The Study On The Platelets High Reactivity In Patients With ST-segment Elevation Myocardial Infarction After Treatment With Ticagrelor

ObjectiveCurrently,the combination of aspirin and P2Y₁₂2 receptor antagonist dual antiplatelet therapy is a basic treatment of ACS,which can significantly reduce the incidence of serious adverse cardiovascular events in ACS patients..As a new type of P2Y₁₂ receptor inhibitor,ticagrelor has become a recommended antiplatelet therapy drug for ACS treatment guidelines at home and abroad.With the wide application of ticagrelor,its antiplatelet effect is still the research focus.Therefore,this study aims to analyze the pharmacokinetics and pharmacodynamics of ticagrelor in the acute ST-elevation myocardial infarction population of northern Han population.Through its indicators analyze the effect of ticagrelor on STEMI,and explain the phenomenon of platelet high reactivity after treatment.At present,the role of intestinal flora in the occurrence and development of diseases is gradually concerned.The influence of intestinal flora disorder and bacterial metabolites abnormality on disease has become the current research hotspot.More and more studies have shown that and intestinal flora plays an important role in atherosclerotic diseases.Therefore,the aim of this study is exploring the causes of platelet high reactivity in STEMI patients after ticagrelor treated by the intestinal flora.MethodsA total of 155 patients with acute ST-segment elevation myocardial infarction who were treated at chest pain center of General Hospital of Shenyang Military Region were enrolled from April 2016 to March 2018.All patients take orally 180mg loading dose of ticagrelor before the percutaneous coronary intervention.On the basis of platelet aggregation rate which is detected after taking drug 2h by light turbidimetry,the patients were divided into normal reactivity group and high reactivity group.The general clinical data of the patients were recorded,and extracted selected patients venous blood before?0h?and after taking ticagrelor?2h,4h,6h,8h,12h and 24h?.The concentration of ticagrelor and its main metabolite AR-C124910XX in two groups at each time point was detected,and the platelet aggregation rate of two groups was detected by light turbidimetry.The 155 patients with STEMI were followed up for30 days.The follow-up endpoint were major adverse cardiac and cerebral events?MACCE?,including all-causes of death,recurrent myocardial infarction,heart failure and stroke.Observe and compare the difference in the incidence of MACCE events between the two groups.At the same time,intestinal flora DNA were extracted from fecal samples of two groups The hypervariable region of16S rDNA was amplified by high-throughput sequencing to observe the composition and distribution of intestinal flora in two groups,and to analyze the intestinal microbial diversity to compare the differences bacteria genera between the two groups.ResultsThe patients were grouped according to the 2h platelet aggregation rate after taking ticagrelor,90 in the normal reactivity group,and 65 in the high reactivity group.The clinical baseline data of the two groups had no significant difference?P>0.05?.The platelet aggregation at each time point by light turbidimetry in high reactivity group were higher than the normal reactivity group,and the platelet aggregation has significant difference in 2h 4h,6h and8h?P<0.05?.The blood concentration of ticagrelor in high reactivity group was lower than that in the normal reactivity group at each time point after taking medicine,and there was a significant difference in the concentration of ticagrelor between the two groups in 2h,4h,6h and 8h?P<0.05?.The plasma concentration of AR-C124910XX in the high reactivity group gradually increased within 24h,and the plasma concentration in 12h was lower than that in the normal reactivity group.There was a significant difference in AR-C124910XX blood concentration between the two groups after taking medicine,2h,4h,6h and 8h?P<0.05?.The incidence of MACCE events in 30 day clinical follow-up of STEMI patients in normal reactivity group and high reactivity group was not significantly different?P>0.05?.The results of intestinal microflora analysis showed that 52 fecal samples had 417bp effective sequence in each sample,and obtained 975 operation classification units?OTU?after clustering.The dilution curve showed that Chao1 index and observed Species index were significantly higher in high reactivity group than the normal reactivity group?P<0.01?and reflected that the intestinal flora microbial diversity in high reactivity group was better than that of the normal reactivity group.LEfSe analysis showed that Bacillus and Alphaproteobacteria in high reaction group were significantly higher than that in normal response group,intestinal flora distribution was significantly difference in two groups.ConclusionsThis study illustrated the existence of individual differences in the effect of ticagrelor antiplatelet effect in acute STEMI patients.Some STEMI patients taking ticagrelor showed initial platelet inhibition delay phenomenon.It is the antiplatelet effect cannot quickly reached that the high platelet reactivity phenomenon of ticagrelor after treated STEMI patients.At the same time,we used 16S rDNA microbial diversity detection method to explore that the intestinal microbial diversity in high reactivity group is more than that the other group,which may be the intestinal flora changes cases the high platelet reactivity.