Prevention of Ischemic Stroke

Aka: Prevention of Ischemic Stroke, Cerebrovascular Risk Factor Modification, Risk Factor Modification Following Transient Ischemic Attack, Anticoagulation in Ischemic Stroke, Cerebrovascular Accident Prevention, Carotid Stenosis Medical Management, CVA Prevention, Prevention of Recurrent Cerebrovascular Accident, Antiplatelet Therapy in CVA and TIA

advertisement

II. Indications

  1. Post-stroke antithrombotic therapy
  2. Atrial Fibrillation
    1. See Atrial Fibrillation Anticoagulation

III. Management: Short term prevention after Ischemic Stroke and Transient Ischemic Attack

  1. Aspirin monotherapy (first choice, unless dual therapy initially indicated as below)
    1. Dose 81 to 325 mg orally daily indefinately
    2. CVA reduction of 1% with Aspirin by IST trial
    3. Effective in acute CVA therapy as well as prevention
    4. If recurrent stroke on Aspirin
      1. Consider initial combined Clopidogrel and Aspirin for 3 weeks, then Clopidogrel (see below)
      2. No evidence that raising Aspirin dose (e.g. 325 mg) decreases recurrent CVA risk over 81 mg
  2. Clopidogrel monotherapy
    1. Dose 75 mg orally daily
    2. Consider in patients with allergy to Aspirin
    3. In prevention of recurrent CVA or TIA, similar efficacy to Aspirin monotherapy and Aggrenox
  3. Aspirin and Clopidogrel (first 3 weeks after minor CVA, high risk TIA)
    1. Indications
      1. Immediately following mild ischemic Cerebrovascular Accident (CVA) with NIH Stroke Scale <=3
      2. Immediately after high risk Transient Ischemic Attack (TIA) with ABCD2 Score >=4
    2. Not recommended for longterm use
    3. Protocol
      1. Combination protocol for 10-21 days (typically 21 days)
        1. Aspirin 81 mg daily and
        2. Clopidogrel 75 mg daily (after initial single loading dose of 300 mg)
      2. After 3 weeks
        1. Discontinue one of the antiplatelet agents (typically stopping Clopidogrel)
        2. Continue Aspirin indefinately as above
    4. Efficacy
      1. Decreases risk of recurrent TIA or CVA in short term (NNT 29 compared with Aspirin alone)
      2. Not effective long-term (and should not be used for this due to increased bleeding risk) - see below
    5. Adverse effects
      1. Major bleeding occurs in 1 in 200 patients (but does not increase Intracranial Bleeding risk)
    6. References
      1. Prasad (2018) BMJ 363:k5130 +PMID:30563885 [PubMed]
      2. Wang (2015) Circulation 132(1): 40-6 [PubMed]
      3. Wang (2013) N Engl J Med 369(1):11-9 [PubMed]
  4. Aspirin and Dipyridamole (Aggrenox)
    1. Similar efficacy to Aspirin monotherapy, but less well tolerated
  5. Low dose non-bolus Heparin (use is variable)
    1. Efficacy
      1. No evidence of benefit in CVA evolution
      2. Less Hemorrhage than ASA by IST trial
      3. CVA reduction 1-2%
      4. Not indicated in most cases (risk without benefit)
        1. Stead (2004) Ann Emerg Med 44:540-2 [PubMed]
    2. Dosing: Goal is PTT approximately twice normal
      1. Dose: 12 u/kg/h (NO bolus, by actual weight)
    3. Indications
      1. Cardioembolic CVA
      2. Aortic arch atheroma
    4. Contraindications
      1. CT Head shows bleeding
      2. Endocarditis on native valve thromboembolic CVA
  6. Antihypertensives
    1. See below regarding precautions (do not lower BP on first day) and management strategies
    2. See CVA Blood Pressure Control for acute control
    3. Longterm Blood Pressure goal (after acute CVA stabilization): <130/80 mmHg
    4. ACE Inhibitor with a Diuretic (e.g. Lisinopril/hctz)
      1. Start immediately after hyperacute period
      2. Significantly reduces recurrent CVA risk
        1. (2001) Lancet 358:1033-41 [PubMed]
  7. Avoid potentially harmful interventions
    1. Heparin drip (Regular dose): Do Not Use
      1. No significant benefit by IST trial
      2. Risk of Hemorrhage (especially with bolus)
    2. Low Molecular Weight Heparin
      1. Dose dependent CVA reduction by Hong Kong Study
      2. No benefit and high Hemorrhage risk by TOAST study
    3. Warfarin (Coumadin)
      1. Not recommended in the prevention of Ischemic CVA
      2. Increased bleeding risk, and not more effective than Antiplatelet Therapy
      3. Halkes (2007) Lancet Neurol 6(2): 115-24 [PubMed]
    4. Emergent Anticoagulation not indicated
      1. Recurrent stroke in first 14 days is only 0.06%
      2. Can start in first 48 hours after CVA
      3. Bolus therapy is not indicated
    5. Do not lower Blood Pressure aggressively on first day
      1. See CVA Blood Pressure Control
    6. Ibuprofen
      1. Inactivates Aspirin positive effect
      2. Unclear if other NSAIDs also reduce Aspirin benefit

