Is cilostazol (Pletal) appropriate for a patient with peripheral artery disease (PAD) and a history of heart failure with reduced ejection fraction?

Cilostazol is Contraindicated in Patients with Heart Failure

Cilostazol is absolutely contraindicated in this patient due to his history of heart failure with reduced ejection fraction, as stated in current guidelines and FDA labeling.

Rationale for Contraindication

The 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease explicitly states:

• Class III: Harm (Level of Evidence: C-LD): "In patients with PAD and congestive heart failure of any severity, cilostazol should not be administered" 1

This contraindication is based on:

1. Mechanism of action: Cilostazol is a phosphodiesterase III inhibitor. Other drugs in this class (like milrinone) have shown excess mortality in patients with heart failure with reduced ejection fraction 1

2. FDA black box warning: The FDA has mandated that cilostazol should not be used in patients with heart failure of any severity 1, 2

3. Mortality concerns: The contraindication exists due to concern for a potential class effect of phosphodiesterase inhibitors increasing mortality in heart failure patients 1

Clinical Presentation Analysis

The patient presents with:

• Intermittent pain and cramping in both legs when walking that resolves with rest (classic claudication symptoms)
• History of peripheral artery disease (PAD)
• Heart failure with reduced ejection fraction (HFrEF)

While cilostazol would typically be the first-line pharmacological therapy for PAD with intermittent claudication (improving walking distance by 40-60% after 12-24 weeks) 3, the patient's heart failure makes this medication unsafe.

Alternative Management Options

Since cilostazol is contraindicated, consider these alternatives:

1. Supervised exercise program: First-line non-pharmacological therapy for claudication

   • 30-45 minutes, 3 times weekly for 12 weeks
   • Significantly improves walking performance in PAD 4

2. Risk factor modification:

   • Aggressive management of diabetes
   • Optimization of blood pressure control
   • Lipid management
   • Smoking cessation if applicable

3. Antiplatelet therapy: For cardiovascular risk reduction (not claudication improvement)

   • Already likely on this given his cardiac history

4. Consider referral for revascularization: If symptoms are severely limiting quality of life and medical management is insufficient

Key Considerations

• Pentoxifylline is not recommended as an alternative as it has been shown to be ineffective for treatment of claudication (Class III: No Benefit, Level of Evidence: B-R) 1

• The bilateral nature of symptoms is typical for PAD and does not affect treatment decisions

• The history of prostate cancer is not relevant to the cilostazol contraindication

• The patient's claudication symptoms would likely benefit from cilostazol if not for the heart failure contraindication

Conclusion

The patient's friend's experience with cilostazol is not applicable to him due to the absolute contraindication in heart failure. Patient education about this important contraindication is essential, along with discussion of alternative management strategies focusing on supervised exercise programs and risk factor modification.