Cilostazol is Absolutely Contraindicated in Heart Failure
Cilostazol should not be administered to patients with heart failure of any severity due to the increased mortality risk associated with phosphodiesterase III inhibitors in this population. 1, 2
Mechanism of Contraindication
Cilostazol is a phosphodiesterase type III (PDE3) inhibitor that increases intracellular cyclic adenosine monophosphate (cAMP) levels, providing vasodilatory and antiplatelet effects. 3
Other phosphodiesterase III inhibitors (specifically oral milrinone) have demonstrated excess mortality in patients with heart failure with reduced ejection fraction, raising concerns about a potential class effect. 1
The elevated cAMP levels from PDE3 inhibition can trigger ventricular tachycardia and other dangerous cardiac effects in heart failure patients. 3
Regulatory and Guideline Positions
The FDA has issued a black box warning explicitly stating that cilostazol is contraindicated in patients with congestive heart failure of any severity. 2
The 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for peripheral artery disease provides a Class III: Harm recommendation, stating that cilostazol should not be administered in patients with PAD and congestive heart failure of any severity. 1
This contraindication applies to heart failure of any severity, not just advanced stages (Class III-IV), due to the demonstrated mortality risk with this drug class. 1, 2
The evidence supporting this contraindication is based on studies showing decreased survival with phosphodiesterase III inhibitors compared to placebo in heart failure patients. 1
Real-World Evidence Supporting the Contraindication
A 2018 nationwide case-crossover study in diabetic patients found that cilostazol use was associated with a 35% increased risk of hospitalization for heart failure (adjusted OR: 1.35,95% CI: 1.14-1.59). 4
Sensitivity analyses using different control periods consistently demonstrated increased risk, with adjusted ORs ranging from 1.23 to 1.43, confirming the robustness of this association. 4
A 2024 pharmacovigilance study of the FDA FAERS database identified cardiac failure as the most frequently reported adverse event with cilostazol, with cardiac disorders representing the highest number of positive risk signals (53 cardiovascular-related adverse events identified). 5
Clinical Screening Requirements
Before prescribing cilostazol for peripheral artery disease or claudication, clinicians must:
Screen all patients for any history of heart failure, including heart failure with preserved ejection fraction (HFpEF), as the contraindication applies to all types and severities. 1, 2
Assess for symptoms suggestive of heart failure including dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, peripheral edema, and exercise intolerance. 1
Review prior echocardiographic data if available to identify any degree of systolic or diastolic dysfunction. 1
Avoid cilostazol in patients with active pathologic bleeding or hemostatic disorders, as this represents an additional absolute contraindication. 2
Alternative Management for PAD Patients with Heart Failure
For patients with both peripheral artery disease and heart failure who require treatment for claudication:
Supervised exercise therapy remains the first-line non-pharmacological treatment and should be prioritized. 3
Pentoxifylline is not recommended as an alternative, as it has shown no benefit for treatment of claudication in patients with chronic symptomatic PAD (Class III: No Benefit recommendation). 1
Risk factor modification including smoking cessation, lipid management, blood pressure control, and antiplatelet therapy (aspirin or clopidogrel) should be optimized. 6
For patients requiring revascularization, endovascular or surgical interventions should be considered without cilostazol adjunctive therapy. 1