Can Cilostazol Increase Heart Rate?
Yes, cilostazol can increase heart rate through its vasodilatory mechanism as a phosphodiesterase III inhibitor, and this effect has been documented in clinical studies, particularly in patients with bradyarrhythmias.
Mechanism of Heart Rate Effects
Cilostazol increases intracellular cyclic AMP (cAMP) through PDE III inhibition, which produces vasodilatory effects that can reflexively increase heart rate 1.
The drug has been specifically used in bradyarrhythmic patients to therapeutically increase heart rates, demonstrating its chronotropic properties 2.
Clinical Evidence of Heart Rate Increase
In patients with bradycardiac atrial fibrillation, cilostazol administration increased 24-hour total heartbeat counts from a mean of 69,685 (48 beats/min) to 87,352 (60 beats/min), representing a clinically significant increase in heart rate 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.
Cardiovascular Side Effects Profile
Palpitations are listed as one of the most common cardiovascular side effects of cilostazol, along with dizziness, which are consistent with its heart rate-increasing effects 4, 1.
Approximately 20% of patients discontinue cilostazol within the first 3 months due to side effects, including cardiovascular effects such as palpitations 1, 5.
Critical Safety Considerations in High-Risk Populations
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 6, 7.
The FDA has mandated a black-box warning prohibiting cilostazol use in patients with congestive heart failure of any severity 4, 7.
Despite concerns about PDE III inhibitors as a class, cilostazol has shown minimal increase in cardiac adverse events compared to placebo in patients without heart failure, with cardiovascular death occurring in 0.6% of cilostazol-treated patients versus 0.5% with placebo in over 2000 patients followed for up to 6 months 4.
Differential Cardiac Effects Compared to Other PDE III Inhibitors
While cilostazol and milrinone both inhibit PDE3, cilostazol elevates cAMP levels in cardiac ventricular myocytes to a significantly lesser extent than milrinone (p < 0.05), resulting in less potent cardiotonic effects 8.
Cilostazol is less effective than milrinone in increasing left ventricular developed pressure and contractility, which may explain its relatively safer cardiac profile in patients without heart failure 8.
Monitoring Recommendations
Evaluate patient tolerance at 2-4 weeks after initiation, specifically monitoring for palpitations, dizziness, lightheadedness, or syncope that may indicate excessive heart rate increase or hypotension 1, 5.
If significant cardiovascular side effects occur, consider dose reduction from 100 mg twice daily to 50 mg twice daily 1.
Screen all patients for any history or symptoms of heart failure before prescribing, as the contraindication applies regardless of ejection fraction or heart failure severity 6, 5.
Clinical Context for Older Adults with Vascular Disease
In patients with coronary artery disease without heart failure, cilostazol has demonstrated beneficial effects including risk reduction for major coronary events (HR 0.38,95% CI 0.17-0.86) and lower risk of angina pectoris 9.
The heart rate increase from cilostazol should be distinguished from dangerous arrhythmias—the drug has actually been shown to prevent ventricular fibrillation in Brugada syndrome patients by suppressing transient outward potassium current 2.