced stenosis or restenosis afterCEA.• CAS is reasonable when performed by operators with morbidity and mortality rates of 4% to 6% (Class IIa, Evidence B).
    37. 37. Atrial Fibrillation ASA 2006 Recommendations• For patients with ischemic stroke or TIA withpersistent or paroxysmal (intermittent) AF,anticoagulation with adjusted-dose warfarin (target INR2.5, range 2.0 to 3.0) is recommended (Class I,Evidence A).• For patients unable to take oral anticoagulants,aspirin 325 mg per day is recommended (Class I,Evidence A).
    38. 38. Stroke Prevention: Non-cardioembolic ASA 2006 RecommendationsFor patients with noncardioembolic ischemicstroke or TIA, antiplatelet agents arerecommended rather than oral anticoagulation toreduce the risk of recurrent stroke and othercardiovascular events (Class I, Evidence A).
    39. 39. Stroke Prevention: Non- cardioembolic ASA 2006 Recommendations• Acceptable options for initial therapy (Class IIa, Evidence A). - aspirin (50-325 mg qd) - the combination of aspirin and extended-release dipyridamole (25/200 mg bid) - clopidogrel (75 mg qd)
    40. 40. Antiplatelet Therapy ASA 2006 Recommendations• Compared to aspirin alone, both the combination ofaspirin and extended-release dipyridamole andclopidogrel are safe.• The combination of aspirin and extended-releasedipyridamole is suggested instead of aspirin alone(Class IIa, Level A).• Clopidogrel is suggested instead of aspirin alonebased on direct comparison trials(Class IIb, Level B).
    41. 41. Secondary Stroke Prevention ASA 2006 Recommendations• Insufficient data are available to make evidence-based recommendations regarding choices betweenantiplatelet options other than aspirin. Selection of anantiplatelet agent should be individualized based onpatient risk factor profiles, tolerance, and other clinicalcharacteristics.
    42. 42. Secondary Stroke Prevention ASA 2006 Recommendations• The addition of aspirin to clopidogrel increasesthe risk of hemorrhage and is not routinelyrecommended for stroke or TIA patients (ClassIII, Evidence A).• For patients allergic to aspirin, clopidogrel isrecommended (Class IIa, Evidence B).
    43. 43. MATCH: Safety Outcomes • Excess life-threatening bleeding events with combination versus clopidogrel monotherapy: 96 (2.6%) vs. 49 (1.3%); p<0.0001 • Excess minor bleeds with combination therapy versus clopidogrel alone: 120 (3.2%) vs. 39 (1.0%); p<0.0001Diener H-C et al. Lancet 2004;364:331-7
    44. 44. Secondary Stroke Prevention ASA 2006 Recommendations• For patients who have an ischemiccerebrovascular event while taking aspirin,there is no reliable evidence that increasing thedose of aspirin provides additional benefit.Although alternative antiplatelet agents areoften considered for these patients, no singleagent or combination has been specificallyevaluated in patients who have had an eventwhile receiving aspirin.
    45. 45. Stroke and PregnancyASA 2006 Secondary Stroke Recs• High-risk thromboembolic conditions consider: - adjusted-dose UFH throughout pregnancy, - adjusted-dose LMWH with Factor Xa monitoring - UFH or LMWH until week 13, followed bywarfarin until mid-3rd trimester, then UFH orLMWH in last trimester (Class IIb, EvidenceC).• Lower risk conditions - UFH or LMWH in the first trimester followed by - low-dose aspirin for the remainder of the pregnancy (Class IIb, Evidence C).
    46. 46. Postmenopausal HormonesASA 2006 Secondary Stroke RecsFor women with ischemic stroke or TIA,postmenopausal hormone therapy (with estrogenwith or without a progestin) is not recommended(Class III, Evidence A).
    47. 47. Women’s Health Initiative • 16,608 postmenopausal women, 50-79 years, with an intact uterus at baseline were recruited by 40 U.S. clinical centers for the period 1993- 1998. • Received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). • After a mean of 5.2 years of follow-up, the trial was stopped because of high rates of invasive breast cancer and the global index statistic supported risks exceeding benefits.Rossouw et al. JAMA 2002;288(3):321-33
    48. 48. Other CircumstancesASA 2006 Secondary Stroke Recs• Dissections• PFO and hyperhomocysteinemia• Hypercoagulable states• Sickle cell disease• Cerebral venous thrombosis• Anticoagulation after cerebral hemorrhage
    49. 49. Level A Recommendations• Antihypertensive treatment• Glucose control to reduce microvascularcomplications of diabetes• Statins to reduce LDL to <100 or <70 for high-risk patients (sympt CHD or athero)• CEA for sympt 50-99%• NO CEA for <50% sympt stenosis• Warfarin at INR 2.5 for Afib. (ASA if unable)• Antiplatelet for noncardioembolic• NO combination clopidogrel and ASA
    50. 50. Carotid Angioplasty and Stenting ASA 2006 Secondary Stroke Recs• CAS may be considered (Class IIb, Evidence B). - Stenosis (>70%) difficult to access surgically - Medical conditions that greatly increase the risk for surgery, or - When other circumstances exist such asradiation-induced stenosis or restenosis afterCEA.• CAS is reasonable when performed by operators with morbidity and mortality rates of 4% to 6% (Class IIa, Evidence B).
    51. 51. Other CircumstancesASA 2006 Secondary Stroke Recs• Dissections• PFO and hyperhomocysteinemia• Hypercoagulable states• Sickle cell disease• Cerebral venous thrombosis• Anticoagulation after cerebral hemorrhage
    52. 52. Level A Recommendations• Antihypertensive treatment• Glucose control to reduce microvascularcomplications of diabetes• Statins to reduce LDL to <100 or <70 for high-risk patients (sympt CHD or athero)• CEA for sympt 50-99%• NO CEA for <50% sympt stenosis• Warfarin at INR 2.5 for Afib. (ASA if unable)• Antiplatelet for noncardioembolic• NO combination clopidogrel and ASA
    53. 53. PROGNOSTIC PEARLS Flaccid Paralysis for more than 96 hrs When tendon reflexes recover without return of voluntary movement – prognosis poor Recovery of sensory less in usual to a degree. Postion sense recovers but not pain and temperature Recovery from Dysphasia is never complete Dysarthria usual improves and Dysphagia never improves Diplopia due to brain stem is usually permanent Conjugate gaze – recovers Vertigo improves but hearing loss is permanent Pseudobulbar palsy permanent “ByNature All Men/W en are alike but om byEducation widelydifferent”
    54. 54. CVD – Prevention or Cure?While number of curative methods are available, preventive therapy is undoubtedly the main strategy in the management of CVD Lijec Vjesn. 2003 Nov-Dec;125(11-12):322-8 The sign wasn’t placed there By the Big Printer in the sky
    55. 55. Dedicated to my family formaking everything worthwhile
    56. 56. READ not to contradict or confuteNor to Believe and Take for Grantedbut TO WEIGH AND CONSIDERTHANK YOUMy sincere thanks to Serdia pharmaceuticals

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