Clinical Efficacy and Safety of Cilostazol: A Critical Review of the Literature

Abstract

Cilostazol is a unique antiplatelet agent that has been commercially available for over two decades. As a phosphodiesterase III inhibitor, it reversibly inhibits platelet aggregation yet also possesses vasodilatory and antiproliferative properties. It has been widely studied in a variety of disease states, including peripheral arterial disease, cerebrovascular disease, and coronary artery disease with percutaneous coronary intervention. Overall, cilostazol appears to be a promising agent in the management of these disease states with a bleeding profile comparable to placebo; even when combined with other antiplatelet agents, cilostazol does not appear to increase the rate of bleeding. Despite the possible benefit of cilostazol, its use is limited by tolerability as some patients often report drug discontinuation due to headache, diarrhea, dizziness, or increased heart rate. To date, it has been predominantly studied in the Asian population, making it difficult to extrapolate these results to a more diverse patient population. This paper discusses the evolving role of cilostazol in the treatment of vascular diseases.

Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation

“…Trequinsin, another PDE3 inhibitor, also inhibits thrombin-induced activation of equine platelets (18–20), however, to our knowledge, this is the first study testing cilostazol for platelet inhibitory effects in horses. Of the two tested PDE inhibitors, only cilostazol has been used as a thromboprophylactic drug in humans (34), with IBMX being largely an in vitro or ex vivo experimental tool. Since we and others have shown that the weaker non-selective PDE inhibitors, theophylline and pentoxifylline, are ineffective at inhibiting platelet activation when administered to horses (see text footnote 1) or tested ex vivo (20, 35), cilostazol has potential as a PDE inhibitor in horses.…”

Drugs That May Cause or Exacerbate Heart Failure

“…185 A selective inhibitor of phosphodiesterase type 3, it is believed to heighten the risk of fatal arrhythmias in patients with HF. It has never been directly studied in patients with HF; however, the increased risk is presumed to occur within 1 month of initiation because of the nature of the observed electrophysiological effects and extrapolation from the effects of oral milrinone, a pharmacologically similar medication.…”

Cilostazol Is Useful for the Treatment of Sinus Bradycardia and Associated Hemodynamic Deterioration Following Heart Transplantation

“…The major side effect of cilostazol is bleeding, due to its antiplatelet activity, although its risk is low. 14) Our patient did not suffer from any side effects from cilostazol during the course.…”