Musk Tongxin Dripping Pills for treating Ticagrelor in Patients After Percutaneous Coronary Intervention: Echocardiography Combined with Untargeted Metabolomics.

Lyu Nan,Zhao Jinxia,Guo Mengzhe,Lai Peng,Liang Jun,Geng Houfa,Wang Haibo

doi:10.3389/fphar.2021.731734

Abstract

Objectives: As current clinical practice guidelines, ticagrelor is the suggested therapeutic scheme to prevent adverse cardiovascular events in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI) treatment. However, this therapeutic strategy still fails, and around 30% patients display inadequate antiplatelet responses. Musk Tongxin Dripping Pill (MTDP) in Chinese hospital was usually considered as the combination with ticagrelor to improve the treatment effect. Unfortunately, the mechanism has not been elucidated. Methods: The untargeted metabolomic method was introduced based on liquid chromatography–high-resolution mass spectrometry (HPLC-HRMS) coupled with STI for the research of the drug combination mechanism between ticagrelor and MTDP. 28 patients with a confirmed diagnosis of AMI were selectively collected, who were then divided into two different dosage regimen groups, and the serum samples were collected for the untargeted metabolomics assay. Then the differential metabolites were associated with blood biochemical indicators. Results: The GLS values in both groups increased after treatment and those in the ticagrelor and MTDP combination group after treatment were higher than those in the ticagrelor group (p < 0.05), suggesting that the combination medication has better therapeutic effect on patients with myocardial infarction. From metabolomics analysis, the species of metabolites changed in two groups before and after treatment. Moreover, 93 differential metabolites changed in the drug combination group compared with the ticagrelor group after treatment (p < 0.05), which mainly related to changes in fatty acid metabolism pathways. Then the differential metabolites were found to be related with blood biochemical indicators, such as lipid, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Conclusion: This work will provide a possible mechanism of the drug combination interaction between ticagrelor and MTDP from two angles of echocardiography and metabonomics. Several potential metabolic pathways were also found to have a relationship with MTDP, which will provide a new perspective in clinical medication.

Highlights

Acute myocardial infarction (AMI) is myocardial necrosis caused by acute and persistent ischemia and hypoxia of the coronary artery (Liam et al, 2021)
The untargeted metabolomic method was introduced based on liquid chromatography–high-resolution mass spectrometry (HPLC-HRMS) coupled with speckle-tracking imaging (STI) for the research of the drug combination mechanism between ticagrelor and Musk Tongxin Dripping Pill (MTDP). 28 patients with a confirmed diagnosis of AMI were selectively collected, who were divided into two different dosage regimen groups, and the serum samples were collected for the untargeted metabolomics assay
The global longitudinal strain (GLS) values in both groups increased after treatment and those in the ticagrelor and MTDP combination group after treatment were higher than those in the ticagrelor group (p < 0.05), suggesting that the combination medication has better therapeutic effect on patients with myocardial infarction

Summary

Introduction

Acute myocardial infarction (AMI) is myocardial necrosis caused by acute and persistent ischemia and hypoxia of the coronary artery (Liam et al, 2021). As the development of this technique, the PCI is considered safe with the decrease of periprocedural complications, including the rates of associated stent thrombosis, Q-wave myocardial infarction, stroke, and death (Stephen et al, 2014). Frequent periprocedural myonecrosis can still be found through highly sensitive cardiac troponin assay (Reed et al, 2017). These periprocedural complications were often asymptomatic, they can delay hospital discharge and have been associated with an increased risk of future major cardiac adverse events, containing death (WarrenGash et al, 2009). The patients need antiplatelet therapy after surgery, which related to the prognosis of the patients

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