From the Guidelines
Cilostazol is contraindicated in patients with heart failure due to its potential to increase mortality and worsen heart failure symptoms, as evidenced by the most recent guidelines from the American College of Cardiology/American Heart Association 1. The primary concern with using cilostazol in heart failure patients is its mechanism of action as a phosphodiesterase-3 (PDE3) inhibitor, which increases cyclic adenosine monophosphate (cAMP) levels in cardiac tissue, leading to increased cardiac contractility and heart rate. While these effects might seem beneficial, they actually increase myocardial oxygen demand and workload on an already compromised heart. Key points to consider when evaluating the use of cilostazol in patients with heart failure include:
- The potential for increased mortality and worsening of heart failure symptoms, as noted in the 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease 1
- The FDA's black box warning specifically prohibiting the use of cilostazol in patients with heart failure of any severity class (NYHA Classes I-IV)
- Alternative medications like aspirin, clopidogrel, or pentoxifylline that should be considered for patients with both heart failure and conditions for which cilostazol would typically be indicated It is essential to prioritize the most recent and highest-quality evidence when making clinical decisions, and in this case, the 2024 guideline 1 provides the most up-to-date recommendations for the management of lower extremity peripheral artery disease, including the use of cilostazol in patients with heart failure. The contraindication of cilostazol in heart failure patients is further supported by earlier studies, such as the 2012 American College of Chest Physicians evidence-based clinical practice guidelines 1 and the 2017 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease 1, which also highlight the potential risks and limitations of using cilostazol in this population.
From the FDA Drug Label
Cilostazol and several of its metabolites are inhibitors of phosphodiesterase III. Several drugs with this pharmacologic effect have caused decreased survival compared to placebo in patients with class III-IV congestive heart failure. Cilostazol tablets are contraindicated in patients with congestive heart failure of any severity.
- Cilostazol is contraindicated in heart failure because it is a phosphodiesterase III inhibitor, and drugs with this effect have been associated with decreased survival in patients with congestive heart failure, particularly those with class III-IV heart failure 2.
- The contraindication applies to heart failure of any severity.
From the Research
Cilostazol Contraindication in Heart Failure
- Cilostazol, a phosphodiesterase 3 inhibitor, is contraindicated in patients with congestive heart failure due to its potential to exacerbate the condition 3, 4.
- The exact mechanism of this contraindication is not fully understood, but it is thought to be related to the drug's effects on cardiac function and its potential to increase the risk of ventricular arrhythmias 5, 6.
- Studies have shown that cilostazol can increase the risk of heart failure hospitalization in patients with diabetes, with an adjusted odds ratio of 1.35 (95% CI: 1.14-1.59) 7.
- The drug's effects on the heart are complex and may involve the suppression of transient outward potassium current and the increase of inward calcium current, which can maintain the dome of the action potential and prevent ventricular fibrillation 6.
- However, despite these potential benefits, the risk of heart failure associated with cilostazol use outweighs its potential benefits in patients with congestive heart failure, leading to its contraindication in this population 3, 4, 7.