Secondary Stroke Prevention
SUMMARY:
Each year, roughly one million Americans experience a stroke or transient ischemic attack (TIA). Nearly 25% of strokes each year are recurrent, occurring in patients who have already experienced a prior stroke. Patients who have suffered one stroke are more at risk of suffering another, and so preventing secondary strokes is a cornerstone of post-stroke care. Repeated strokes can lead to increased risk of dementia, disability, and increased mortality. The American Heart Association/American Stroke Association have put together a guideline with recommendations for the prevention of secondary stroke.
Diagnostic Evaluation
- For patients who present with stroke or TIA, diagnostic evaluation should include
- EKG, to screen for arrhythmia or cardiomyopathy
- CT +/- MRI brain
- Bloodwork: CBC | PT/INR | Glucose | A1c | Lipid panel | Creatinine
- In cases of symptomatic anterior circulation cerebral infarct, carotid arteries should be evaluated for revascularization targets
- CTA | MRA | Carotid US
- In patients with cryptogenic stroke work up also includes
- Cardiac echocardiography
- Cardiac CT/MRI in some cases (e.g., Embolic stroke unknown source)
- Long-term rhythm monitoring (e.g., Implantable loop recorder | Holter monitor) IF patient has no contraindication to anticoagulation
- In the appropriate clinical context, consider obtaining further testing (e.g., Hypercoagulable testing | Lumbar puncture | Infectious studies | Drug use screen | Systemic inflammatory markers)
- CTA | MRA
- In patients with stroke or TIA and negative initial brain imaging, follow up CT or MRI may be obtained to confirm diagnosis
- For patients with ischemic stroke, diagnostic work up should be done soon after stroke is diagnosed, ideally completed with 48 hours of stroke symptoms
Stroke Subtypes
Hemorrhagic Stroke
- Intracerebral hemorrhage
- Subarachnoid hemorrhage
Ischemic Stroke
- Lacunar stroke
- Most, but not all, lacunar strokes are due to small vessel disease
- Cardioembolic
- Left atrial thrombus | Left ventricular thrombus
- Atrial fibrillation | Atrial flutter
- Cardiomyopathy
- Valvular disease (e.g., Bioprosthetic/mechanical heart valve | Rheumatic valve disease)
- Endocarditis
- Atrial Myxoma
- Cryptogenic
- Embolic stroke unknown source (ESUS): Diagnosed when no source of stroke is found despite extensive work up (e.g., Arterial imaging | Echocardiography | Extended rhythm monitoring | Lipid panel | A1c)
- Non-ESUS: A stroke of unclear origin that does not appear to have been embolic
- Large Artery
- Carotid artery disease
- Extracranial vertebral artery stenosis
- Arterial dissection
Modifiable Risk Factors
- Management of vascular risk factors is critically important for reduction of secondary stroke risk
- The vast majority (up to 90%) of strokes can be prevented by focusing on risk factor modification
- Addressing multiple risk factors has additive benefits for stroke risk reduction
- Vascular risk factors include
- Diabetes: Goal A1c ≤ 7% for most patients | GLP-1 and SGLT2-inhibitors preferred agents depending on co-morbid conditions (See “Related Topics” below for more information)
- Hypertension: Thiazides and ARB/ACE-I specifically recommended for blood pressure control and reducing stroke risk | Goal BP <130/80
- Hyperlipidemia: High intensity statin (e.g., Atorvastatin 80mg daily) | Add therapy as needed for high-risk patients or those with persistent LDL ≥70 mg/dL (e.g., Ezetimibe | PCSK-9 inhibitor)
- Hypertriglyceridemia: Icosapent Ethyl 2g twice daily for select patients
- Tobacco use: Smoking cessation | Avoidance of environmental tobacco smoke
- Lifestyle changes, with the assistance of a multidisciplinary team, should also be implemented to decrease modifiable risks including
- Healthy diet: Low salt (e.g., Reduction of salt intake to 1.5g/day) | Mediterranean diet
- Physical activity: Moderate intensity aerobic activity for ≥10 minutes four times a week | Vigorous intensity aerobic activity for ≥20 minutes two times a week | Break up sedentary time with short standing or light exercise intervals every 30 minutes
- Reduce or eliminate alcohol consumption
- Avoid illicit drug use (e.g., Stimulants | IV drug use)
- Treatment and screening for obstructive sleep apnea
Anti-Thrombotic and Invasive Therapy
- Antithrombotic therapy, including antiplatelet or anticoagulant agents, is recommended for nearly all patients following ischemic stroke
- Contraindications to anticoagulation include: High risk of bleeding | Large infarctions | Continued hemorrhagic conversion | Uncontrolled elevated blood pressure
- In patients with non-cardioembolic ischemic TIA or stroke, antiplatelet therapy is preferred over oral anticoagulation to minimize risk of bleeding
- ASA (50 to 325mg daily) should be started in all ischemic non-cardioembolic stroke and TIA patients
- Clopidogrel (Plavix) should be added for dual antiplatelet therapy (DAPT) in cases of high-risk TIA or minor stroke (NIHSS ≤3) (defined as an ABCD2 score of ≥4) and continued for 21 to 90 days
- Ticagrelor (Brilinta) can be considered in place of Clopidogrel (Plavix) for a 30-day course in patients with: Minor to moderate stroke (NIHSS ≤5) | High risk TIA (ABCD2 score ≥6) | Symptomatic intra/extra-cranial stenosis ≥30% in an artery which may have caused the event
Cardioembolic stroke