IV. Management: Long term prevention (Primary and Secondary Prevention)

  1. Evaluate for reversible and modifiable disease
    1. See Transient Ischemic Attack
    2. Carotid Endarterectomy
      1. See Carotid Stenosis for indications
      2. Typically carotid endarterectomy is recommended for Carotid Stenosis >70%
      3. Indications depend on patient perioperative risk, comorbidity, age and symptoms
    3. Evaluate for Arrhythmia (e.g. Atrial Fibrillation)
    4. Specific Conditions related to stroke requiring Anticoagulation, Antiplatelet Therapy or correction
      1. Antiphospholipid Antibody Syndrome
        1. Warfarin (INR 2 to 3) if syndrome is confirmed
        2. Antiplatelet Therapy if Antibody positive only
      2. Cardiomyopathy
        1. Warfarin (INR 2 to 3) for 3 months after Ischemic Stroke
      3. Carotid Artery Dissection or Vertebral Artery Dissection
        1. Anticoagulation for 3 months following stroke, then Antiplatelet Therapy
      4. Fibromuscular Dysplasia
        1. Urgent risk reduction (see below)
        2. Antiplatelet Therapy if dissection
      5. Temporal Arteritis (Giant Cell Arteritis)
        1. See Temporal Arteritis
        2. High dose Corticosteroids
      6. Hypercoagulable State
        1. Antiplatelet Therapy
      7. Left Ventricular Thrombus
        1. Myocardial Infarction complication
        2. Warfarin (INR 2 to 3) for 3 months after Ischemic Stroke
      8. Sickle Cell Disease
        1. Blood Transfusion to reduce Hemoglobin S to less than 30% of total Hemoglobin
    5. Surgery Indications following Cerebrovascular Accident
      1. See Carotid Endarterectomy as above
      2. Cardiac Tumor
      3. Infective Endocarditis
      4. Moyamoya Disease (Occlusive disease of Circle of Willis)
  2. Antiplatelet agents after CVA or TIA
    1. See Anticoagulation in Atrial Fibrillation
    2. First-Line options
      1. Background: Agent comparison
        1. Aspirin alone offers 18-22% Relative Risk Reduction of subsequent stroke or TIA
        2. Aggrenox or Plavix each offer a 37% Relative Risk Reduction of subsequent stroke or TIA
      2. Aspirin 81 to 325 mg daily
        1. Use concurrently with PPI if history of GI Bleeding on Aspirin
      3. Clopidogrel (Plavix) 75 mg daily
        1. Indicated if Aspirin intolerant or high risk
        2. Equivalent to Aggrenox in cerebrovascular event risk reduction
        3. Slightly lower risk of GI Bleeding than with Aggrenox
      4. Aspirin 50 mg with Dipyridamole 400 mg (Aggrenox)
        1. Consider over Aspirin in highest risk patients (TIA or CVA on Aspirin)
        2. Better efficacy over Aspirin alone (and similar to reduction with Plavix)
        3. Minimal increased risk of bleeding
        4. Poorly tolerated (stopped due to Headache in 25%) and twice daily
        5. Expensive! ($320 versus Aspirin $1 or Clopidogrel $10 per month)
        6. References
          1. Diener (1996) J Neurol Sci 143:1-13 [PubMed]
          2. Halkes (2006) Lancet 367:1665-73 [PubMed]
    3. Avoid Warfarin (Coumadin) after nonembolic stroke
      1. No advantage over Aspirin to prevent recurrent CVA
      2. Warfarin is indicated in thromboembolic stroke
      3. Mohr (2001) N Engl J Med 345:1444-51 [PubMed]
    4. Avoid combination of Aspirin and Clopidogrel longterm (aside from 3 week acute course)
      1. Bleeding risk outweighed small vascular benefit
        1. Diener (2004) Lancet 364:331-7 [PubMed]
      2. However consider for first 3 weeks following mild CVA or TIA
        1. See above (under short-term)
  3. Other measures
    1. Treat Coronary Artery Disease
    2. Optimize Diabetes Mellitus control
      1. Screen for Diabetes Mellitus (Fasting Glucose, Hemoglobin A1C, OGTT) in undiagnosed patients
      2. Maintain Blood Pressure <130/80 (most important)
      3. Maintain Fasting Glucose <126 mg/dl (Hemoglobin A1C <7%)
      4. Weight loss
    3. Manage Major Depression (up to 20% of patients after stroke)
      1. Screen for and treat comorbid Major Depression
      2. Reduces mortality after Ischemic Stroke
      3. Consider Selective Serotonin Reuptake Inhibitor
      4. Jorge (2003) Am J Psychiatry 160:1823-9 [PubMed]
    4. Tobacco Cessation
      1. Tobacco Cessation is the single most effective measure in CVA Prevention
      2. Risk of CVA is 50% higher in smokers
      3. Shinton (1999) BMJ 298:789-94 [PubMed]
    5. Control Hyperlipidemia
      1. Goal LDL Cholesterol <70-100 mg/dl
        1. LDL Cholesterol <70 mg/dl compared with 95 mg/dl decreases risk of CV event in 3.5 years (NNT 42)
          1. Amarenco (2019) N Engl J Med 382:9-19 [PubMed]
      2. High Intensity Statin Drugs are preferred
        1. Atorvastatin (Lipitor) 40 mg
        2. Rosuvastatin (Crestor) 20 mg
    6. Control Hypertension to Blood Pressure target (after initial 24 hours)
      1. Target Blood Pressure <140/90 mmHg (<130/80 for Lacunar Infarct, Diabetes Mellitus, CKD)
      2. Systolic Blood Pressure as a predictor of subsequent stroke (hazard ratios)
        1. Maximum systolic Blood Pressure: Hazard Ratio 15
        2. High variability in systolic Blood Pressure: Hazard Ratio 6
        3. Rothwell (2010) Lancet 375(9718): 895-905 [PubMed]
      3. Interventions
        1. See DASH Diet
        2. Hydrochlorothiazide (first line)
        3. ACE Inhibitors (in combination with Diuretic)
        4. Calcium Channel Blockers may lower Blood Pressure lability
    7. Alcohol only in moderation
      1. Alcohol in moderation (1-2 drinks per day in men) may reduce the risk of recurrent CVA
      2. Heavy Alcohol use (>2 drinks per day in men) increases the risk of recurrent CVA
        1. Mostofsky (2010) Stroke 41(9): 1845-9 [PubMed]
    8. Drug Abuse Cessation
      1. Cocaine and Methamphetamine increase risk of cardiovascular events
      2. Intravenous drug use increases risk of Infective Endocarditis
    9. Maintain regular Exercise >30 minutes, >3 days/week (120 to 150 min/week)
      1. High intensity Exercise is associated with a 64% CVA Relative Risk Reduction
      2. Lee (2003) Stroke 34(10): 2475-81 [PubMed]
    10. Fish intake (1-4 servings per month)
      1. Lowered Ischemic Stroke risk by 40%
      2. He (2002) JAMA 288:3130-6 [PubMed]
    11. Mediterranean Diet
      1. Fung (2009) Circulation 119(8): 1093-1100 [PubMed]
    12. Weight loss
      1. Increased waist to hip ratio (Apple Obesity) is associated with an increased CVA risk (OR 1.65)
    13. Obstructive Sleep Apnea
      1. Present in 50-70% of patients with prior stroke or TIA
  4. Ineffective measures
    1. Homocysteine modification with Vitamins not effective
      1. Toole (2004) JAMA 291:565-75 [PubMed]

