What is the best antiplatelet therapy, single or dual, for a patient with congestive heart failure (CHF) and reduced ejection fraction, considering options such as aspirin, clopidogrel, and ticagrelor?

Antiplatelet Therapy for Heart Failure with Reduced Ejection Fraction

For patients with heart failure and reduced ejection fraction (HFrEF) without other indications for dual antiplatelet therapy, single antiplatelet therapy is recommended over dual antiplatelet therapy. 1

Recommendations for Antiplatelet Therapy in HFrEF

Single Antiplatelet Therapy

• For patients with HFrEF in sinus rhythm without recent acute coronary syndrome or coronary intervention, single antiplatelet therapy is the preferred approach 1
• Aspirin 75-100 mg daily is recommended as first-line antiplatelet therapy for patients with HFrEF who have established coronary artery disease 1
• Clopidogrel 75 mg daily is an appropriate alternative for patients who cannot tolerate aspirin 1

Special Considerations for Anticoagulation

• For patients with HFrEF and severe left ventricular dysfunction (ejection fraction ≤35%) without evidence of left atrial or ventricular thrombus, the benefit of anticoagulation versus antiplatelet therapy is uncertain and should be based on individual risk factors 1
• In patients with HFrEF who have left ventricular thrombus, anticoagulant therapy is recommended for at least three months 1
• For patients with anterior MI and high risk for LV thrombus (EF <40%, anteroapical wall motion abnormality), warfarin (INR 2.0-3.0) plus low-dose aspirin is recommended for the first 3 months 1

Evidence Against Dual Antiplatelet Therapy

• In the WATCH trial, comparing aspirin, clopidogrel, and warfarin in patients with HFrEF, there was no difference in the primary composite outcome between treatment groups, but warfarin was associated with higher bleeding risk 1
• The American College of Chest Physicians guidelines specifically suggest single over dual antiplatelet therapy with aspirin plus clopidogrel for patients with established coronary artery disease 1

Evidence for Specific Antiplatelet Agents

Aspirin

• Aspirin 75-100 mg daily remains the first-line antiplatelet therapy for patients with previous MI or revascularization 1
• Low-dose aspirin has established efficacy in reducing cardiovascular events in patients with established coronary artery disease 1

Clopidogrel

• Clopidogrel 75 mg daily is recommended as an alternative to aspirin in patients with aspirin intolerance 1
• The CAPRIE trial showed improved efficacy of clopidogrel compared to aspirin for prevention of major adverse cardiovascular events with similar bleeding rates 1, 2

Ticagrelor

• Ticagrelor is not recommended as part of triple antithrombotic therapy with aspirin and an oral anticoagulant 1
• Ticagrelor has similar efficacy to clopidogrel but with higher rates of adverse events in some studies 1, 3

Clinical Considerations and Caveats

• Patients with recent coronary interventions (within 6-12 months) may require dual antiplatelet therapy regardless of HFrEF status 1
• The PLUTO-CHF trial showed that combination of clopidogrel and aspirin provided significantly greater inhibition of platelet activity than aspirin alone in patients with HFrEF, but this has not translated to improved clinical outcomes in larger trials 4
• The WARCEF trial showed that warfarin reduced the risk of ischemic stroke compared to aspirin in patients with HFrEF, but this benefit was offset by increased bleeding risk 1
• For patients with HFrEF who also have atrial fibrillation, anticoagulation is generally preferred over antiplatelet therapy 1

Conclusion

For most patients with HFrEF without other indications for dual therapy, single antiplatelet therapy (preferably aspirin or clopidogrel if aspirin-intolerant) is the recommended approach based on current evidence and guidelines 1.