What are the medical treatments for secondary prevention of stroke?

Secondary Prevention Medical Treatment for Stroke

For patients with noncardioembolic ischemic stroke or TIA, antiplatelet therapy is the cornerstone of secondary prevention, with short-term dual antiplatelet therapy (DAPT) followed by long-term single antiplatelet therapy (SAPT) being the most effective approach for reducing recurrent stroke risk. 1

Antiplatelet Therapy

Initial Treatment Strategy

• For patients with recent (within 24 hours) minor to moderate stroke (NIHSS ≤5) or high-risk TIA (ABCD2 score ≥4), short-term DAPT with aspirin plus clopidogrel for 21-30 days is recommended to reduce early recurrent stroke risk 1, 2
• Initial loading doses should include aspirin 160-325 mg and clopidogrel 300-600 mg, followed by maintenance doses of aspirin 81 mg daily and clopidogrel 75 mg daily 2
• After the initial 21-30 day DAPT period, patients should transition to long-term SAPT 1, 2
• For patients with severe stenosis (70%-99%) of a major intracranial artery, DAPT with clopidogrel plus aspirin may be continued for up to 90 days 1

Long-term Antiplatelet Options

• Acceptable options for long-term SAPT include:
  • Aspirin (50-325 mg daily) 1
  • Clopidogrel (75 mg daily) 1
  • Combination of aspirin 25 mg and extended-release dipyridamole 200 mg twice daily 1
• Clopidogrel should be used for patients who are intolerant of aspirin or in whom aspirin is contraindicated 1, 3
• Cilostazol (200 mg/day) might be considered as an addition to aspirin or clopidogrel in patients with stroke attributable to 50%-99% stenosis of a major intracranial artery 1

Important Cautions

• Continuous use of DAPT beyond 90 days is associated with increased bleeding risk without additional benefit in stroke reduction 1, 2
• Triple antiplatelet therapy is not recommended due to increased bleeding risk without additional benefit 1
• For patients already taking aspirin at the time of stroke, the effectiveness of increasing the dose or changing to another antiplatelet medication is not well established 1

Anticoagulation Therapy

• Anticoagulation is recommended for patients with ischemic stroke or TIA who have:

  • Atrial fibrillation 1, 2
  • Cardioembolic stroke from valvular heart disease 1
  • Recent myocardial infarction 1
  • Mechanical prosthetic heart valves (warfarin with INR target of 3.0, range 2.5-3.5) 1

• For patients with mechanical prosthetic heart valves who have an ischemic stroke despite adequate anticoagulation, adding aspirin 75-100 mg/day is reasonable if bleeding risk is not high 1

• Anticoagulation is not recommended for patients with noncardioembolic stroke of presumed arterial origin, as there is no evidence of additional benefit over antiplatelet therapy 1

Management of Intracranial Atherosclerosis

• For patients with stroke or TIA caused by 50%-99% stenosis of a major intracranial artery:

  • Aspirin 325 mg/day is recommended over warfarin 1
  • For severe stenosis (70%-99%), adding clopidogrel 75 mg/day to aspirin for up to 90 days is reasonable 1
  • Maintenance of systolic blood pressure below 140 mmHg, high-intensity statin therapy, and at least moderate physical activity are recommended 1

• Angioplasty and stenting should not be performed as initial treatment for patients with severe intracranial stenosis, even for those who were taking an antithrombotic agent at the time of stroke 1

Risk Factor Management

• Blood pressure lowering therapy is recommended for all patients after stroke or TIA, whether normotensive or hypertensive 1, 4
• High-intensity statin therapy is recommended to reduce LDL-C by at least 50% or achieve a target of <70 mg/dL 4, 5
• In the SPARCL trial, atorvastatin 80 mg reduced the incidence of ischemic stroke (9.2% vs 11.6%) compared to placebo, though with a slightly increased risk of hemorrhagic stroke (2.3% vs 1.4%) 5
• Regular physical activity (at least 30 minutes daily of moderate-intensity aerobic exercise) is recommended 4, 2
• Diet modifications should include following a Mediterranean-style diet, reducing salt intake, and limiting alcohol consumption 4, 2
• Smoking cessation is essential for reducing recurrent stroke risk 1, 2

Special Considerations

Carotid Disease

• Carotid endarterectomy is recommended for patients with nondisabling carotid artery territory ischemic stroke or TIA with ipsilateral carotid stenosis measured at 70%-99% (NASCET criteria) 1
• For patients with 50%-69% stenosis, carotid endarterectomy should be considered based on patient factors (age, gender, comorbidities) 1
• Eligible patients should undergo carotid endarterectomy as soon as possible after the event, ideally within 2 weeks 1

Valvular Heart Disease

• For patients with ischemic stroke or TIA who have rheumatic mitral valve disease, long-term warfarin therapy is reasonable with an INR target range of 2.5 (range 2.0-3.0) 1
• For patients with bioprosthetic heart valves with no other source of thromboembolism, anticoagulation with warfarin (INR 2.0-3.0) may be considered 1

Implementation and Follow-up

• A multidisciplinary approach involving neurologists, internists, and primary care physicians is essential for optimizing secondary prevention 4, 2
• Regular monitoring for medication adherence, side effects, and risk factor control is crucial 4
• Implementation of multiple lifestyle changes simultaneously, along with appropriate medication, could reduce the risk of recurrent stroke by up to 80% 4