What are the interactions between Clopidogrel (Plavix) and Apixaban (Eliquis)?

From the Guidelines

Clopidogrel should not be used together with Eliquis (apixaban) unless absolutely necessary and under close medical supervision, as this combination significantly increases the risk of bleeding complications, as evident from recent studies 1. When considering the use of clopidogrel with Eliquis, it's crucial to weigh the benefits against the potential risks, particularly the increased risk of bleeding. Both medications affect blood clotting through different mechanisms - clopidogrel is an antiplatelet drug that prevents platelets from sticking together, while Eliquis is an anticoagulant that inhibits clotting factor Xa. Using these medications together creates a dangerous "double effect" on blood clotting that can lead to serious or life-threatening bleeding complications. Some key points to consider when making this decision include:

• The dose of aspirin should not exceed 100 mg when used with anticoagulation therapy 1
• The addition of clopidogrel to aspirin and warfarin can be considered in certain high-risk patients, but the risk of bleeding needs to be carefully weighed against the potential benefits, and should not exceed 6 months 1
• For patients with AF or an indication for anticoagulation, acute coronary syndrome (ACS) is the most common scenario when dual antiplatelet therapy must be initiated on top of anticoagulation, and in these cases, the initial antiplatelet of choice is clopidogrel due to the higher risk of bleeding associated with ticagrelor versus clopidogrel 1
• A proton pump inhibitor should be initiated prophylactically in patients on simultaneous antiplatelet and anticoagulant therapy to reduce the risk of GI bleeding 1 In rare situations where a patient has both atrial fibrillation and recent coronary stent placement, a physician might temporarily prescribe both medications with careful monitoring, but this is generally avoided whenever possible. If you're currently taking both medications or considering this combination, consult your doctor immediately to discuss safer alternatives and to determine the best course of treatment based on your individual needs and medical history.

From the FDA Drug Label

7 DRUG INTERACTIONS Apixaban is a substrate of both CYP3A4 and P-gp. Inhibitors of CYP3A4 and P-gp increase exposure to apixaban and increase the risk of bleeding.

1. 3 Anticoagulants and Antiplatelet Agents Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding

The use of clopidogrel (often referred to in the context of being "cloistered with") with apixaban (Eliquis) may increase the risk of bleeding.

• In the APPRAISE-2 trial, the rate of ISTH major bleeding was higher with apixaban compared to placebo in patients receiving single antiplatelet therapy (2.8% per year with apixaban versus 0.6% per year with placebo) and dual antiplatelet therapy (5.9% per year with apixaban versus 2.5% per year with placebo) 2.
• Concomitant use of aspirin and apixaban increased the bleeding risk in the ARISTOTLE trial 2. It is essential to carefully weigh the benefits and risks of using apixaban with antiplatelet agents, including clopidogrel.

From the Research

Using Cloistered with Eliquis

There are no direct studies on the use of "cloistered" with Eliquis. However, we can look at the studies on the combination of antiplatelet and antithrombotic therapy, which may provide some insights.

Combination Therapy

• The study 3 discusses the combination of aspirin and clopidogrel, which has a stronger antiplatelet effect and provides superior antithrombotic protection.
• Another study 4 talks about the risks and benefits of combining antiplatelet and antithrombotic therapy, including the use of newer antithrombotic medications like rivaroxaban, dabigatran, and apixaban.
• The study 5 found that combination therapy with aspirin, clopidogrel, and warfarin following coronary stenting is associated with a significant risk of bleeding.

Eliquis (Apixaban) and Antiplatelet Therapy

• The study 6 evaluates the potential benefit of apixaban plus aspirin compared with standard dual antiplatelet therapy in reducing thrombotic restenosis and artery re-occlusion in patients undergoing endovascular infrapopliteal revascularization.
• Another study 7 compares apixaban with dual-antiplatelet therapy (clopidogrel and aspirin) in high-risk patients with acute non-disabling cerebrovascular events.

Key Findings

• Combination therapy with antiplatelet and antithrombotic agents can provide superior protection against adverse vascular events, but it also increases the risk of bleeding.
• Apixaban, a newer antithrombotic medication, has been shown to be effective and safe in various clinical trials, and its use with aspirin may be a viable alternative to dual antiplatelet therapy in certain patient populations.