Cilostazol Use in PAD Patients Already on Antiplatelet Therapy
Yes, cilostazol should be added to aspirin or clopidogrel in PAD patients with persistent claudication symptoms despite exercise therapy and smoking cessation. 1, 2
Evidence-Based Recommendation
The American College of Chest Physicians explicitly recommends adding cilostazol 100 mg twice daily to baseline single antiplatelet therapy (aspirin 75-100 mg daily OR clopidogrel 75 mg daily) when claudication remains refractory to exercise therapy and smoking cessation (Grade 2C). 1, 2 This represents the standard approach: single antiplatelet therapy remains the foundation for cardiovascular event prevention, while cilostazol is added specifically for symptom management. 1
Mechanism and Clinical Benefit
Cilostazol functions as a phosphodiesterase III inhibitor, providing vasodilation and platelet inhibition through a different mechanism than aspirin or clopidogrel. 3 The drug improves maximal walking distance by 40-60% after 12-24 weeks of therapy and enhances quality of life beyond just walking distance improvements. 2, 3, 4 Importantly, the 2024 ACC/AHA guidelines confirm that cilostazol is effective medical therapy for leg symptoms and walking impairment due to claudication. 1
Safety Profile with Combination Therapy
A critical safety study demonstrated that cilostazol does NOT prolong bleeding time when used alone, unlike aspirin or clopidogrel. 5 In a crossover trial of 21 PAD patients, aspirin alone or clopidogrel alone significantly increased bleeding times, but cilostazol alone did not. 5 When cilostazol was added to aspirin/clopidogrel regimens, no further bleeding time prolongation occurred beyond what was observed with aspirin and clopidogrel together. 5 This evidence directly supports the safety of combining cilostazol with standard antiplatelet therapy.
Treatment Algorithm
Step 1: Establish baseline antiplatelet therapy
- Clopidogrel 75 mg daily (preferred) OR aspirin 75-325 mg daily for cardiovascular event prevention 1, 2
Step 2: Implement non-pharmacologic interventions
- Structured exercise program 1
- Smoking cessation 1
- Statin therapy (all PAD patients) 1
- Antihypertensive therapy if indicated 1
Step 3: Add cilostazol if symptoms persist
- Cilostazol 100 mg twice daily added to existing antiplatelet therapy 1, 2, 3
- Continue indefinitely if tolerated and effective 3
Critical Contraindication
Cilostazol is absolutely contraindicated in patients with heart failure of ANY severity. 3 As a phosphodiesterase III inhibitor, cilostazol increases mortality risk in heart failure patients. 3 This is the single most important safety consideration that must be verified before prescribing.
Common Side Effects and Discontinuation
Headache, diarrhea, dizziness, and palpitations are common side effects. 1 In one trial, 20% of patients discontinued cilostazol within 3 months due to adverse effects. 1 However, these side effects do not represent safety concerns regarding bleeding or cardiovascular events when combined with antiplatelet therapy.
Post-Revascularization Considerations
After lower extremity revascularization, continue long-term single antiplatelet therapy (aspirin 75-100 mg daily OR clopidogrel 75 mg daily). 1, 2 Cilostazol may be added for its anti-restenotic properties, as it decreases restenosis rates after endovascular interventions. 3
What NOT to Do
- Do NOT use cilostazol as monotherapy—patients still require aspirin or clopidogrel for cardiovascular mortality reduction, as cilostazol does not reduce cardiovascular events. 2
- Do NOT prescribe cilostazol to any patient with current or historical heart failure. 3
- Do NOT use dual antiplatelet therapy (aspirin + clopidogrel) routinely for claudication, as this increases bleeding without improving walking distance. 3