What are the indications for Aspirin (ASA) and Warfarin?

Indications for Aspirin and Warfarin

Aspirin (75-162 mg daily) is the first-line antiplatelet agent for all patients with coronary artery disease, peripheral arterial disease, and cerebrovascular disease unless contraindicated, while warfarin (INR 2.0-3.0) is reserved for specific high-risk conditions including atrial fibrillation, mechanical heart valves, left ventricular thrombus, and venous thromboembolism. 1

Aspirin Indications

Cardiovascular Disease

• All patients with coronary artery disease should receive aspirin 75-162 mg daily indefinitely unless contraindicated 1
• Acute coronary syndromes (ACS): Initial dose 162-325 mg immediately when ACS is suspected or diagnosed, followed by maintenance dose 75-162 mg daily 1
• Post-myocardial infarction: Continue aspirin indefinitely for secondary prevention 1
• Post-coronary artery bypass grafting: Start aspirin within 6 hours after surgery at 100-325 mg daily for at least 1 year to reduce saphenous vein graft closure 1
• Post-PCI with stenting: Use 81 mg daily maintenance dose (preferred over higher doses to reduce bleeding risk) in combination with a P2Y12 inhibitor 1

Cerebrovascular Disease

• Extracranial carotid or vertebral atherosclerosis with prior ischemic stroke or TIA: aspirin 75-325 mg daily 1
• Secondary stroke prevention: Aspirin 75-325 mg daily is equally effective as warfarin for noncardioembolic ischemic stroke 2

Peripheral Arterial Disease

• Symptomatic atherosclerotic peripheral artery disease of the lower extremity: aspirin 75-325 mg daily or clopidogrel 75 mg daily 1
• Asymptomatic peripheral artery disease: Benefits are not well established 1

Warfarin Indications

Cardiac Conditions

• Atrial fibrillation with high-risk features: Warfarin (INR 2.0-3.0) for any high-risk factor including prior stroke/TIA, age ≥75 years, hypertension, diabetes, heart failure, or left ventricular dysfunction 1
• Mechanical heart valve prostheses: Warfarin is mandatory (INR target depends on valve type and position) 1, 3
• Left ventricular thrombus: Warfarin (INR 2.0-3.0) 1

Venous Thromboembolism

• Deep vein thrombosis or pulmonary embolism: Warfarin (INR 2.0-3.0) for at least 3 months for provoked events, 6 months for unprovoked proximal DVT, and indefinite therapy for recurrent idiopathic thrombosis or thrombophilia 1
• Prevention after major orthopedic or gynecologic surgery: Warfarin (INR 2.0-3.0) 1

Cerebrovascular Disease

• Cardioembolic stroke prevention: Warfarin is superior to aspirin for preventing cardiogenic embolism 2
• Systemic embolism with patent foramen ovale or cryptogenic stroke: Warfarin may be considered, though evidence is limited 1

Combination Therapy: Aspirin Plus Warfarin

When Combination is Indicated

The combination of aspirin and warfarin should only be used when there is a compelling indication for anticoagulation PLUS a separate indication for antiplatelet therapy. 1

• Mechanical heart valve with coronary artery disease: Low-dose aspirin (75-81 mg daily) plus warfarin (INR 2.0-3.0) 1
• Atrial fibrillation with acute coronary syndrome or recent PCI: Aspirin 75-81 mg daily plus warfarin (INR 2.0-2.5 when combined with clopidogrel; INR 2.0-3.0 when combined with aspirin alone) 1
• Left ventricular thrombus with coronary artery disease: Aspirin 75-81 mg daily plus warfarin 1
• Post-MI with compelling anticoagulation indication: Combination therapy may be considered, though warfarin alone (INR 2.8) or combination therapy (INR 2.2) both reduce events compared to aspirin alone 4

When Combination is NOT Indicated

Antiplatelet therapy is recommended in preference to anticoagulant therapy for treating atherosclerosis alone. 1

• Stable coronary artery disease without other indications: Combination therapy increases bleeding without clear benefit 1
• Atrial fibrillation or venous thromboembolism without recent ACS/PCI: Adding aspirin to warfarin increases bleeding (26.0% vs 20.3% at 1 year) and major bleeding (5.7% vs 3.3%) without reducing thrombosis 5
• Post-MI beyond 12 months without mechanical valve or atrial fibrillation: Low-intensity warfarin plus aspirin showed no benefit over aspirin alone in CARS and CHAMP trials 1

Critical Dosing Considerations

Aspirin Dosing

• Maintenance dose 75-162 mg daily is preferred over higher doses due to dose-dependent bleeding risk (major bleeding: 2.0% with <100 mg, 2.3% with 100-200 mg, 4.0% with >200 mg) without additional efficacy 1
• Initial ACS dose: 162-325 mg non-enteric coated for rapid buccal absorption 1

Warfarin Dosing

• Standard intensity (INR 2.0-3.0) for most indications including atrial fibrillation, venous thromboembolism, and when combined with aspirin 1
• Lower target (INR 2.0-2.5) when warfarin is combined with aspirin AND clopidogrel (triple therapy) 1
• High-intensity warfarin (INR 3.0-4.5) is dangerous in cerebral ischemia of arterial origin and should be avoided 1

Common Pitfalls

• Avoid combining warfarin and aspirin without a specific indication: This practice is common (37.5% in one registry) but increases bleeding without reducing thrombosis in patients with atrial fibrillation or venous thromboembolism alone 5
• Monitor closely when triple therapy is necessary: The combination of warfarin, aspirin, and clopidogrel significantly increases bleeding risk and requires close monitoring 1
• Do not use low fixed-dose warfarin (1-3 mg) with aspirin: This approach showed no benefit over aspirin alone in post-MI patients 1
• Warfarin is contraindicated in pregnancy, particularly first trimester, though may be necessary in second/third trimesters for mechanical valves 3