Elam M B, Heckman J, Crouse J R, Hunninghake D B, Herd J A, Davidson M, Gordon I L, Bortey E B, Forbes W P
Departments of Pharmacology and Medicine, University of Tennessee Health Science Center and Veterans Affairs Medical Center, Memphis, Tennessee, USA.
Arterioscler Thromb Vasc Biol. 1998 Dec;18(12):1942-7. doi: 10.1161/01.atv.18.12.1942.
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) A1 (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.
西洛他唑是一种抗血小板药物和血管扩张剂，在日本被用于治疗周围血管疾病的缺血症状。目前它正在美国接受评估，用于治疗有症状的间歇性跛行（IC）。已证实西洛他唑可增加IC患者的步行距离。除了其报道的血管扩张和抗血小板作用外，西洛他唑还被认为对血浆脂蛋白有有益作用。我们研究了西洛他唑与安慰剂对189例IC患者血浆脂蛋白的影响。用100mg西洛他唑每日两次治疗12周后，血浆甘油三酯下降了15%（P<0.001）。西洛他唑还显著增加了血浆高密度脂蛋白胆固醇（HDL-C）（10%）和载脂蛋白（apo）A1（5.7%）（分别为P<0.001和P<0.01）。西洛他唑使HDL3和HDL2亚组分均增加；然而，HDL2的增加百分比最大。基线甘油三酯血症（>140mg/dL）的个体在接受西洛他唑治疗后，HDL-C和甘油三酯的变化最大。在该患者亚组中，HDL-C增加了12.2%，甘油三酯下降了23%。使用西洛他唑后，apoB有下降趋势（3%），同时apoA1增加，导致apoA1与apoB比值显著增加（9.8%，P<0.002）。低密度脂蛋白胆固醇和脂蛋白（a）浓度未受影响。西洛他唑治疗使跑步机行走时间增加了35%（P=0.0015），踝臂指数增加了9.03%（P<0.001）。这些结果表明，除了改善IC症状外，西洛他唑还能有利地改变外周动脉疾病患者的血浆脂蛋白。这种作用的机制目前尚不清楚。
