Can Cilostazol Increase Heart Rate?
Yes, cilostazol can increase heart rate through its mechanism as a phosphodiesterase III inhibitor that increases intracellular cyclic AMP, producing both vasodilatory effects and chronotropic (heart rate-increasing) effects.
Mechanism of Heart Rate Increase
Cilostazol increases intracellular cyclic adenosine monophosphate (cAMP) through PDE III inhibition, which accounts for its vasodilatory properties and cardiovascular effects including heart rate elevation 1.
The drug has been specifically used in clinical practice to increase heart rate in bradycardiac patients, demonstrating its direct chronotropic effects 2.
Clinical Evidence of Heart Rate Effects
In patients with bradycardiac atrial fibrillation, cilostazol administration significantly increased 24-hour total heartbeat counts from a mean of 69,685 beats (mean heart rate: 48 beats/min) to 87,352 beats (mean heart rate: 60 beats/min) 3.
The heart rate increase appears to be mediated by improved conductivity in the atrioventricular node and increased coronary blood supply from vessel dilation 3.
Common Cardiovascular Side Effects
Palpitations are among the most common side effects of cilostazol, along with headache, diarrhea, abnormal stools, and dizziness 4.
These palpitations likely reflect the drug's effect on heart rate and cardiac rhythm 1.
Critical Safety Considerations in High-Risk Populations
Absolute Contraindication in Heart Failure
Cilostazol is absolutely contraindicated in patients with heart failure of any severity due to increased risk of ventricular tachycardia and the class effect of PDE III inhibitors showing increased mortality in heart failure patients 1, 5, 6.
The FDA has mandated a black-box warning prohibiting cilostazol use in patients with congestive heart failure of any severity 4, 6.
Use in Coronary Artery Disease
Despite concerns about PDE III inhibitors, cilostazol demonstrates a different safety profile than other drugs in this class, particularly due to its adenosine uptake inhibition properties 2.
Cilostazol has mild coronary vasodilating effects with minimal hemodynamic impact, producing coronary artery dilation between 27-54% relative to nitroglycerin 7.
In patients with coronary artery disease without heart failure, cilostazol may actually reduce major coronary events (HR 0.38; 95% CI 0.17-0.86) and major adverse cardiovascular and cerebrovascular events (HR 0.47; 95% CI 0.23-0.96) 8.
Cardiac Effects Compared to Other PDE III Inhibitors
While cilostazol and milrinone both inhibit PDE III with similar potency in platelets, cilostazol elevates cAMP levels in cardiac ventricular myocytes to a significantly lesser extent than milrinone (p < 0.05) 9.
Cilostazol is less effective than milrinone in increasing left ventricular developed pressure and contractility, suggesting preferential action on vascular elements rather than direct cardiac effects 9.
Clinical Monitoring Recommendations
Evaluate patient tolerance at 2-4 weeks after initiation, as approximately 20% of patients discontinue cilostazol within the first 3 months due to side effects including cardiovascular symptoms 1, 10.
Monitor for symptoms of hypotension (dizziness, lightheadedness, syncope) and palpitations 1.
If cardiovascular side effects are intolerable at the standard 100 mg twice daily dose, consider dose reduction to 50 mg twice daily 1.
Key Clinical Pitfalls to Avoid
Never prescribe cilostazol to any patient with a history of heart failure, regardless of current functional status or ejection fraction 5, 10, 6.
Screen all patients for heart failure symptoms and signs before initiating therapy, as the black-box warning is based on class effect concerns 10.
The heart rate increase and palpitations, while common, should prompt evaluation to ensure the patient does not have underlying heart failure that was previously undiagnosed 1.