Is aspirin (acetylsalicylic acid) contraindicated with warfarin (anticoagulant)?

Aspirin is Generally Contraindicated with Warfarin Due to Increased Bleeding Risk

The combination of aspirin and warfarin is generally contraindicated due to significantly increased bleeding risk without additional thrombotic protection in most clinical scenarios. 1, 2

Bleeding Risk of Combined Therapy

The combination of warfarin and aspirin substantially increases bleeding risk:

• Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, potentiate the risk of bleeding with warfarin 1
• The FDA label for warfarin specifically warns about increased bleeding risk when administered with NSAIDs, including aspirin 2
• In the SPORTIF study, AF patients with prior stroke or TIA who received aspirin plus warfarin had significantly higher rates of major bleeding (4.95% per year) compared to warfarin alone (1.5% per year) 1
• A recent study found that patients receiving combination therapy had higher rates of major bleeding (14.9%) compared to warfarin monotherapy (7.9%) 3

Clinical Scenarios Where Combination May Be Considered

While generally contraindicated, there are specific limited clinical scenarios where combination therapy may be considered:

1. Mechanical Heart Valves:

   • Patients with mechanical heart valves may benefit from lifelong low-dose aspirin (75-100mg/day) in addition to warfarin 1
   • The combination reduced mortality and major systemic embolism in high-risk patients with mechanical valve prostheses 4

2. Post-Valve Implantation:

   • After bioprosthetic aortic valve implantation, adding aspirin to warfarin may be reasonable for the initial 3 months in patients at high risk for thrombotic complications 1
   • However, aspirin dose should not exceed 100 mg and a proton pump inhibitor should be considered 1

3. Acute Coronary Syndrome with AF:

   • Triple therapy (aspirin + P2Y12 inhibitor + anticoagulant) should be limited to 30 days maximum 1, 5
   • After this period, discontinue aspirin and continue P2Y12 inhibitor (preferably clopidogrel) with anticoagulation 5

Recommendations for Clinical Practice

1. For Atrial Fibrillation:

   • Use warfarin alone (target INR 2.0-3.0) without aspirin 1
   • There is no evidence that combining anticoagulation with an antiplatelet agent reduces stroke risk compared to anticoagulant therapy alone 1

2. For Patients with Vascular Disease:

   • Despite common practice, the addition of aspirin to warfarin for patients with stable vascular disease is generally inappropriate 6
   • Studies show that 20% of patients taking warfarin use concomitant aspirin inappropriately 7

3. For Patients Already on Combination Therapy:

   • Assess the indication for combination therapy
   • If no clear indication exists (mechanical heart valve, recent ACS or stent), consider discontinuing aspirin
   • Monitor INR closely when making changes to therapy

Monitoring and Risk Mitigation

If combination therapy is absolutely necessary:

• Target lower INR range when possible
• Use the lowest effective dose of aspirin (≤100 mg)
• Consider adding a proton pump inhibitor to reduce GI bleeding risk 1
• Monitor for bleeding signs more frequently
• Educate patients about bleeding symptoms requiring immediate medical attention

Conclusion

The combination of warfarin and aspirin significantly increases bleeding risk without providing additional protection against thrombotic events in most patients. This combination should be avoided unless there is a specific indication such as mechanical heart valves or recent acute coronary syndrome, and even then, the duration of combination therapy should be minimized.