ischemic%20stroke
ISCHEMIC STROKE
Ischemic stroke occurs when a blood vessel supplying the brain is obstructed.
Consider stroke in any patient presenting with sudden focal neurological deficit or any alteration in level of consciousness.
Rapid evaluation is essential for sure of time-sensitive treatments.
Determine if patient's symptoms are due to stroke and exclude stroke mimics (eg migraine, hypertensive encephalopathy, hypoglycemia, seizures or post-ictal paresis); identify other conditions requiring immediate intervention and determine the potential causes of stroke.

Prevention

Secondary Prevention

Pharmacological therapy

Antiplatelets

  • Long-term antiplatelet therapy reduces the risk of serious vascular events (eg recurrent stroke, myocardial infarction [MI] or vascular death) following ischemic stroke or transient ischemic attack (TIA)
  • Studies have shown that each of these antiplatelet agents are effective for secondary prevention of stroke
  • Choice of agent is based on relative effectiveness, patient characteristics and preferences, safety, cost, risk factors, tolerability, potential for drug interactions
  • Aspirin
    • Most widely studied antiplatelet agent
    • Benefits of Aspirin therapy to long-term preventive therapy of stroke are well established
    • Therapy with Aspirin alone or in combination with Clopidogrel is recommended in patients with stroke or transient ischemic attack with paroxysmal (intermittent) or permanent atrial fibrillation who are unable or refuse to take oral anticoagulants
  • Aspirin/Dipyridamole
    • Combination of Aspirin and Dipyridamole may be superior to aspirin alone in the secondary prevention of stroke
    • Less well tolerated than Aspirin and Clopidogrel mainly because of headache
  • Clopidogrel
    • May be used as 1st-line agent in patients unable to tolerate Aspirin and Dipyridamole
    • Associated with fewer gastrointestinal and central nervous system events including gastric and intracranial hemorrhage, but slightly more frequent skin rash and diarrhea compared with Aspirin
  • Aspirin/Clopidogrel
    • Combination may be used in patients with acute coronary syndrome
    • Has additional efficacy compared with Aspirin monotherapy in reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage among patients with minor ischemic stroke or transient ischemic attack
    • May be also used in stroke prevention among atrial fibrillation patients who refuse any form of oral anticoagulants (OAC) or those unable to tolerate oral anticoagulants for reasons not related to bleeding
    • Less effective than Warfarin in stroke prevention of patients with nonvalvular atrial fibrillation
  • Cilostazol
    • A phosphodiesterase-3 inhibitor used as one of the treatment options in patients with a history of non-cardioembolic ischemic stroke or transient ischemic attack
    • Some studies have shown its efficacy and safety in secondary stroke prevention among Asians with peripheral arterial disease
  • Ticlopidine
    • Shown to be effective for the prevention of vascular outcomes in patients with cerebrovascular disease
    • Rates of gastrointestinal bleeding are comparable or less than with Aspirin
    • Associated with thrombotic thrombocytopenic purpura, aplastic anemia, neutropenia, agranulocytosis
  • Triflusal
    • Has been shown to be non-inferior to Aspirin in patients with stroke/myocardial infarction/vascular death and with less risk of hemorrhagic complications
    • Combination with Acenocoumarol is more effective in reducing risk of stroke in patients with nonvalvular atrial fibrillation than Acenocoumarol monotherapy

Oral Anticoagulants

  • It is reasonable to initiate oral anticoagulation within 14 days after the onset of neurological symptoms for most patients with a stroke or transient ischemic attack with low risk of hemorrhagic conversion in the setting of atrial fibrillation
    • May delay initiation of oral coagulation beyond 14 days if there is a high risk for hemorrhagic conversion (ie large infarct, hemorrhagic transformation on initial imaging, uncontrolled hypertension or hemorrhagic tendency)
  • Recommended for patients with moderate to high risk of atrial fibrillation-associated stroke (CHA2DS2-VASc1 score = 1 not due to female gender;  CHA2DS2-VASc1 score ≥2) without recent unprovoked bleeding or intracerebral hemorrhage
  • It is reasonable for patients with atrial fibrillation and a history of stroke or transient ischemic attack who needs to temporarily interrupt oral anticoagulation therapy to have a bridging therapy with a low molecular weight heparin (or equivalent anticoagulant agent if intolerant to Heparin), depending on perceived risk for thromboembolism and bleeding

