ischemic%20stroke
ISCHEMIC STROKE
Treatment Guideline Chart
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.

Ischemic%20stroke Management

Prevention

PRIMARY PREVENTION

Lifestyle Modification

  • Consumption of diet rich in fruits and vegetables, and low in fat (especially saturated fat) and sodium
  • Weight loss for overweight or obese patients
  • Regular aerobic exercise ≥30 minutes/day or >150 minutes/week, on most days of the week, depending on patient’s level of fitness  
  • Moderate intake of alcohol for those who drink alcohol
    • Limit to <1 drink/day

Smoking Cessation

  • Smoking is a major independent risk factor for ischemic stroke
  • Advise patient to quit smoking and avoid passive or environmental tobacco smoke
    • Smoking cessation is a significant factor for both primary and secondary prevention of stroke
  • Intervention initiation should be considered which incorporates behavioral and pharmacological support

Hypertension

  • Regular BP monitoring is recommended
  • Lifestyle modification is advised for patients with BP of 130-139/80-89 mmHg and are reassessed after 3-6 months
  • Cardiovascular disease risk stratification is warranted to maximize treatment regimen
  • Hypertensive elderly >80 years of age should be treated

Diabetes Mellitus

  • More stringent BP control and HbA1c targets are important to prevent stroke
    • Target BP <130/80 mmHg, if tolerated SBP <120 mmHg

Dyslipidemia

  • Stratify patient's risk and follow guideline-recommended target levels and lipid-lowering therapy


SECONDARY PREVENTION

  • Includes interventions aimed at preventing recurrent stroke, eg healthy diet, increased physical activity, reduction/elimination of alcohol consumption and intensive medical management of vascular risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking cessation)

Antiplatelets

  • Long-term antiplatelet therapy reduces the risk of serious vascular events (eg recurrent stroke, myocardial infarction or vascular death) following ischemic stroke or transient ischemic attack
  • 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 alone, Dipyridamole plus Aspirin, or Clopidogrel alone is recommended for prevention in patients with non-cardioembolic ischemic stroke or transient ischemic attack
  • Not recommended in cases of non-valvular atrial fibrillation stroke prevention

Aspirin

  • Most widely studied antiplatelet agent
  • Benefits of Aspirin in the long-term preventive therapy of non-cardioembolic stroke are well established

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 recurrent stroke in the first 90 days and does not increase the risk of hemorrhage among patients with minor ischemic stroke or transient ischemic attack when given for 21 days
  • 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
  • Can be an option for patients with recurrent stroke symptoms despite Aspirin use
  • 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


Secondary prevention in select patients


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) in the setting of atrial fibrillation
  • Recommended in patients with cardioembolic ischemic stroke or transient ischemic attack 
  • 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

Apixaban

  • A direct and competitive factor Xa inhibitor indicated for the prevention of 1st and recurrent stroke as well as systemic embolism in patients 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 anticoagulant 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 1st and recurrent stroke and of systemic thromboembolism in patients with nonvalvular atrial fibrillation and at least 1 additional risk factor
    • Recommended in atrial fibrillation patients who are at intermediate to high risk (CHADS2 score1 ≥1) of stroke/systemic embolism
  • 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

Edoxaban

  • A factor Xa inhibitor recommended for the prevention of 1st and recurrent stroke and systemic embolism in patients with nonvalvular atrial fibrillation
  • Requires initial therapy with parenteral anticoagulants prior to starting therapy
  • Kidney function should be assessed prior to administration
    • High creatinine clearance (>95 mL/min) may decrease efficacy
  • Sudden discontinuation increases the ischemic event risks

Rivaroxaban

  • A factor Xa inhibitor recommended for the prevention of 1st and recurrent stroke and systemic embolism 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 2-3 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, and also for stroke prevention in patients with nonvalvular atrial fibrillation
  • 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%
    • ACE inhibitor, angiotensin II receptor blocker or a thiazide diuretic helps reduce the risk of recurrent stroke in patients with hypertension
  • Blood pressure of >140/90 mmHg has been defined by current guidelines as reasonable threshold to improve long-term control in neurologically stable patient
  • Please see Hypertension disease management chart for further information

Antihyperlipidemic Agents

Statins

  • Patients already on statins at the time of stroke should continue taking them
  • Recommended to reduce the risk of stroke recurrence in patients with ischemic stroke and an LDL level of ≥2.6 mmol/L (≥100 mg/dL) without known coronary heart disease or major cardiac sources of embolism
  • High-intensity statin and, if needed, Ezetimibe and a PCSK-9 inhibitor are recommended in patients with ischemic stroke or transient ischemic attack and atherosclerotic disease to achieve a goal LDL-C of <1.8 mmol/L (<70 mg/dL) in order to decrease the risk of major cardiovascular events 
  • Please see Dyslipidemia disease management chart for further information

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

Antidiabetic Agents

  • Glucose-lowering medications with proven cardiovascular benefit (eg GLP-1 receptor agonist, SGLT2 inhibitor) should be used to treat diabetes in patients with ischemic stroke or transient ischemic attack with diabetes to decrease the risk of major adverse cardiovascular events 
  • Please see Diabetes Mellitus disease management chart for further information

Smoking Cessation

  • Counseling with or without pharmacotherapy (eg Bupropion, Varenicline or nicotine replacement) is recommended to patients with stroke or transient ischemic attack who smoke to help them stop smoking 
  • Please see Smoking Cessation disease management chart for further information

1CHA2DS2-VASc score represents the individual risk for the stroke based on age ≥75, presence of vascular disease and increased risk of stroke among patients with atrial fibrillation

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