A randomized study assessing the impact of cilostazol on platelet function profiles in patients with diabetes mellitus and coronary artery disease on dual antiplatelet therapy: results of the OPTIMUS-2 study
A randomized study assessing the impact of cilostazol on platelet function profiles in patients with diabetes mellitus and coronary artery disease on dual antiplatelet therapy: results of the OPTIMUS-2 study
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DOI：
10.1093/eurheartj/ehn287
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发表时间：
2008-09-01
影响因子：
39.3
通讯作者：
Bass, Theodore A.
中科院分区：
文献类型：
--
作者：
Angiolillo, Dominick J.;Capranzano, Piera;Bass, Theodore A.
目的应用P2Y(12)受体阻断剂后，2型糖尿病(T2 DM)患者与非糖尿病患者相比，其血小板抑制程度明显降低。在T2 DM患者中，是否可以通过西洛他唑的辅助治疗来增强对P2Y(12)信号的抑制作用尚不清楚。这项先导性研究的目的是评估西洛他唑在标准阿司匹林和氯吡格雷治疗的T2 DM患者中对功能的影响。方法和结果这是一项前瞻性、双盲、双模拟、安慰剂对照、随机、交叉的血小板功能研究。接受双重抗血小板治疗的T2 DM患者被分配给西洛他唑100 mg或安慰剂，每天两次，持续14天，然后交叉治疗14天。在三个时间点：基线、随机后14天和治疗交叉后14天进行血小板功能测定。通过流式细胞术评估血管扩张剂刺激的磷蛋白的磷酸化状态来确定的P2Y(12)反应性指数是主要的终点测量。除了这项流式细胞术评估外，还进行了透光率聚集和VerifyNow测试。共有25名T2 DM患者被随机分组；5名患者因副作用而停止治疗。与安慰剂组相比，西洛他唑治疗组的P2Y(12)反应性指数显著降低(36.3%+/-20vs.59.9+/-16%；P=0.0002)。所有其他针对P2Y(12)的功能评估显示，西洛他唑治疗后对这一信号通路的抑制作用增强。结论在标准的双重抗血小板治疗的基础上，西洛他唑辅助治疗T2 DM患者可增强对血小板P2Y(12)信号的抑制作用。
Aims 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.Methods and results 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.Conclusion Adjunctive treatment with cilostazol in T2DM patients on standard dual antiplatelet therapy enhances inhibition of platelet P2Y(12) signalling.