糖尿病对行择期经皮冠状动脉介入治疗的肌钙蛋白阴性急性冠状动脉综合征患者替格瑞洛与氯吡格雷药效学影响的研究

Impact of Diabetes Mellitus on the Pharmacodynamic Effects of Ticagrelor Versus Clopidogrel in Troponin-Negative Acute Coronary Syndrome Patients Undergoing Ad Hoc Percutaneous Coronary Intervention.

机构信息

Icahn School of Medicine at Mount Sinai, New York, NY

University of Florida College of Medicine-Jacksonville, Jacksonville, FL.

出版信息

J Am Heart Assoc. 2017 Mar 29;6(4):e005650. doi: 10.1161/JAHA.117.005650.

BACKGROUND

Diabetes mellitus (DM) is associated with enhanced platelet reactivity and impaired response to oral antiplatelet therapy, including clopidogrel. This post hoc analysis investigated the pharmacodynamic effects of ticagrelor versus clopidogrel loading dose (LD) in troponin-negative acute coronary syndrome patients with or without DM undergoing percutaneous coronary intervention in the Ad Hoc PCI study.

METHODS AND RESULTS

Patients randomized (1:1) to receive ticagrelor 180 mg LD or clopidogrel 600 mg LD were assessed by diabetic status. Platelet reactivity (P2Y reaction units [PRU] on VerifyNow assay) was measured pre-LD, at 0.5, 2, and 8 hours post-LD, and at the end of the percutaneous coronary intervention. The primary endpoint was PRU levels 2 hours post-LD; secondary endpoints included rates of high on-treatment platelet reactivity (PRU≥208). Of 100 randomized patients, 51 received ticagrelor (DM, n=20; non-DM, n=31) and 49 clopidogrel (DM, n=16; non-DM, n=33). At 2 hours post-LD, mean (SD) PRU levels in DM patients were 130.1 (111.7) with ticagrelor versus 287.6 (71.9) with clopidogrel (mean [95%CI] difference -157.5 [-225.3, -89.8]; <0.001); in non-DM patients, they were 75.3 (75.7) versus 243.0 (72.4) (mean difference -167.7 [-207.1, -128.3]; <0.001). High on-treatment platelet reactivity rates at 2 hours post-LD were also significantly (<0.001) reduced with ticagrelor versus clopidogrel in DM and non-DM patients. Between-treatment differences for PRU and high on-treatment platelet reactivity were not significant at earlier time points but were at 8 hours post-LD (<0.001).

CONCLUSIONS

Compared with clopidogrel, ticagrelor achieved faster, enhanced platelet inhibition and reduced high on-treatment platelet reactivity rates, in DM and non-DM patients.

CLINICAL TRIAL REGISTRATION

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603082.

背景

糖尿病（DM）与血小板反应性增强和口服抗血小板治疗反应受损有关，包括氯吡格雷。本事后分析研究了在接受经皮冠状动脉介入治疗的急性冠状动脉综合征伴或不伴糖尿病的患者中，替格瑞洛与氯吡格雷负荷剂量（LD）相比的药效学作用，这些患者的肌钙蛋白均为阴性。

方法和结果

按糖尿病状态将接受替格瑞洛 180mg LD 或氯吡格雷 600mg LD 治疗的患者随机（1：1）分组。在 LD 前、LD 后 0.5、2 和 8 小时以及经皮冠状动脉介入治疗结束时，评估血小板反应性（VerifyNow 检测的 P2Y 反应单位[PRU]）。主要终点为 LD 后 2 小时的 PRU 水平；次要终点包括高治疗时血小板反应性（PRU≥208）的发生率。在 100 例随机患者中，51 例接受替格瑞洛（DM，n=20；非 DM，n=31），49 例接受氯吡格雷（DM，n=16；非 DM，n=33）。LD 后 2 小时，DM 患者替格瑞洛组的平均（SD）PRU 水平为 130.1（111.7），氯吡格雷组为 287.6（71.9）（平均[95%CI]差值-157.5[-225.3，-89.8]；<0.001）；非 DM 患者替格瑞洛组为 75.3（75.7），氯吡格雷组为 243.0（72.4）（平均差值-167.7[-207.1，-128.3]；<0.001）。LD 后 2 小时的高治疗时血小板反应性发生率也显著（<0.001）降低，与替格瑞洛相比，DM 和非 DM 患者的氯吡格雷降低。在更早的时间点，替格瑞洛和氯吡格雷之间的 PRU 和高治疗时血小板反应性差异没有统计学意义，但在 LD 后 8 小时时具有统计学意义（<0.001）。