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Gut microbiota induces high platelet response in patients with ST-segment elevation myocardial infarction after ticagrelor treatment
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  • Xi Zhang,
  • Xiaolin Zhang,
  • Fangnian Tong,
  • Yi Cai,
  • Yujie Zhang,
  • Haixu Song,
  • Xiaoxiang Tian,
  • Chenghui Yan,
  • Yaling Han
Xi Zhang
Shengjing Hospital of China Medical University
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Xiaolin Zhang
General Hospital of Northern Theatre command
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Fangnian Tong
General Hospital of Northern Theatre command
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Yi Cai
General Hospital of Northern Theatre command
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Yujie Zhang
General Hospital of Northern Theatre command
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Haixu Song
General Hospital of Northern Theatre command
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Xiaoxiang Tian
General Hospital of Northern Theatre command
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Chenghui Yan
General Hospital of Northern Theatre command
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Yaling Han
Shengjing Hospital of China Medical University

Corresponding Author:[email protected]

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Abstract

Aims: Ticagrelor has become a new antiplatelet drug recommended by the acute coronary syndrome guidelines. Several studies have shown that high platelet reactivity occurs in ST-segment elevation myocardial infarction (STEMI) patients after taking ticagrelor. Here, we investigated whether gut microbiota play an important role in the change of platelet reactivity. Methods and Results: The rate of platelet aggregation (PA) was measured using light transmittance aggregometry. Pharmacokinetic assessment was used to analyze the plasma concentration of ticagrelor and its main active metabolite AR-C124910XX. Patients were classified into the normal platelet reactivity group (NPR) and high platelet reactivity group (HPR) according to PA at 2h after ticagrelor administration. High-throughput sequencing and 1H NMR profiling were used to investigate gut microbiota characteristics in patients. Finally, we transplanted the microbiota gut of patients into two groups of sterile mice to verify its effect on platelet reactivity. PA of HPR was higher than that of NPR at each time point after ticagrelor administration. The plasma concentrations of ticagrelor and AR-C124910XX were lower in HPR than in NPR. The diversity of gut microflora in HPR was greater than that in NPR. Through fecal transplantation high platelet reactivity could be transmitted to sterile mice. Conclusions: Gut microbiota variance and their metabolism between HPR and NPR may be an important mechanism for the difference in PA after ticagrelor administration. Gut microbiota could help improve our understanding of the pathogenesis of high platelet reactivity and support the potential therapeutic options that modify gut microbiota.