Cilostazol significantly increased ACD at all measured time points and initial claudication distances at most time points. This agent may represent a new treatment option for patients with intermittent claudication.

Abstract-Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease. It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Cilostazol has been shown to improve walking distance in patients with IC. In addition to its reported vasodilator and antiplatelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy with 100 mg cilostazol BID, plasma triglycerides decreased 15% (PϽ0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) A1 (5.7%) significantly (PϽ0.001 and PϽ0.01, respectively). Both HDL 3 and HDL 2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL 2 . Individuals with baseline hypertriglyceridemia (Ͼ140 mg/dL) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment. In that subset of patients, HDL-C was increased 12.2% and triglycerides were decreased 23%. With cilostazol, there was a trend (3%) toward decreased apoB as well as increased apoA1, resulting in a significant (9.8%, PϽ0.002) increase in the apoA1 to apoB ratio. ilostazol is a vasodilator and platelet aggregation inhibitor that has been marketed since 1988 in Japan for treatment of ischemic symptoms of peripheral vascular disease. Cilostazol {6[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2-(1H)-quinolinone} is a 2-oxoquinolone derivative (molecular weight, 369.47) that has a plasma half-life of 10.5Ϯ4.4 hours after oral administration (Figure 1). Cilostazol inhibits both primary and secondary platelet aggregation in response to ADP, collagen, epinephrine, and arachidonic acid.1,2 The antiplatelet and vasodilator properties of cilostazol have been attributed to its ability to elevate intracellular levels of cAMP.3 Cilostazol is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Japanese studies performed in diabetic patients have indicated that, in addition to its vasodilator and antiplatelet properties, cilostazol may also favorably modify plasma lipoproteins by increasing HDL cholesterol (HDL-C) and reducing triglycerides. 4 The purpose of the present study was to determine whether cilostazol favorably modifies plasma lipoproteins in a general population of patients with stable IC. Methods Patient PopulationThe study included subjects with documented chronic, stable, symptomatic IC secondary to peripheral arterial disease (PAD). PAD was defined as an ankle-brachial index (ABI) Յ0.90; termination of walking on a variable-load, constant-speed treadmill due to IC (Ͼ54 and Ͻ805 m); and a Doppler-measured drop of Ն10 mm Hg in blood pressure of 1 ankle after the treadmill test. For patients without a qualifying ABI, a 20 -mm Hg drop in postexe...

Treatment with cilostazol was associated with greater improvements in community-based walking ability and HQL in patients with intermittent claudication than treatment with placebo. These improvements correlated with increased MWD. This analysis of effects of cilostazol on improving walking ability in persons with claudication is the first cilostazol study focused on community-based measures of functional status and HQL. Questionnaires assessing walking ability and HQL provide important patient-based information about clinical outcomes of claudication therapy.

Abstract:During exercise, patients with intermittent claudication (IC) have decreased limb arterial blood pressure that recovers during rest. A novel method for assessing dynamic recovery of function is measurement of the hemodynamic response after exercise. Cilostazol (Pletal  ), a new agent for the treatment of IC, increases walking distance and may decrease ischemic burden. The objective of this study was to assess the effect of cilostazol versus placebo on hemodynamic measurements after exercise-induced ischemia in patients with IC.Two double-blind, placebo-controlled studies with similar inclusion/exclusion criteria and duration (24 weeks) were pooled. Patients walked on a treadmill at 2.0 miles/h (3.2 km/h) on a 12.5% grade until the claudication-limited maximal walking distance (MWD) was reached. Anterior and posterior tibial pressures were measured with Doppler ultrasound at baseline and at 1, 5, and 9 min during recovery. Area under the curve (AUC), a measure of the time course of recovery of systolic pressure after exercise-induced ischemia, and ankle-brachial index (ABI) were calculated and compared using analysis of variance (ANOVA).All three treatment groups (308 patients randomized to cilostazol 100 mg bid, 303 to cilostazol 50 mg bid, and 299 to placebo) had similar baseline characteristics. Mean post-exercise AUC for cilostazol 100 mg and 50 mg bid versus placebo increased by 0.31 (p = 0.001) and 0.26 (p = 0.004), respectively. Mean resting ABI increased by 0.03 (p = 0.0039) and 0.04 (p = 0.0001) in the cilostazol 100 mg and 50 mg bid groups, respectively.In conclusion, following 24 weeks of treatment, cilostazol increased the ABI at rest and improved the recovery time of ankle pressures post-exercise.