Effects of cilostazol in the heart

Abstract

Cilostazol is a selective phosphodiesterase 3 (PDE3) inhibitor approved by the Food and Drug Administration for treatment of intermittent claudication. It has also been used in bradyarrhythmic patients to increase heart rates. Recently, cilostazol has been shown to prevent ventricular fibrillation in patients with Brugada syndrome. Cilostazol is hypothesized to suppress transient outward potassium (Ito) current and increase inward calcium current, thus, maintaining the dome (phase 2) of action potential, decreasing transmural dispersion of repolarization and preventing ventricular fibrillation. Although many PDE3 inhibitors have been shown to increase cardiac arrhythmia in heart failure, cilostazol has presented effects that are different from other PDE3 inhibitors, especially adenosine uptake inhibition. Owing to this effect, cilostazol could be an effective cardioprotective drug, with its beneficial effects in preventing arrhythmia. In this review, the cardiac electrophysiological effects of cilostazol are presented and its possible cardioprotective effects, particularly in preventing ventricular fibrillation, are discussed, with emphasis on the need to further verify its clinical benefits.

Effect of a 4-Week Treatment with Cilostazol in Patients with Chronic Tinnitus: A Randomized, Prospective, Placebo-controlled, Double-blind, Pilot Study

“…Moreover, cAMP-dependent signaling is expected from animal studies to have neuroprotective effects in the cochlea [23,24] . PDE, the enzyme that hydrolyzes cGMP and cAMP to their inactive forms, has been classified into 11 isoenzymes [25] . PDE3 has high affinity for both cGMP and cAMP, and cAMP hydrolysis by PDE3 is 10 times greater than cGMP hydrolysis in terms of amount [25] .…”

“…PDE, the enzyme that hydrolyzes cGMP and cAMP to their inactive forms, has been classified into 11 isoenzymes [25] . PDE3 has high affinity for both cGMP and cAMP, and cAMP hydrolysis by PDE3 is 10 times greater than cGMP hydrolysis in terms of amount [25] . Cilostazol is a selective PDE3 inhibitor and mainly increases the amount of cAMP by inhibiting cAMP degradation.…”

Cilostazol to Overcome High On-Treatment Platelet Reactivity in Korean Patients Treated With Clopidogrel and Calcium-Channel Blocker

“…This unique feature may contribute to the observed safety profile of cilostazol, and several studies have suggested a beneficial effect of cilostazol in arrhythmia prevention. 6 In this issue of the Journal, Lee et al provide more evidence regarding the benefit of adding cilostazol to DAPT ["triple antiplatelet therapy" (TAPT)] in reducing post-PCI clinical events. 7 In the primary analysis of the CILON-T (influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stent implantation) trial, 8 TAPT did not show superiority in reducing the composite of adverse cardiovascular outcomes after drug-eluting stent implantation despite greater reduction in platelet reactivity assessed by the VerifyNow P2Y12 assay [~45 P2Y12 reaction units (PRU)] compared with DAPT.…”

A Randomized Comparison Study Assessing the Impact of Cilostazol on the Heart Rate and Arrhythmias by 24-Hour Ambulatory Holter Electrocardiographic Monitoring after Drug-Eluting Stent Implantation for Coronary Artery Disease

“…Third, cilostazol causes systemic vasodilation, thus producing reflex adrenergic stimulation 14) . Finally, cilostazol may cause a positive chronotropic effect due to its inhibitory effects on adenosine uptake 21) or its antagonizing adenosine tri- Data are given as medians (interquartile range), n (%) or mean differences (95% CI). Log-transformed data HR heart rate p 0.05 (compared with dual antiplatelet therapy), p 0.05 (compared with the baseline within-group).…”