Is dual antiplatelet therapy (DAPT) and Eliquis (apixaban) commonly prescribed together?

Is Dual Antiplatelet Therapy and Eliquis Commonly Prescribed Together?

Yes, dual antiplatelet therapy (DAPT) and apixaban (Eliquis) are commonly prescribed together, but only in specific clinical scenarios and for limited durations—primarily in patients with atrial fibrillation who undergo percutaneous coronary intervention (PCI) or experience acute coronary syndrome (ACS). This combination, known as "triple therapy," is associated with significantly increased bleeding risk and should be minimized in both intensity and duration 1.

Clinical Scenarios Where This Combination Occurs

The most common indication for combining DAPT with apixaban is in patients with atrial fibrillation who require coronary intervention:

• Atrial fibrillation patients undergoing PCI or experiencing ACS represent the primary population requiring this combination, as they need oral anticoagulation for stroke prevention and antiplatelet therapy for coronary thrombosis prevention 1, 2.
• Approximately 10% of patients with atrial fibrillation will experience an ACS or undergo PCI, making this a frequently encountered clinical scenario 3.
• Up to 10% of the >3 million Americans with atrial fibrillation will face this situation, highlighting how common this therapeutic challenge is in practice 3.

Current Guideline-Recommended Approach

The 2024 ESC guidelines provide clear direction on minimizing this combination:

• Triple therapy (apixaban + aspirin + P2Y12 inhibitor) should be limited to 7 days or less after PCI or ACS, followed by transition to dual therapy 1, 2.
• Dual therapy (apixaban + clopidogrel only) should continue for 6-12 months, with aspirin discontinued after the initial brief period 1, 2.
• Clopidogrel is the preferred P2Y12 inhibitor when combined with apixaban, not ticagrelor or prasugrel, due to lower bleeding risk 1, 2.

Dosing Considerations for Apixaban

When apixaban is combined with antiplatelet agents, dose selection is critical:

• Use the lowest approved dose effective for stroke prevention tested in atrial fibrillation trials when combining with antiplatelet therapy 1.
• Standard dosing is apixaban 5 mg twice daily, or 2.5 mg twice daily if the patient meets dose-reduction criteria (age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL—at least two of three criteria) 1.

Bleeding Risk Evidence

The combination carries substantial bleeding risk that must be acknowledged:

• The APPRAISE-2 trial was terminated early due to excessive bleeding when apixaban was added to antiplatelet therapy in post-ACS patients 4.
• Major bleeding rates were 2.8% per year with apixaban versus 0.6% per year with placebo in patients on single antiplatelet therapy 4.
• Bleeding rates increased to 5.9% per year with apixaban versus 2.5% per year with placebo in those on dual antiplatelet therapy 4.
• In the ARISTOTLE trial, concomitant aspirin use increased bleeding risk from 1.8% to 3.4% per year with apixaban 4.

Strategies to Minimize Bleeding Risk

When this combination is necessary, implement these protective measures:

• Prescribe a proton pump inhibitor (PPI) in all patients receiving combined anticoagulant and antiplatelet therapy to reduce gastrointestinal bleeding 1, 5.
• Limit aspirin dose to 75-100 mg daily (not higher doses) when used in combination 1.
• Use radial over femoral arterial access if PCI is performed to reduce access-site bleeding 1, 5, 6.
• Avoid ticagrelor and prasugrel as part of triple therapy; use clopidogrel exclusively 1.

What Is NOT Recommended

The guidelines are explicit about inappropriate uses:

• Adding antiplatelet therapy to anticoagulation is not recommended for stroke prevention in atrial fibrillation patients without acute coronary disease 1.
• Antiplatelet drugs are not an alternative to oral anticoagulation and should not be used for stroke prevention in atrial fibrillation 1.
• Combining OAC with antiplatelet agents without adequate indication occurs frequently but leads to more bleeding events with no clear benefit in stroke or death prevention 1.
• Triple therapy beyond 7 days should be avoided unless the patient is at exceptionally high risk for stent thrombosis 1, 2.

Common Clinical Pitfalls

Avoid these frequent errors in practice:

• Continuing triple therapy beyond the recommended brief duration (7 days) exposes patients to unnecessary bleeding risk 1, 2.
• Using ticagrelor or prasugrel instead of clopidogrel as part of triple therapy significantly increases bleeding without proven benefit 1.
• Failing to prescribe a PPI when combining these agents misses a simple intervention that reduces gastrointestinal bleeding 1, 5.
• Combining antiplatelet agents with anticoagulation in stable patients without an acute coronary indication provides no benefit and causes harm 1.

Long-Term Management

After the initial high-risk period:

• Discontinue all antiplatelet agents at 12 months and continue apixaban monotherapy for atrial fibrillation stroke prevention 1.
• Anticoagulation alone is superior to aspirin post-ACS in patients with atrial fibrillation, supporting discontinuation of antiplatelet therapy 1.
• There is no evidence to support continued antiplatelet use beyond 6-12 months unless the patient has another specific indication 1.