Can you take cilostazol and Eliquis (apixaban) together?

Concurrent Use of Cilostazol and Apixaban (Eliquis)

Yes, cilostazol and apixaban (Eliquis) can generally be used together, but this combination requires careful monitoring for bleeding risk due to their combined antithrombotic effects.

Mechanism and Safety Considerations

• Cilostazol is a phosphodiesterase-3 inhibitor with antiplatelet, vasodilating, and antiproliferative effects primarily used for peripheral arterial disease (PAD) and claudication symptoms 1
• Apixaban (Eliquis) is a direct oral anticoagulant (DOAC) that inhibits factor Xa in the coagulation cascade
• These medications work through different mechanisms:
  • Cilostazol inhibits platelet aggregation through increased cAMP levels
  • Apixaban directly inhibits clotting factor Xa

Evidence Supporting Combination Use

• While the American College of Cardiology/American Heart Association guidelines don't specifically address this combination, they do provide relevant guidance:

  • Cilostazol is recommended as effective therapy for claudication symptoms in PAD (Class I, Level A evidence) 2
  • Anticoagulation (like apixaban) should not be used to reduce cardiovascular events in PAD patients (Class III: Harm, Level A) 2
  • However, this recommendation is specifically about using anticoagulation for PAD itself, not when anticoagulation is indicated for other conditions

• Limited evidence suggests combination therapy with anticoagulants and cilostazol may be safe:

  • A case report demonstrated successful long-term use (32 months) of rivaroxaban (another factor Xa inhibitor similar to apixaban) with cilostazol in a frail elderly patient with critical limb ischemia and atrial fibrillation without major bleeding events 3

Important Precautions

• Monitor closely for signs of bleeding, as both medications affect hemostasis through different mechanisms
• Cilostazol is contraindicated in patients with heart failure due to potential for tachyarrhythmias 4
• Cilostazol is metabolized by CYP3A4 and CYP2C19 enzymes, but apixaban interactions through this pathway are minimal 1
• Reduced dosing of cilostazol may be considered when used with other antithrombotic agents in high-risk patients

Clinical Recommendations

1. Ensure both medications are independently indicated:

   • Apixaban for appropriate indications (atrial fibrillation, VTE, etc.)
   • Cilostazol for claudication symptoms in PAD

2. Assess bleeding risk factors:

   • Age >75 years
   • History of GI bleeding
   • Renal impairment
   • Concomitant use of other antiplatelets (aspirin, clopidogrel)
   • Low body weight (<60 kg)

3. Consider alternative to cilostazol if:

   • Patient has heart failure (absolute contraindication)
   • Extremely high bleeding risk
   • Severe renal impairment

4. Monitoring recommendations:

   • Regular assessment for bleeding signs (bruising, melena, hematuria)
   • CBC to monitor for anemia
   • Renal function tests

Special Considerations

• If patient is also on aspirin or clopidogrel (triple therapy), bleeding risk increases substantially
• The CSPS.com trial showed that dual antiplatelet therapy using cilostazol with either aspirin or clopidogrel reduced stroke recurrence without significantly increasing bleeding risk 5, suggesting cilostazol may have a more favorable bleeding profile than other antiplatelets
• For patients with PAD and intermittent claudication who also require anticoagulation, the benefits of symptom improvement with cilostazol may outweigh the theoretical increased bleeding risk when appropriate monitoring is in place

Remember that while this combination can be used, the patient should be informed about potential increased bleeding risk and educated about signs of bleeding to report immediately.