Secondary Prevention of Ischemic Stroke

Introduction to Secondary Prevention

The American Heart Association recommends aspirin administration within the first 48 hours after an ischemic stroke to prevent 4 recurrent strokes and 5 vascular deaths per 1000 patients treated, with a strength of evidence supporting its use in secondary prevention 1
The American College of Cardiology suggests that atorvastatin 80 mg/day reduces major cardiovascular events by 22% compared to 10 mg/day, highlighting the importance of statin therapy in secondary prevention 2

Aspirin reduces the risk of new vascular events by 25% and total mortality by 10% when administered after an ischemic stroke, according to the American Heart Association, with a moderate strength of evidence supporting its use 2
The European Society of Cardiology recommends aspirin 75-100 mg/day for long-term treatment, with a preference for lower doses (75-100 mg), citing a reduction in bleeding risk 3
Clopidogrel is slightly more effective than aspirin, with a relative risk reduction of 8.7%, as stated by the International Journal of Stroke, and is preferred in patients with non-cardioembolic ischemic stroke or TIA 4, 5
The combination of aspirin and dipyridamole is more effective than aspirin alone, with a relative risk reduction of 18%, according to the International Journal of Stroke, but its use is not universally recommended due to increased bleeding risk 4
Single antiplatelet therapy is recommended, with options including aspirin 75-100 mg daily or clopidogrel 75 mg daily, as suggested by the American College of Chest Physicians, with consideration of patient-specific factors such as gastrointestinal bleeding history and cost concerns 6

The American College of Cardiology recommends atorvastatin 80 mg/day to reduce LDL to a level close to or below 70 mg/dL, with a reduction in major cardiovascular events by 22%, highlighting the importance of aggressive lipid management in secondary prevention 7
The International Journal of Stroke suggests that statin therapy reduces the risk of major cardiovascular events by 22%, with a moderate strength of evidence supporting its use 2

The American Heart Association does not recommend routine anticoagulation in patients with non-cardioembolic ischemic stroke, due to the increased risk of hemorrhagic complications, but suggests its use in patients with atrial fibrillation or other high-risk conditions 2
The International Journal of Stroke suggests that anticoagulation with warfarin is beneficial in patients with non-rheumatic atrial fibrillation and recent ischemic stroke or TIA, with a moderate strength of evidence supporting its use 4

The American Heart Association recommends that all patients after an ischemic stroke or TIA, whether normotensive or hypertensive, should receive therapy to reduce blood pressure, with the initiation of new antihypertensive therapy possibly occurring before discharge or within the first week after the stroke, citing a reduction in recurrent stroke risk 4
The International Journal of Stroke suggests that blood pressure management is crucial in secondary prevention of ischemic stroke, with a moderate strength of evidence supporting its importance 4

The American Heart Association recommends cessation of smoking, with therapy options including nicotine replacement, bupropion, or nortriptiline, partial nicotine receptor agonists, and/or behavioral therapy, citing a reduction in cardiovascular risk 4
The International Journal of Stroke suggests a diet low in fats (especially saturated) and sodium, and high in fruits and vegetables, as well as regular exercise and avoidance of excessive alcohol consumption, with a moderate strength of evidence supporting its importance in secondary prevention 4
The American College of Cardiology recommends early mobilization and adequate hydration to prevent deep vein thrombosis (DVT) and pulmonary embolism (PE), citing a reduction in venous thromboembolism risk 4

The International Journal of Stroke suggests that carotid endarterectomy should be considered in patients with severe carotid stenosis (>70%), with a moderate strength of evidence supporting its use in secondary prevention 4
The American College of Cardiology recommends anticoagulation with warfarin in patients with atrial fibrillation, rather than antiplatelet therapy, citing a reduction in stroke risk 4

The International Journal of Stroke recommends the use of antipyretic therapy (paracetamol and/or physical cooling measures) when fever occurs, as well as the prevention of pressure ulcers and the use of thromboprophylaxis in selected patients, with a moderate strength of evidence supporting its importance in secondary prevention 4
The American Heart Association suggests that early implementation of these pharmacological and non-pharmacological measures significantly reduces morbidity and mortality in post-stroke patients, with quantifiable benefits in terms of reduction of recurrent vascular events and improvement of quality of life, citing a high strength of evidence supporting its use 4
The following table summarizes the bleeding risk profiles of antiplatelet agents:

Agent	Bleeding Risk
Clopidogrel	9.3% (CAPRIE study) [8]
Aspirin	9.3% (CAPRIE study) [8]

Aspirin is associated with an increased risk of gastrointestinal bleeding, and may cause gastric irritation, with a recommended dose of 75-100 mg daily for primary and secondary prevention of cardiovascular disease, as recommended by the American College of Cardiology with a moderate strength of evidence 9
Clopidogrel has a lower risk of gastrointestinal bleeding compared to aspirin, but carries a rare but serious risk of thrombotic thrombocytopenic purpura (TTP), with a high strength of evidence, as recommended by the European Society of Cardiology 10
Continuing DAPT beyond recommended duration increases bleeding without additional benefit, as stated by the European Society of Cardiology, with a high strength of evidence supporting its limited use 11, 12
For patients with high bleeding risk, single antiplatelet therapy rather than dual therapy should be considered, with gastroprotection using proton pump inhibitors, as recommended by the European Society of Cardiology with a moderate strength of evidence 13
P2Y12 inhibitors should be discontinued 5 days (clopidogrel/ticagrelor) or 7 days (prasugrel) before high bleeding risk procedures, as recommended by the European Heart Journal and Anaesthesia with a high strength of evidence 11, 14, 15

For patients with PAD, clopidogrel is the preferred choice due to its strongest evidence for benefit, as recommended by the American College of Chest Physicians with a moderate strength of evidence 16, 9
For patients with cerebrovascular disease, clopidogrel is preferred over aspirin, as recommended by the European Society of Cardiology with a moderate strength of evidence 5, 17
For patients with CAD, either aspirin or clopidogrel as monotherapy is recommended, with consideration of patient-specific factors such as gastrointestinal bleeding history and cost concerns, as recommended by the American College of Chest Physicians with a moderate strength of evidence 6, 9
For secondary prevention after stroke or TIA, aspirin (50-100 mg daily) or clopidogrel (75 mg daily) as monotherapy is recommended, with a moderate strength of evidence supporting its use, as recommended by the European Society of Cardiology 17
For acute coronary syndromes, dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor for 12 months is recommended, with enoxaparin added in the acute setting if necessary, with a high strength of evidence supporting its use, as recommended by the European Society of Cardiology 9, 12