Angiolillo Dominick J, Capranzano Piera, Goto Shinya, Aslam Mohammed, Desai Bhaloo, Charlton Ronald K, Suzuki Yoshie, Box Lyndon C, Shoemaker Steven B, Zenni Martin M, Guzman Luis A, Bass Theodore A
Division of Cardiology, University of Florida College of Medicine at Shands Jacksonville, Jacksonville, FL 32209, USA.
Eur Heart J. 2008 Sep;29(18):2202-11. doi: 10.1093/eurheartj/ehn287. Epub 2008 Jun 21.
Patients with type 2 diabetes mellitus (T2DM) have reduced platelet inhibition compared with non-diabetics following P2Y(12) receptor blockade. Whether inhibition of P2Y(12) signalling can be enhanced by adjunctive treatment with cilostazol in T2DM patients is unknown. The aim of this pilot study was to assess the functional impact of cilostazol in T2DM patients on standard aspirin and clopidogrel treatment.
This was a prospective, double-blind, double-dummy, placebo-controlled, randomized, cross-over platelet function study. T2DM patients on dual antiplatelet therapy were assigned to receive cilostazol 100 mg or placebo twice daily for 14 days and afterwards crossed-over treatment assignments for another 14 days. Platelet function was performed at three time points: at baseline, 14 days after randomization, and 14 days after treatment cross-over. The P2Y(12) reactivity index, determined through flow cytometric assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein, was the primary endpoint measure. In addition to this flow cytometric evaluation, light transmittance aggregometry and VerifyNow testing were performed. A total of 25 T2DM patients were randomized; five patients discontinued treatment due to side effects. The P2Y(12) reactivity index was significantly lower following cilostazol treatment compared with placebo (36.3 +/- 20 vs. 59.9 +/- 16%; P = 0.0002). All other P2Y(12)-specific functional assessments showed enhanced inhibition of this signalling pathway following treatment with cilostazol.
Adjunctive treatment with cilostazol in T2DM patients on standard dual antiplatelet therapy enhances inhibition of platelet P2Y(12) signalling.
与非糖尿病患者相比，2型糖尿病（T2DM）患者在P2Y(12)受体阻断后血小板抑制作用降低。西洛他唑辅助治疗能否增强T2DM患者对P2Y(12)信号通路的抑制作用尚不清楚。本前瞻性研究旨在评估西洛他唑对接受标准阿司匹林和氯吡格雷治疗的T2DM患者血小板功能的影响。
这是一项前瞻性、双盲、双模拟、安慰剂对照、随机、交叉血小板功能研究。接受双联抗血小板治疗的T2DM患者被分配接受每日两次100 mg西洛他唑或安慰剂治疗，为期14天，之后交叉治疗方案再进行14天。在三个时间点检测血小板功能：基线时、随机分组后14天、治疗交叉后14天。通过流式细胞术评估血管舒张刺激磷蛋白磷酸化状态来测定P2Y(12)反应指数，这是主要终点指标。除了流式细胞术评估外，还进行了光透射聚集法和VerifyNow检测。共有25例T2DM患者被随机分组；5例患者因副作用停药。与安慰剂相比，西洛他唑治疗后P2Y(12)反应指数显著降低（36.3±20对59.9±16%；P=0.0002）。所有其他P2Y(12)特异性功能评估均显示，西洛他唑治疗后该信号通路的抑制作用增强。
在接受标准双联抗血小板治疗的T2DM患者中，西洛他唑辅助治疗可增强对血小板P2Y(12)信号通路的抑制作用。
