Can patients with heart failure and atrial fibrillation receive both clopidogrel (Plavix) and rivaroxaban (Xarelto) concurrently?

From the Guidelines

Yes, patients with heart failure and atrial fibrillation can receive both clopidogrel (Plavix) and rivaroxaban (Xarelto) concurrently, as this combination is considered a form of dual antithrombotic therapy.

Key Points

• The PIONEER AF-PCI trial showed that double therapy with rivaroxaban and a P2Y12 inhibitor (such as clopidogrel) was associated with fewer bleeding complications compared to triple therapy with a vitamin K antagonist, aspirin, and a P2Y12 inhibitor 1.
• The RE-DUAL PCI trial also demonstrated that double therapy with dabigatran and a P2Y12 inhibitor was associated with a lower risk of bleeding compared to triple therapy with warfarin, aspirin, and a P2Y12 inhibitor 1.
• A meta-analysis of these trials found that double antithrombotic therapy was associated with a halving of the odds of major and minor bleeding compared to triple therapy, without an increase in major adverse cardiovascular events 1.
• The 2020 ESC guidelines recommend the use of dual antithrombotic therapy with a non-vitamin K antagonist oral anticoagulant (such as rivaroxaban) and a P2Y12 inhibitor (such as clopidogrel) in patients with atrial fibrillation undergoing percutaneous coronary intervention 1.
• The 2020 ACC expert consensus decision pathway also recommends the use of dual antithrombotic therapy in patients with atrial fibrillation or venous thromboembolism undergoing percutaneous coronary intervention or with atherosclerotic cardiovascular disease 1.

Important Considerations

• The dose of rivaroxaban used in these trials was 15 mg once daily, which is lower than the dose recommended for stroke prophylaxis in atrial fibrillation 1.
• The choice of P2Y12 inhibitor (such as clopidogrel or ticagrelor) should be based on the individual patient's risk factors and clinical characteristics 1.
• Patients on dual antithrombotic therapy should be closely monitored for bleeding complications and adjusted as needed 1.

From the FDA Drug Label

1. 4 Anticoagulants and NSAIDs/Aspirin Coadministration of enoxaparin, warfarin, aspirin, clopidogrel and chronic NSAID use may increase the risk of bleeding [see Clinical Pharmacology (12. 3)]. Avoid concurrent use of XARELTO with other anticoagulants due to increased bleeding risk unless benefit outweighs risk. Promptly evaluate any signs or symptoms of blood loss if patients are treated concomitantly with aspirin, other platelet aggregation inhibitors, or NSAIDs [see Warnings and Precautions (5.2)] .

The use of rivaroxaban (Xarelto) and clopidogrel (Plavix) concurrently may increase the risk of bleeding.

• The FDA label advises to avoid concurrent use of XARELTO with other anticoagulants, including antiplatelet agents like clopidogrel, due to increased bleeding risk unless the benefit outweighs the risk.
• Patients with heart failure and atrial fibrillation who are considering concurrent use of rivaroxaban and clopidogrel should be closely monitored for signs and symptoms of blood loss 2.
• The decision to use these medications together should be made with caution, weighing the potential benefits against the increased risk of bleeding.

From the Research

Anticoagulation and Antiplatelet Therapy in Patients with Heart Failure and Atrial Fibrillation

• The use of anticoagulants and antiplatelet agents in patients with heart failure and atrial fibrillation is a complex issue, with multiple factors to consider, including the risk of thromboembolism and bleeding 3, 4, 5, 6, 7.
• Studies have shown that patients with atrial fibrillation and heart failure are at a high risk of thromboembolism, and anticoagulation therapy is essential to prevent stroke and systemic embolism 4, 7.
• The use of dual therapy, consisting of an anticoagulant and an antiplatelet agent, is common in patients with atrial fibrillation and coronary artery disease, but it increases the risk of bleeding 3, 5.
• Rivaroxaban, a direct oral anticoagulant, has been shown to be effective and safe in patients with atrial fibrillation and heart failure, and it may be used as an alternative to warfarin 4, 7.
• The combination of rivaroxaban and clopidogrel has been studied in patients with coronary artery disease and atrial fibrillation, and it has been shown to be effective in reducing the risk of thromboembolism and bleeding 5, 6.

Specific Considerations for Clopidogrel and Rivaroxaban

• The use of clopidogrel and rivaroxaban concurrently may be considered in patients with heart failure and atrial fibrillation, but the decision should be based on individual patient factors, including the risk of thromboembolism and bleeding 5, 6.
• Studies have shown that the combination of clopidogrel and rivaroxaban is effective in reducing the risk of thromboembolism and bleeding in patients with coronary artery disease and atrial fibrillation 5, 6.
• However, the optimal duration of dual therapy and the specific patient populations that may benefit from this combination are not well established, and further studies are needed to clarify these issues 3, 5, 6.