Secondary prevention in select patients

  • Apixaban
    • A direct and competitive factor Xa inhibitor, indicated for the prevention of 1st and recurrent stroke in patient with nonvalvular atrial fibrillation
    • Alternative to Aspirin in patients with nonvalvular atrial fibrillation deemed unsuitable for vitamin K antagonist with similar bleeding risk as that of Aspirin
    • Alternative to Warfarin in nonvalvular atrial fibrillation patients deemed appropriate for vitamin K antagonist therapy
    • A dose of 5 mg twice daily is given for those who have ≥1 additional risk factor and no more than one of the following characteristics: Age ≥80 years, weight ≤60 kg, serum creatinine ≥1.5 mg/dL
      • Above dose is more effective than Aspirin or Warfarin in patients with nonvalvular atrial fibrillation with moderate risk for embolism; risk of intracerebral hemorrhage is low
      • Dose is halved (2.5 mg twice daily) for those who have ≥2 of the above characteristics
  • Dabigatran
    • A direct thrombin inhibitor approved for the prevention of first and recurrent stroke and of systemic thromboembolism in patients with nonvalvular atrial fibrillation (AF) and at least 1 additional risk factor
      • Recommended in atrial fibrillation patients who are at intermediate (CHADS2 score = 1) to high risk (CHADS2 score = 2) of stroke/systemic embolism
        • CHA2DS2 score represents an individual’s risk for stroke based on the presence of coexistent medical conditions (eg congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack)
    • A study conducted in >18,000 patients with atrial fibrillation showed that Dabigatran, given at a dose of 150 mg twice daily, showed lower rates of stroke or systemic embolism and less frequent intracerebral hemorrhage (but with similar rates of major bleeding) compared with Warfarin
    • Dabigatran given at 110 mg 2x a day had similar rates of stroke as Warfarin but with significantly less major bleeding
  • Rivaroxaban
    • A factor Xa inhibitor recommended for the prevention of first and recurrent stroke in patients with nonvalvular atrial fibrillation who are at moderate to high risk of stroke (prior history of transient ischemic attack, stroke or systemic embolization or ≥2 additional risk factors)
      • As effective as Warfarin in preventing cerebral or systemic embolism in patients with nonvalvular atrial fibrillation but has a lower risk of intracranial bleeding
  • Vitamin K Antagonist
    • Indicated for the prevention of recurrent stroke in patients with nonvalvular atrial fibrillation
    • A target INR of 2.5 is recommended in patients with ischemic stroke or transient ischemic attack with paroxysmal, persistent or permanent atrial fibrillation
  • Warfarin
    • Recommended for use in patients with atrial fibrillation, mechanical prosthetic heart valves and/or other potential sources of cardioembolism
    • Patients with large cardioembolic stroke may start Warfarin 2 weeks from stroke event because of risk of hemorrhagic transformation
    • Risk of serious cerebral hemorrhage; close monitoring is required
    • Combination with antiplatelet therapy is not recommended for all patients after ischemic stroke or transient ischemic attack but is reasonable in patients with clinically apparent coronary artery disease

Antihypertensive Agents

  • Choice of antihypertensives and target blood pressure level should be individualized; average reduction of 10/5 mmHg has been shown to be beneficial with reduction of stroke by 30-40%
  • Blood pressure of <140/90 mmHg has been defined by current guidelines as normal

Antihyperlipidemic Agents

  • Statins
    • Patients already on statins at the time of stroke should continue taking them
      • Administration of statins 48 hours after occurrence of stroke is safe
    • Recommended to reduce the risk of stroke and cardiovascular events for patients with ischemic stroke or transient ischemic attack who have evidence of atherosclerosis, an LDL level of ≥2.6 mmol/L ( ≥100 mg/dL) and with no known coronary heart disease (CHD)
    • Goal in patients with atherosclerotic ischemic stroke or transient ischemic attack and without known coronary heart disease is ≥50% reduction in LDL or a target LDL of <1.8 mmol/L (<70 mg/dL) to achieve maximum benefit
  • Other Drugs
    • May be administered to patients who do not tolerate statins
    • Patients with hypertriglyceridemia or low HDL levels may be treated with Niacin or Gemfibrozil
    • Fibrates should be strongly considered in patient with severe hypertriglyceridemia
      • Fibrates lower triglyceride levels by 30-50% and may increase HDL cholesterol
      • Fenofibrates are the preferred fibrates to use in combination with a statin since they have a lower risk of causing myopathy
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