Can Plavix (clopidogrel) be used with Eliquis (apixaban) together?

Can Plavix and Eliquis Be Used Together?

Yes, Plavix (clopidogrel) and Eliquis (apixaban) can be used together in specific clinical situations—primarily in patients with atrial fibrillation who undergo percutaneous coronary intervention (PCI) with stenting—but this combination significantly increases bleeding risk and requires careful patient selection, risk stratification, shortest possible duration, and mandatory proton pump inhibitor (PPI) prophylaxis. 1

Clinical Scenarios Where Combination May Be Appropriate

Atrial Fibrillation with PCI/Stenting

• Dual therapy (apixaban + clopidogrel) is preferred over triple therapy (apixaban + aspirin + clopidogrel) in most patients with atrial fibrillation requiring anticoagulation who undergo PCI with stenting 1
• This approach minimizes bleeding risk while maintaining adequate antithrombotic protection 1
• The European Society of Cardiology specifically recommends this combination for AF patients post-PCI due to the increased bleeding risk inherent in triple therapy 1

Duration Considerations

• Use the shortest appropriate duration of dual therapy based on stent type and bleeding risk 1
• Plan for de-escalation to anticoagulation monotherapy as soon as clinically feasible 1

Critical Bleeding Risk Data

Evidence from Clinical Trials

• The APPRAISE-2 trial was terminated early due to unacceptably high bleeding rates when apixaban was added to antiplatelet therapy in acute coronary syndrome patients 2, 3, 4
• Major bleeding rates with apixaban plus single antiplatelet therapy: 2.8% per year vs. 0.6% per year with placebo 2
• Major bleeding rates with apixaban plus dual antiplatelet therapy (aspirin + clopidogrel): 5.9% per year vs. 2.5% per year with placebo 2, 4
• In ARISTOTLE, concomitant aspirin use increased bleeding risk on apixaban from 1.8% to 3.4% per year 2

FDA Warning

• The FDA label explicitly states: "Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding" 2
• Limited data (only 2.3%) exists on dual antiplatelet therapy with apixaban from major trials 2

Mandatory Risk Stratification Before Combining

High-Risk Patients (Avoid Combination)

• Advanced age >75 years 1, 5
• History of gastrointestinal bleeding 1, 5
• Renal dysfunction (CrCl <30 mL/min) 5
• Hepatic impairment 5
• Uncontrolled hypertension 5
• Concurrent use of NSAIDs or corticosteroids 1, 5

Moderate Risk (Use with Extreme Caution)

• Age 65-75 years 5
• Mild-moderate renal impairment 5
• Stable cardiovascular disease 5

Required Management Protocol

Step 1: Confirm Dual Indication

• Verify that both anticoagulation (for AF, VTE, etc.) and antiplatelet therapy (for recent PCI/stenting) are absolutely necessary 1
• Consider whether anticoagulation alone might suffice once the high-risk stent period has passed 6

Step 2: Assess Bleeding Risk

• Use validated bleeding risk scores 1
• Document all high-risk features listed above 1, 5

Step 3: Mandatory GI Protection

• Initiate proton pump inhibitor (PPI) prophylaxis in all patients receiving this combination 1
• PPIs reduce upper GI bleeding risk more effectively than H2 receptor antagonists 1
• This is particularly critical given the 3-6 fold increase in GI bleeding risk with combined anticoagulant-antiplatelet therapy 5

Step 4: Plan De-escalation Timeline

• Establish a specific date to discontinue clopidogrel and continue apixaban monotherapy 1
• Typical duration: 1-6 months depending on stent type (drug-eluting vs. bare metal) and bleeding risk 1

Step 5: Close Monitoring

• Complete blood count at baseline and regularly 5
• Renal function tests (apixaban is partially renally eliminated) 5
• Blood pressure monitoring 5
• Stool occult blood testing 5
• Patient education on bleeding warning signs (melena, hematochezia, hematemesis, severe headache, unexplained bruising) 5

Alternative Considerations

When Anticoagulation Alone May Suffice

• In patients with atrial fibrillation and stable coronary disease (not requiring recent PCI), anticoagulation alone may be as effective as antiplatelet therapy for long-term management 6
• The combination of aspirin and clopidogrel is inferior to oral anticoagulants for stroke prevention in AF patients 7

Contraindicated Scenario

• Do not use this combination in patients unable to take warfarin due to bleeding risk, as clopidogrel plus aspirin carries similar bleeding risk to warfarin 7
• In acute coronary syndrome patients without a clear indication for anticoagulation, this combination showed no efficacy benefit but increased bleeding 4

Common Pitfalls to Avoid

• Failing to prescribe PPI prophylaxis—this is mandatory, not optional 1
• Continuing combination therapy indefinitely—always establish a de-escalation plan 1
• Using triple therapy (apixaban + aspirin + clopidogrel) when dual therapy suffices 1
• Ignoring age >75 years as a contraindication 1, 5
• Not monitoring renal function, which affects apixaban clearance 5
• Adding NSAIDs or other anticoagulants without recognizing the compounded bleeding risk 1, 5, 2