Can a patient take cilostazol and clopidogrel (Plavix) together?

Cilostazol and Clopidogrel Combination Therapy

Yes, patients can safely take cilostazol and clopidogrel together, and this combination may provide enhanced antiplatelet effects without significantly increasing bleeding risk compared to single antiplatelet therapy. 1

Evidence for Safety and Efficacy

The American College of Chest Physicians guidelines support the use of both medications in specific clinical scenarios:

• For patients with noncardioembolic ischemic stroke or TIA, both cilostazol (100 mg twice daily) and clopidogrel (75 mg once daily) are individually recommended as antiplatelet options 2
• For patients with peripheral arterial disease (PAD) and intermittent claudication, cilostazol can be added to standard antiplatelet therapy (which includes clopidogrel) 2

Clinical Evidence

Research has demonstrated several important points about this combination:

• A crossover trial in PAD patients showed that adding cilostazol to clopidogrel did not further prolong bleeding time beyond what was observed with clopidogrel alone 1
• The CSPS.com trial found that the combination of cilostazol and clopidogrel significantly reduced ischemic stroke recurrence (HR 0.447) without increasing bleeding risk in high-risk, noncardioembolic stroke patients 3
• Cilostazol-based dual antiplatelet therapy has been shown to reduce clopidogrel resistance and suppress new ischemic lesions without increasing hemorrhagic complications in patients undergoing carotid artery stenting 4

Mechanism of Action and Complementary Effects

The safety of combining these medications is likely due to their different mechanisms of action:

• Clopidogrel inhibits platelet aggregation by blocking the P2Y12 ADP receptor
• Cilostazol works as a phosphodiesterase-3 inhibitor, increasing intracellular cAMP levels 5

Monitoring and Precautions

While the combination is generally safe, certain precautions should be observed:

1. Monitor for bleeding signs and symptoms as recommended for all antiplatelet therapies 2
2. Avoid in patients with heart failure as cilostazol is contraindicated in heart failure due to potential for tachyarrhythmias 2, 5
3. Use caution in elderly patients (≥75 years) who may have higher risk of bleeding with antiplatelet therapies 2
4. Consider renal function as cilostazol should be used with caution in patients with severe renal impairment 5

Common Side Effects to Monitor

• Headache (most common with cilostazol)
• Diarrhea and other GI effects
• Palpitations
• Dizziness

Clinical Applications

This combination may be particularly beneficial in:

• Patients with high-risk noncardioembolic stroke 3
• Patients with PAD and intermittent claudication 2
• Patients with clopidogrel resistance 6

Interestingly, research suggests that cilostazol may actually decrease gastric bleeding and damage induced by aspirin, unlike other antiplatelet agents that tend to increase these risks 7. This protective effect may provide an additional benefit when using cilostazol in combination antiplatelet regimens.

In conclusion, the cilostazol-clopidogrel combination appears to be safe and may offer enhanced antiplatelet effects in appropriate clinical scenarios, particularly for patients with cerebrovascular disease or PAD.