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替格瑞洛半量与高剂量氯吡格雷降低氯吡格雷高反应性急性冠脉综合征患者血小板反应性(DIVIDE 研究)。

Half-dose ticagrelor versus high-dose clopidogrel in reducing platelet reactivity in acute coronary syndrome patients with high on-clopidogrel platelet reactivity (divide study).

机构信息

Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Youzheng Street 23#, Nangang District, Harbin, 150001, Heilongjiang Province, China.

Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University, Harbin, 150001, Heilongjiang Province, China.

出版信息

Eur J Clin Pharmacol. 2019 Aug;75(8):1059-1068. doi: 10.1007/s00228-019-02687-0. Epub 2019 May 12.

Abstract

PURPOSE

High on-treatment platelet reactivity (HTPR) after clopidogrel administration in patients with acute coronary syndrome (ACS) has been associated with an increased risk of adverse events. Our previous studies reported that half-dose ticagrelor provides a similar inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation as standard-dose ticagrelor, but half-dose of ticagrelor has not been studied in Chinese ACS patients with HTPR. This study aimed to compare the antiplatelet action of half-dose ticagrelor with high-dose clopidogrel in ACS patients with HTPR.

METHODS

In this single-center randomized controlled trial, 80 (of 418 screened, 19.13%) ACS patients with HTPR while on clopidogrel were randomized to either half-dose ticagrelor (90 mg LD, then 45 mg twice daily) or high-dose clopidogrel (150 mg once daily). Platelet function was assessed by thromboelastography (TEG) and light transmission aggregometry (LTA), and adverse events were monitored throughout the study for 30 days.

RESULTS

The ADP-induced platelet inhibition rate (IR) as measured by TEG was significantly higher for half-dose ticagrelor compared with high-dose clopidogrel (70.40% [61.10%-91.70%] vs. 44.25% [34.67%-79.07%], p = 0.001). The repeated HTPR rate was dramatically higher for high-dose clopidogrel compared with half-dose ticagrelor (6 of 32, 18.75% vs. 1 of 35, 2.85%; p = 0.04). No patients in either treatment group exhibited a major bleeding event or other adverse events.

CONCLUSIONS

In ACS patients with HTPR, half-dose ticagrelor is more effective than high-dose clopidogrel in reducing platelet reactivity (NCT03062462).

摘要

目的

氯吡格雷治疗后血小板高反应性(HTPR)与急性冠状动脉综合征(ACS)患者的不良事件风险增加相关。我们之前的研究报告称,半剂量替格瑞洛对二磷酸腺苷(ADP)诱导的血小板聚集的抑制作用与标准剂量替格瑞洛相似,但尚未在 HTPR 的中国 ACS 患者中研究过半剂量替格瑞洛。本研究旨在比较 HTPR 的 ACS 患者中半剂量替格瑞洛与高剂量氯吡格雷的抗血小板作用。

方法

在这项单中心随机对照试验中,筛选出的 418 例 ACS 患者中有 80 例(19.13%)为 HTPR,这些患者正在服用氯吡格雷,随机分为半剂量替格瑞洛组(90mgLD,然后 45mg 每日两次)或高剂量氯吡格雷组(150mg 每日一次)。通过血栓弹力图(TEG)和光传输聚集度测定法(LTA)评估血小板功能,并在整个研究期间监测 30 天的不良事件。

结果

TEG 测量的 ADP 诱导的血小板抑制率(IR)对半剂量替格瑞洛明显高于高剂量氯吡格雷(70.40%[61.10%-91.70%] vs. 44.25%[34.67%-79.07%],p=0.001)。高剂量氯吡格雷的反复 HTPR 发生率明显高于半剂量替格瑞洛(6 例/32 例,18.75% vs. 1 例/35 例,2.85%;p=0.04)。两组均无患者发生大出血事件或其他不良事件。

结论

在 HTPR 的 ACS 患者中,半剂量替格瑞洛在降低血小板反应性方面比高剂量氯吡格雷更有效(NCT03062462)。

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