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 t reatment of ischemic symptoms of peripheral vascular disease. It is current ly being evaluated in the United States for treatment of symptomatic interm ittent claudication (IC). Cilostazol has been shown to improve walking dist ance in patients with IC. In addition to its reported vasodilator and antip latelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo o n plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy wi th 100 mg cilostazol BID, plasma triglycerides decreased 15% (P<0.001). Cil ostazol 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 cilostazo l; however, the greatest percentage increase was observed in HDL2. Individu als with baseline hypertriglyceridemia (> 140 mg/dL) experienced the greate st changes in both HDL-C and triglycerides with cilostazol treatment. In th at subset of patients, HDL-C was increased 12.2% and triglycerides were dec reased 23%. With cilostazol, there was a trend (3%) toward decreased apoB a s well as increased apoA1, resulting in a significant (9.8%, P<0.002) incre ase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lip oprotein(a) concentrations were unaffected. Cilostazol treatment resulted i n 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.