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Stroke Prevention - Comprehensive CNS Knowledge

Overview

• Primary prevention - reducing risk in people who have never had a stroke
• Secondary prevention - preventing recurrence in those who have already had a stroke or TIA

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1. RISK FACTORS FOR STROKE

Non-Modifiable Risk Factors

• Age - risk increases sharply after 55; doubles each decade thereafter
• Sex - men have slightly higher overall risk; women live longer and have more lifetime events
• Race/Ethnicity - Black Americans have nearly double the risk of white Americans; higher rates of hypertension and diabetes
• Genetics/Family history - first-degree relative with stroke increases risk
• Prior stroke or TIA - the single strongest predictor of future stroke (recurrence ~4% at 90 days, ~5% at 1 year)

Modifiable Risk Factors (the targets of prevention)

• Adams and Victor's Principles of Neurology, 12th Ed. - "It is now a major goal of general medicine to reduce the incidence of modifiable risk factors for stroke (primary prevention) by addressing hypertension, smoking, glucose control, and lipid lowering."

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2. PRIMARY STROKE PREVENTION

A. Hypertension Control (MOST IMPORTANT modifiable risk factor)

• Target BP: <130/80 mmHg in high-risk patients
• Preferred agents post-stroke: thiazide-like diuretics (especially indapamide), ACE inhibitors, angiotensin receptor blockers (ARBs)
• Lowering BP to <130/80 mmHg after lacunar infarction specifically reduces risk of subsequent hemorrhagic stroke
• Benefit is proportional to the degree of BP reduction
• Goldman-Cecil Medicine highlights that drug therapy is usually initiated when BP exceeds 140/90 mmHg in high-risk individuals

B. Diabetes Management

• Tight glycemic control reduces microvascular risk
• Target HbA1c individualized; avoid hypoglycemia (harmful in acute stroke)
• Control of diabetes also reduces cardiovascular coexisting risk

C. Lipid Management (Statins)

• High-intensity statins are recommended for patients aged <75 years without safety concerns:
  • Atorvastatin 40-80 mg or Rosuvastatin 20-40 mg
• Moderate-intensity for >75 years or concerns:
  • Atorvastatin 10-20 mg, Rosuvastatin 5-10 mg, Simvastatin 20-40 mg
• Washington Manual of Medical Therapeutics - BP reduction even in normotensive stroke patients is beneficial; statins are a key component of the "BLASTED" secondary prevention bundle

D. Smoking Cessation

• Smoking doubles stroke risk; cessation reduces risk within 2 years
• Should be offered as part of a multi-disciplinary stroke prevention program (smoking cessation counseling integrated with PT/OT/ST)

E. Physical Activity and Weight

• Regular moderate aerobic exercise (150 min/week) reduces BP, glucose, and cardiovascular risk
• BMI target <25 kg/m²

F. Atrial Fibrillation Screening and Anticoagulation

CHA2DS2-VASc Scoring System

HAS-BLED Score (Bleeding Risk Assessment)

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3. ANTICOAGULATION - CHOICE OF AGENT

DOACs (First-Line - Recommended over Warfarin)

• Easier dosing (no INR monitoring required)
• Fewer drug/food interactions
• Lower risk of intracranial hemorrhage

• Dabigatran: Idarucizumab (monoclonal antibody)
• Factor Xa inhibitors: Andexanet alfa
• Note: Vitamin K, FFP, and PCC are generally ineffective for DOAC reversal

Warfarin (Vitamin K Antagonist)

• Still viable when DOACs are not tolerated or in specific settings (e.g., mechanical heart valves, severe mitral stenosis)
• Requires regular INR monitoring (target 2.0-3.0)
• Monitor more carefully in renal impairment (CKD stages G4-G5)

Special Populations

• CKD Stage G3: DOACs are safe and effective; warfarin can be used per general guidelines
• Dialysis patients: Significant uncertainty; apixaban (2.5 mg BID) has FDA approval but is based on limited trial data; individual decision-making required
• Elderly patients: Despite higher bleeding risk, anticoagulation still reduces net harm if carefully selected (stroke risk typically outweighs bleeding risk)

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4. ANTIPLATELET THERAPY

• For patients with CKD/ESKD: ASA alone is preferred per American Stroke Association guidelines; agent selection is based on individual risk factor evaluation

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5. SECONDARY STROKE PREVENTION - The "BLASTED" Mnemonic

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6. CAROTID ARTERY DISEASE AND REVASCULARIZATION

• Carotid Endarterectomy (CEA) is indicated for symptomatic carotid stenosis >70%
• May be considered for 50-69% symptomatic stenosis at high-risk centers
• Benefits are greatest when performed within 2 weeks of the TIA or stroke
• Carotid artery stenting (CAS) is an alternative in high surgical-risk patients

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7. LEFT ATRIAL APPENDAGE OCCLUSION (LAAO)

• Mechanical alternative to long-term anticoagulation in patients with AF who cannot tolerate anticoagulants
• Devices (e.g., Watchman) close off the LAA where 90% of AF thrombi originate
• Post-procedure: anticoagulation for 1-2 months, then dual antiplatelet therapy for 6 months, then aspirin monotherapy
• Recent systematic review in JAHA (2024) comparing LAAO vs. oral anticoagulants confirms it as a viable alternative in selected patients

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8. OBSTRUCTIVE SLEEP APNEA (OSA)

• OSA is an independent, under-recognized stroke risk factor
• Causes hypertension, atrial fibrillation, endothelial dysfunction
• CPAP therapy reduces recurrent stroke risk
• All post-stroke patients should be screened for OSA

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9. HORMONAL THERAPY AND STROKE RISK

• Combined oral contraceptives (especially estrogen-containing, >50 mcg ethinyl estradiol): increase stroke risk ~2x
• Should be discontinued in women who have a stroke
• Progestin-only preparations are acceptable in most cases
• Hormone replacement therapy in postmenopausal women: unclear net BP effect; avoid if poorly controlled BP

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10. LIFESTYLE AND DIETARY MODIFICATIONS

• DASH or Mediterranean diet - reduce cardiovascular and cerebrovascular risk
• Salt restriction - reduces BP and intensity of antihypertensive drug therapy needed
• Alcohol - moderate consumption (1 drink/day) may be neutral or mildly protective; heavy drinking increases hemorrhagic stroke risk
• Regular aerobic exercise - 150 minutes of moderate-intensity per week
• Dairy consumption - a 2025 meta-analysis in Nature Communications (PMID: 39762253) found associations between dairy intake and incident cardiovascular disease; individualized dietary guidance remains important

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11. REHABILITATION AS PART OF PREVENTION

• Physical therapy (PT) - mobility, fall prevention
• Occupational therapy (OT) - ADL retraining
• Speech therapy (ST) - aphasia, dysphagia management
• Stroke educator - medication adherence, lifestyle counseling
• Smoking cessation counseling - formal support programs

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12. RECENT EVIDENCE UPDATE (2025)

• A 2025 systematic review in JAMA (PMID: 40136306) confirmed that after a TIA or minor stroke, long-term stroke risk remains significant - reinforcing the importance of aggressive secondary prevention.
• A 2025 systematic review in JNNP (PMID: 40180437) identified key modifiable risk factors for stroke and dementia, supporting aggressive multi-risk-factor management particularly targeting hypertension, physical inactivity, and diabetes.

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Summary - Key Prevention Targets

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