Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication

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% (P<0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) Al1(5.7%) significantly (P<0.001 and P<0.01, respectively). Both HDL3 and HDL2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL2. Individuals with baseline hypertriglyceridemia (> 140 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%, P<0.002) increase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lipoprotein(a) concentrations were unaffected. Cilostazol treatment resulted in a 35% increase in treadmill walking time (P=0.0015) and a 9.03% increase in ankle-brachial index (P<0.001). These results indicate that in addition to improving the symptoms of IC, cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease. The mechanism of this effect is currently unknown.