Safety of Using Cilostazol with Clopidogrel (Plavix)
The combination of cilostazol with clopidogrel (Plavix) is generally safe and may provide additional benefits in specific patient populations without significantly increasing bleeding risk.
Safety Profile of the Combination
- Triple antiplatelet therapy using cilostazol in addition to clopidogrel does not significantly increase bleeding risk compared to dual antiplatelet therapy with aspirin and clopidogrel 1.
- When cilostazol was added to clopidogrel-based regimens, no significant differences in major or minor bleeding events were observed compared to clopidogrel alone 2, 3.
- Unlike the combination of aspirin and clopidogrel which significantly increases bleeding times, adding cilostazol to clopidogrel does not further prolong bleeding time 4.
Clinical Benefits of the Combination
- The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing bleeding risk in patients with noncardioembolic, high-risk stroke 2.
- In patients with Type 2 diabetes and symptomatic lower extremity arterial disease, adding cilostazol to clopidogrel significantly reduced composite ischemic events (stroke/TIA, MI, vascular death) compared to clopidogrel monotherapy (HR 0.468; 95% CI, 0.252-0.870) 3.
- The combination improved ankle-brachial index and pain-free walking distance in patients with peripheral arterial disease 3.
Mechanism of Action and Pharmacology
- Cilostazol has a different mechanism of action than clopidogrel, which may explain the complementary effects without additive bleeding risk 1.
- Cilostazol is a phosphodiesterase inhibitor with vasodilatory and antiplatelet properties, while clopidogrel is a P2Y12 receptor antagonist 1.
- Cilostazol is metabolized by CYP450 enzymes and has a half-life of approximately 11 hours 1.
Special Considerations and Contraindications
- Cilostazol is contraindicated in patients with heart failure due to potential risk of ventricular tachyarrhythmias 1.
- Caution should be exercised in patients with left ventricular outflow tract obstruction 1.
- Monitoring of platelets and white blood cell counts is recommended when using cilostazol 1.
Specific Patient Populations
- In patients undergoing percutaneous coronary intervention (PCI), triple antiplatelet therapy with cilostazol, aspirin, and clopidogrel reduced long-term cardiac and cerebral events compared to dual therapy, especially in high-risk patients 5.
- The combination of clopidogrel and low-dose cilostazol (100 mg) was effective in reducing clopidogrel resistance, suggesting that even lower doses of cilostazol may provide benefits when combined with clopidogrel 6.
Guideline Recommendations
- For patients with peripheral arterial disease and intermittent claudication refractory to exercise therapy, guidelines suggest the use of cilostazol in addition to standard antiplatelet therapy (aspirin 75-100 mg daily or clopidogrel 75 mg daily) 1.
- For patients undergoing elective BMS or DES stent placement, guidelines recommend low-dose aspirin and clopidogrel alone rather than adding cilostazol, but suggest cilostazol as a substitute for either aspirin or clopidogrel in patients with allergies or intolerances to these drugs 1.
Common Pitfalls and Caveats
- Cilostazol can cause tachyarrhythmia and hypotension, and may exacerbate angina pectoris or myocardial infarction in patients with ischemic heart disease 1.
- Patients should be monitored for headache, which occurs in up to 25% of patients within the first two weeks of starting cilostazol 1.
- Drug interactions should be considered as cilostazol is metabolized by CYP450 enzymes 1.
In conclusion, the combination of cilostazol with clopidogrel appears to be safe without significantly increasing bleeding risk, and may provide additional benefits in specific patient populations such as those with peripheral arterial disease, diabetes, or high risk for ischemic stroke.