V. References

  1. (2015) Presc Lett 22(9): 53
  2. Lyden (2001) CMEA Medicine Lecture, San Diego
  3. Lyden (1998) CMEA Medicine Lecture, San Diego
  4. Adams (2007) Stroke 38(5): 1655-711 [PubMed]
  5. Beauchamp (1999) Radiology 212(2):307-24 [PubMed]
  6. Dickerson (2007) Am Fam Physician 76(3):382-8 [PubMed]
  7. Kernan (2014) Stroke 45(7): 2160-236 [PubMed]
  8. Kleindorfer (2021) Stroke 52(7):e364-7 +PMID: 34024117 [PubMed]
  9. Ingall (2000) Postgrad Med 107(6):34-50 [PubMed]
  10. Loza (2017) Am Fam Physician 96(7): 436-40 [PubMed]
  11. Sacco (2000) Arch Intern Med 160(11):1579-82 [PubMed]
  12. Simmons (2012) Am Fam Physician 86(6): 527-32 [PubMed]
  13. Solenski (2004) Am Fam Physician 69:1691-8 [PubMed]

Images: Related links to external sites (from Bing)

These images are a random sampling from a Bing search on the term "Prevention of Ischemic Stroke." Click on the image (or right click) to open the source website in a new browser window. Search Bing for all related images

Related Studies

Related Topics in Prevention

advertisement