Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease - Results of the Optimizing antiPlatelet Therapy In diabetes MellitUS (OPTIMUS) study
Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease - Results of the Optimizing antiPlatelet Therapy In diabetes MellitUS (OPTIMUS) study
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DOI：
10.1161/circulationaha.106.667741
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发表时间：
2007-02-13
期刊：
影响因子：
37.8
通讯作者：
Costa, Marco A.
中科院分区：
文献类型：
--
作者：
Angiolillo, Dominick J.;Shoemaker, Steven B.;Costa, Marco A.
背景：2型糖尿病（T2 DM）患者接受氯吡格雷治疗后，血小板抑制作用较非糖尿病患者降低。在T2 DM患者中，增加氯吡格雷维持剂量是否可以增强血小板抑制作用尚不清楚。本试点研究的目的是评估功能的影响，高维持剂量的T2 DM患者与次优氯吡格雷诱导的antiplatelet effects.Methods和Results-T2 DM患者对慢性双重抗血小板治疗筛选，以确定次优氯吡格雷应答。后者被随机分配至30天的标准（75 mg; n = 20）或高（150 mg; n = 20）每日维持剂量治疗。在3个时间点评估血小板功能：基线、随机化后30天和恢复标准给药后30天。血小板功能参数包括二磷酸腺苷诱导（20和5 μ mol/L）的最大和晚期血小板聚集、血小板聚集抑制、血小板解聚和P2 Y（12）反应性指数。共筛选了64例T2 DM患者，以确定40例次优应答者。随机分组后，与75 mg组相比，150 mg组中二磷酸腺苷诱导的最大血小板聚集（20 μ mol/L）显著降低（P = 0.002;主要终点）。然而，在150 mg方案的患者中，60%的患者仍然存在次优的氯吡格雷反应。所有其他血小板功能参数显示，增强氯吡格雷诱导的抗血小板作用与150毫克，恢复后的标准dose.Conclusions基线值-一个150毫克的维持剂量的氯吡格雷与增强抗血小板作用相比，75毫克的高风险T2 DM患者。然而，增强的离体血小板反应性持续存在，其临床意义尚不清楚，需要在大规模临床试验中进行评估。
Background - After treatment with clopidogrel, patients with type 2 diabetes mellitus (T2DM) have reduced platelet inhibition compared with patients who are not diabetic. Whether platelet inhibition can be enhanced by increasing clopidogrel maintenance dosage in T2DM patients is unknown. The aim of this pilot study was to assess the functional impact of a high maintenance dose in T2DM patients with suboptimal clopidogrel-induced antiplatelet effects.Methods and Results - T2DM patients on chronic dual antiplatelet therapy were screened to identify suboptimal clopidogrel responders. The latter were randomized to 30-day treatment with a standard (75 mg; n = 20) or high (150 mg; n = 20) daily maintenance dose. Platelet function was assessed at 3 time points: baseline, 30 days after randomization, and 30 days after resuming standard dosing. Platelet function parameters included adenosine diphosphate-induced (20 and 5 mu mol/L) maximal and late platelet aggregation, inhibition of platelet aggregation, platelet disaggregation, and P2Y(12) reactivity index. A total of 64 T2DM patients were screened to identify 40 suboptimal responders. After randomization, maximal adenosine diphosphate-induced (20 mu mol/L) platelet aggregation was significantly reduced in the 150-mg group compared with the 75-mg group (P = 0.002; primary end point). However, suboptimal clopidogrel response was still present in 60% of patients on the 150-mg regimen. All other platelet function parameters showed enhanced clopidogrel-induced antiplatelet effects with 150 mg, which returned to baseline values after resumption of standard dosing.Conclusions - A 150-mg maintenance dose of clopidogrel is associated with enhanced antiplatelet effects compared with 75 mg in high-risk T2DM patients. However, enhanced ex vivo platelet reactivity continues to persist, the clinical implications of which are unknown and need to be evaluated in large-scale clinical trials.