- In patients with TIA or stroke AND nonvalvular atrial fibrillation or atrial flutter, oral anticoagulation (e.g., Apixaban (Eliquis) | Rivaroxaban (Xarelto) | Warfarin (Coumadin) is recommended to reduce risk of recurrent stroke
- This recommendation is regardless of if the atrial fibrillation is permanent, persistent, or paroxysmal
- In the absence of a moderate – severe mitral stenosis or a mechanical heart valve, a direct oral anticoagulation e.g., Apixaban (Eliquis) | Rivaroxaban (Xarelto) | Dabigatran (Pradaxa) | Edoxaban (Lixiana) is recommended over Warfarin (Coumadin)
- Anticoagulation post stroke should begin within 2 to 14 days of the initial event, though patients with TIA and atrial fibrillation/flutter may start anticoagulation immediately
- Patients at high risk of hemorrhagic conversion may delay starting anticoagulation for at least 14 days post stroke
- Apixiban and Warfarin are preferred for ESRD patients
- Direct oral anticoagulants (DOACs) are recommended over warfarin for cancer patients with Atrial fib/flutter and TIA or stroke
- Warfarin is preferred for patients with valvular atrial fibrillation/flutter
- Patients with endocarditis and TIA or stroke should undergo surgery for removal of vegetations if they have: Recurrent emboli AND persistent vegetations despite antibiotic therapy | Mobile vegetations >10mm | Other indications for valve surgery
- In stroke patients with LV thrombus, anticoagulation with therapeutic warfarin is recommended for at least 3 months
- Warfarin for 3 months is additionally recommended if the patient has left atrial thrombus in the setting of cardiomyopathy
- Determining which cardioembolic stroke patients with a patent foramen ovale (PFO) would benefit from PFO closure is a complicated process that should involve neurologists and cardiologists
Large artery stroke
- In patients with stroke or TIA caused by 50 to 90% stenosis of a major intracranial artery, ASA 325mg/d is recommended to reduce risk of recurrent stroke and vascular death
- For patients with recent stroke (within the last 30 days) and severe stenosis (70 to 99%) providers can add Clopidogrel (Plavix) 75mg/d to ASA 325mg/d for 90 days to further reduce risk
- In patients within 24 hours of a minor stroke OR high-risk TIA with concomitant ipsilateral stenosis (>30%) of a major intracranial artery, the addition of Ticagrelor (Brilinta) 90mg twice daily to ASA 325mg/d for 30 days can be considered
- In patients with 50 to 99% stenosis of a major intracranial artery, the addition of Cilostazol 200mg/d in addition to ASA or Clopidogrel can be considered
- Angioplasty and stenting of stenosis of major intracranial arteries is generally not recommended
- In patients with TIA or non-disabling stroke within the past 6 months, and ipsilateral severe (70 to 90%) stenosis of the carotid artery, carotid endarterectomy (CEA) is recommended for patients with low (<6%) surgical risk
- This is in addition to risk factor modification and antiplatelet therapy
- CEA is also recommended in patients with more moderate stenosis (50 to 69%)
- Surgery should be performed within 2 weeks of the index event
- Carotid artery stent (CAS) may be considered for patients at higher surgical risk
Cryptogenic
- In patients with ESUS, initiating anticoagulation is not recommended
- Patients with cryptogenic stroke are otherwise treated with antiplatelet therapy as outlined above for non-cardioembolic ischemic stroke or TIA
Special populations
- Sickle cell anemia
- Patients with sickle cell anemia and prior ischemic stroke or TIA should receive chronic blood transfusions to reduce Hgb S to <30% of total hemoglobin
- Caution is advised when considering antithrombotics for secondary stroke prevention in patients with SCD because the stroke mechanism is less certain and patients with SCD are also at higher risk for hemorrhagic stroke. If there is evidence for other stroke mechanisms in a patient with SCD (ie, atherosclerosis), then reasonable to administer antithrombotics
- If unable to access blood transfusions, Hydroxyurea may be used to lower stroke risk
- Autoimmune vasculitis
- In patients with autoimmune vasculitis (e.g., Giant cell arteritis | Primary CNS angiitis) and stroke, high dose steroids should be started immediately to reduce future risk of stroke
- Infectious vasculitis
- Patients with ischemic stroke or TIA with infectious vasculitis (e.g., Varicella cerebral vasculitis | Neurosyphilis | Bacterial meningitis) should have treatment focused on treating the underlying infection
- APLS, Moya Moya
Health Equity
- As we continue to study about healthcare disparities, many guidelines have been updated to include a focus on health equity when considering treatment and management of a patient’s medical problems
- For patients following stroke and TIA, evaluating and addressing social determinants of health is recommended
- This includes: Literacy level | Language proficiency | Medication affordability | Access to housing | Food insecurity | Transportation barriers
KEY POINTS:
- Patients who have suffered a stroke or TIA are at increased risk of repeat stroke and vascular death
- The vast majority of secondary strokes can be prevented by focusing management on vascular risk factors and lifestyle modifications
- The main contributors to secondary stroke risk are abdominal obesity, hypertension, diet, tobacco use, and physical inactivity
- Antithrombotic, either antiplatelet or anticoagulation, therapy is recommended for nearly all post-stroke patients absent any contraindications
