Gut microbiota induces high platelet response in patients with ST segment elevation myocardial infarction after ticagrelor treatment

Abstract

Background:Ticagrelor is a first-line drug for the treatment of acute ST elevation myocardial infarction (STEMI). However, approximately 20% STEMI patients taking ticagrelor exhibited a delayed response and the mechanism was still unclear.Methods:To explore the mechanism of the poor response of ticagrelor in post-percutaneous coronary intervention (PCI) patients, we enrolled 65 high platelet reactivity (HPR) patients and 90 controls (normal platelet reactivity [NPR]). Pharmacokinetic assessment result showed that the plasma concentrations of ticagrelor and its metabolism production, AR-C124910XX, were lower in HPR patients than controls. Further single nucloetide polymorphism (SNP) analysis identified that there is no difference in ATP binding cassette subfamily B member 1 (ABCB1) gene expression between the NPR group and the HPR group. Metagenomic and metabolomic analyses of fecal samples showed that HPR patients had higher microbial richness and diversity. Transplantation of the gut microbiota from HPR donors to microbiota-depleted mice obviously decreased plasma concentration of ticagrelor.Results:Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with STEMI and support that modify gut microbiota is a potential therapeutic option for STEMI.Conclusions:Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with ST elevation myocardial infarction (STEMI) and support that modify gut microbiota is a potential therapeutic option for STEMIFunding:NSFC 82170297 and 82070300 from the National Natural Science Foundation of China.

Associations of Gut Microbiota and Fatty Metabolism With Immune Thrombocytopenia

“…More than 20% metabolites were significantly associated with platelet activation markers and the majority involved lipids. In a more recent study, clinical findings with experimental data suggested that gut microbiota dysbiosis may be an important mechanism for the high platelet reactivity in patients treated with ticagrelor, a first-line drug for the treatment of acute ST elevation myocardial infarction ( 16 ). For example, the abundance of gut microbiota species Methylbacillus , Sphingomonas , and Staphylococcus was negatively correlated with serum salicylate, which was previously found to induce ITP and inhibit platelet production in megakaryocytes ( 17 ).…”

Editorial: Impact of the gut microbiota on cardiovascular medicine

“…A number of metaorganismal circuits have been reported to modulate different aspects of cardiovascular and cardiometabolic conditions, such as arterial hypertension and hypertensive end organ damage ( 3 , 4 ), lipid metabolism and atherosclerosis ( 5 , 6 ), glucose metabolism ( 7 ), platelet activation and thrombus formation ( 8 – 10 ), and ischemic heart disease ( 11 ). Remarkably, recent studies suggest that gut microbial composition also impacts on the efficacy of cardiovascular pharmacotherapy ( 12 , 13 ). Targeting of distinct gut microbial pathways may help to establish novel strategies in preventing cardiometabolic and cardiovascular diseases.…”

Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis

“…Intriguingly, gut microbial diversity might even affect cardiovascular disease therapies as shown for ticagrelor by a recent study on the efficacy of anti-platelet treatment in STEMI (113). Moreover, it was shown that chronic statin therapy is linked to lower prevalence of microbiota dysbiosis (109,110). In addition to above, abnormal gut microbiome homeostasis could be linked to development of chronic effects from viral infections (111).…”