Cilostazol: improving walking distance in patients with intermittent claudication

Abstract

Intermittent claudication is a common, disabling symptom of peripheral arterial disease that limits walking distance and is associated with an increased cardiovascular risk of acute limb- or life-threatening complications. Very few patients with intermittent claudication (<7%) are suitable candidates for surgical revascularization, yet in contrast to the treatment of stable angina, few effective medical therapies (apart from exercise) are available for the symptomatic relief of intermittent claudication. The phosphodiesterase-3 inhibitor, cilostazol (Pletal, Otsuka Pharmaceuticals Ltd), is the first symptom-relieving treatment for intermittent claudication that has been evaluated successfully in large multicenter placebo-controlled, double-blind clinical trials (involving >2000 patients). A meta-analysis of the eight major efficacy studies with cilostazol has shown significant improvements in pain-free and maximum walking distance, and a good overall safety and tolerability profile. Thus, in the UK, USA and Japan, cilostazol administered at 100 mg twice daily is licensed for symptom relief in patients with stable, moderate-to-severe intermittent claudication, as an adjunct to nonpharmacological approaches such as exercise.

Long-Term Cilostazol Treatment and Predictive Factors on Outcomes of Endovascular Intervention in Patients with Diabetes Mellitus and Critical Limb Ischemia

“…It has a therapeutic focus on the inhibition of phosphodiesterase activity and suppression of cAMP degradation, resulting in increased cAMP in platelets and blood vessels and leading to inhibition of platelet aggregation and vasodilation [34]. Cilostazol is indicated for the treatment of intermittent claudication in patients with PAOD [35,36]. In recent years, cilostazol has been used for the secondary prevention of brain infarction through its antiplatelet antithrombotic effects [37].…”

“…In recent years, cilostazol has been used for the secondary prevention of brain infarction through its antiplatelet antithrombotic effects [ 37 ]. Furthermore, some studies have shown that cilostazol can prevent the proliferation of smooth muscle cells, consequently increasing peripheral blood flow and insulin sensitivity by reducing inflammation [ 35 , 38 ]. However, insufficient data are available to explain whether cilostazol increases the functional status of the involved lower extremities, improves primary patency in patients with CLI, as well as subsequent improvement in quality of life, and reduces the occurrence of adverse cardiovascular events and all-cause mortality.…”

Antiplatelet Agents

“…Cilostazol has shown improved cardiac safety in comparison to milrinone. In a meta-analysis of eight randomized, double-blind, placebo-controlled clinical trials, cilostazol increased pain-free walking by 67% and was better than pentoxifylline, the only other drug approved for PAD that works by different mechanisms [424].…”