Cilostazol is Absolutely Contraindicated in Heart Failure
Cilostazol should never be used in patients with heart failure of any severity—it is explicitly contraindicated, not a treatment option. 1
Why Cilostazol is Contraindicated in Heart Failure
Class Effect and Mortality Risk
Cilostazol is a phosphodiesterase type III (PDE3) inhibitor, and other drugs in this class have demonstrated increased mortality in patients with heart failure with reduced ejection fraction. 2
The FDA has mandated a black box warning stating that cilostazol must not be used in patients with congestive heart failure of any severity due to the class effect of PDE3 inhibitors causing decreased survival compared to placebo in patients with Class III-IV heart failure. 1, 2
Several drugs with this same pharmacologic mechanism have caused decreased survival in heart failure patients, establishing a clear class-wide safety concern. 1
Mechanism of Harm
Cilostazol increases intracellular cyclic adenosine monophosphate (cAMP) levels through PDE3 inhibition, which can trigger ventricular tachycardia in patients with heart failure. 2
The increased cAMP levels have dangerous effects specifically in the heart failure population, particularly regarding ventricular arrhythmias. 2
Guideline Recommendations
Explicit Contraindication Across Guidelines
The American College of Cardiology and American Heart Association guidelines for peripheral artery disease explicitly state that cilostazol should not be administered to patients with PAD and congestive heart failure of any severity. 2, 3
When cilostazol is recommended for intermittent claudication in peripheral artery disease, guidelines consistently include the critical caveat: "in the absence of heart failure." 3
Clinical Evidence of Risk
A nationwide case-crossover study in diabetic patients found that cilostazol use was associated with a significantly 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 showed increased risk, with adjusted ORs ranging from 1.23 to 1.43, demonstrating the robustness of this finding. 4
Critical Screening Before Prescribing
Before prescribing cilostazol for any indication (such as intermittent claudication), clinicians must screen for:
- Any history of heart failure diagnosis of any severity (Class I-IV)
- Current symptoms suggesting heart failure (dyspnea, orthopnea, edema, reduced exercise tolerance)
- Prior documentation of reduced ejection fraction
- Any clinical signs of volume overload or cardiac decompensation 2
Alternative Approaches for Patients with Both PAD and Heart Failure
Supervised exercise therapy remains the first-line non-pharmacological treatment for claudication and should be prioritized in patients with heart failure. 2, 3
Exercise training should be performed for 30-45 minutes per session, at least 3 times weekly for a minimum of 12 weeks. 3
Pentoxifylline (400 mg three times daily) may be considered as a second-line pharmacological alternative, though its clinical effectiveness is marginal. 3
Endovascular procedures should be considered for patients with vocational or lifestyle-limiting disability when there is inadequate response to exercise therapy and a favorable risk-benefit ratio. 3
Common Pitfall to Avoid
The most critical error is prescribing cilostazol without adequately screening for heart failure. Even mild or asymptomatic heart failure (preserved or reduced ejection fraction) represents an absolute contraindication—there is no "safe" severity level for cilostazol use in heart failure patients. 1, 2