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

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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).

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Acknowledgements

We are grateful to Dr. Tian Kai Li, Dr. Hong Jie Xue, and Dr. Jing Yi Xue in the department of Cardiology, the First Affiliated Hospital, Harbin Medical University. The authors would like to acknowledge the department of Clinical Pharmacology of the First Affiliated Hospital, Harbin Medical University.

Contributor information

Guang Zhong Liu, Song Zhang, Dang Hui Sun, and Yue Li designed and conducted the experiment. Guang Zhang Liu, Song Zhang, and Dang Hui Sun analyzed the data and wrote the manuscript. Jing Shi, Wan Lan Bo, Wen Nan Wang, Chong Yang Zhang, Zhong Hua Wang, Wei Feng, Mei Jiao He, Yuan Yuan Liu, Shuang Li, and Lin Qun Zheng conducted the experiments. Guang Zhong Liu, Song Zhang, and Yue Li revised the manuscript. All authors approved the final version of the manuscript.

Funding

The study was funded by the National Nature Scientific Foundation of China (No. 81700305, No. 81300133, No. 81470462), the Fundamental Research Funds for the Provincial Universities of Heilongjiang (2017LCZX09), Heilongjiang Provincial Youth Innovative Talent Training Program(UNPYSCT-2017067), the Health Commission of Heilongjiang Province Research Project in China (Grant No. 2018072), and the Research Funds from the First Affiliated Hospital of Harbin Medical University (2017B006).

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Author notes

  1. Guang Zhong Liu, Song Zhang, and Dang Hui Sun are co-first authors and contributed equally to this article.

Authors and Affiliations

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

    Guang Zhong Liu, Song Zhang, Dang Hui Sun, Jing Shi, Wan Lan Bo, Wen Nan Wang, Chong Yang Zhang, Zhong Hua Wang, Wei Feng, Mei Jiao He, Yuan Yuan Liu, Shuang Li, Lin Qun Zheng & Yue Li

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

    Yue Li

  3. Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, 150001, Heilongjiang Province, China

    Yue Li

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Correspondence to Yue Li.

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The study was conducted in accordance with International Conference on Harmonization Guideline for Good Clinical Practice and Declaration of Helsinki and was approved in advance by the Ethics Committee of the First Affiliated Hospital of Harbin Medical University. All subjects provided written informed consents before their participation.

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Liu, G.Z., Zhang, S., Sun, D.H. et al. Half-dose ticagrelor versus high-dose clopidogrel in reducing platelet reactivity in acute coronary syndrome patients with high on-clopidogrel platelet reactivity (divide study). Eur J Clin Pharmacol 75, 1059–1068 (2019). https://doi.org/10.1007/s00228-019-02687-0

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