What pharmacological agents are recommended for secondary prevention of stroke in a patient with a history of stroke?

Secondary Prevention of Stroke: Pharmacological Management

For secondary prevention of stroke, antiplatelet therapy is recommended for all patients with ischemic stroke or TIA who are not candidates for anticoagulation, with options including aspirin (75-325 mg daily), clopidogrel (75 mg daily), or aspirin plus extended-release dipyridamole (25/200 mg twice daily). 1

Antiplatelet Therapy for Non-Cardioembolic Stroke

First-line Options

• Single Antiplatelet Therapy (SAPT):
  • Aspirin (75-325 mg daily)
  • Clopidogrel (75 mg daily)
  • Aspirin (25 mg) plus extended-release dipyridamole (200 mg) twice daily

The selection should be based on patient-specific factors including comorbidities, risk of bleeding, and drug interactions 1.

Special Situations - Dual Antiplatelet Therapy (DAPT)

For patients with minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4):

• Short-term DAPT with aspirin 81 mg daily and clopidogrel 75 mg daily should be initiated as early as possible (ideally within 12-24 hours of symptom onset)
• Start with loading doses: aspirin (160-325 mg) and clopidogrel (300-600 mg)
• Continue DAPT for 21 days only
• Follow with long-term single antiplatelet therapy 1

For patients with mild-moderate ischemic stroke (NIHSS ≤5) or high-risk TIA:

• Alternative DAPT option: aspirin (75-100 mg daily) and ticagrelor (90 mg twice daily)
• Continue for 30 days only
• Follow with long-term single antiplatelet therapy 1

Intracranial Atherosclerotic Disease

• For patients with symptomatic intracranial stenosis (50-99%), dual antiplatelet therapy is appropriate medical therapy 1
• Target systolic blood pressure <140 mmHg
• High-dose statin therapy is recommended 1, 2

Anticoagulation Therapy

Anticoagulation is indicated for:

• Atrial fibrillation
• Mechanical prosthetic heart valves
• Cardioembolic stroke from valvular heart disease 1, 2

For patients with mechanical prosthetic heart valves:

• Warfarin with INR target of 3.0 (range 2.5-3.5) 1

For patients with embolic stroke of undetermined source (ESUS):

• Antiplatelet therapy is recommended, not anticoagulation 1

Additional Pharmacological Strategies

Blood Pressure Management

• Target BP <130/80 mmHg for most patients
• For intracranial stenosis, maintain systolic BP <140 mmHg 1, 2

Lipid Management

• High-intensity statin therapy for all stroke patients 2

Glucose Management

• Monitor and manage glucose according to national diabetes guidelines 2

Important Caveats and Pitfalls

1. Avoid long-term dual antiplatelet therapy beyond the recommended short-term period (21-30 days) as it increases bleeding risk without additional benefit 1, 2

2. Do not use full-intensity parenteral anticoagulation with unfractionated heparin or low-molecular-weight heparinoids for patients with extracranial cerebrovascular atherosclerosis who develop TIA or acute ischemic stroke 1

3. Avoid combination of clopidogrel and aspirin beyond 3 months after stroke or TIA due to increased bleeding risk 1

4. For recurrent stroke while on antiplatelet therapy:

   • Reassess all vascular risk factors and stroke etiology
   • If stroke occurs while on aspirin, consider switching to clopidogrel
   • If stroke occurs while on clopidogrel, consider switching to aspirin plus extended-release dipyridamole 1

5. For patients with intracerebral hemorrhage who were previously on antithrombotics, all anticoagulants and antiplatelets should be discontinued for at least 1-2 weeks 2

Algorithm for Selecting Antiplatelet Therapy

1. Determine stroke etiology:

   • Non-cardioembolic stroke → Antiplatelet therapy
   • Cardioembolic stroke → Anticoagulation

2. For non-cardioembolic stroke:

   • If minor stroke (NIHSS ≤3) or high-risk TIA within past 24 hours → Short-term DAPT (21-30 days) followed by SAPT
   • For all other non-cardioembolic strokes → SAPT with one of the three first-line options

3. For intracranial stenosis:

   • DAPT for up to 90 days, then SAPT
   • Aggressive blood pressure and lipid management

This evidence-based approach to secondary stroke prevention prioritizes reducing morbidity and mortality while maintaining quality of life through appropriate pharmacological management.