| Antiplatelet therapy post-percutaneous coronary intervention(PCI)is the main tragedy to antithrombosis.Clopidogrel resistance affect the antithrombosis efficiency.Main cardiovascular cerebrovascular events and bleeding events are the main problem in antiplatelet therapy.Clopidogrel and ticagrelor are the most used anti platelet drugs.How to screening the target people and modulate the antiplatelet dose,more clinical research need to be carried out.CYP2C19 alleles controls the clopidogrel metabolism and induce clopidogrel resistance.To choose antiplatelet drug and dose based on CYP2C19 mutation,we carried out the present research.Part 1.Retrospective study to observe the prognosis relationship of CYP2C19 gene polymorphism and clopidogrel resistance in post-PCI patientsObjectives: To evaluate the prognosis relationship of CYP2C19 gene polymorphism and clopidogrel resistance in post-PCI patients and to be the basis of antiplatelet selection by CYP2C19 gene polymorphism.Methods: 536 patients diagnosed as acute coronary syndrome and PCI with CYP2C19 mutation and platelet inhibition rate were selected in Shenyang Fourth People’s Hospital from Jan.2015 to Dec.2017 and divided into three groups by CYP2C19 gene mutation.The prognosis relation of CYP2C19 gene polymorphism and clopidogrel resistance was observed.The relative factors with MACCE and survival was analyzed.Results: 1.In 536 patients post-PCI,14.74%,37.87% and 47.39% in poor,intermediate and rapid metabolism distribution,the platelet inhibition rate was different(P<0.05),the rate of clopidogrel resistance was different(P<0.05);2.In the three metabolism groups,five years survival was the same,also in clopidogrel resistance and non-resistance groups;3.The five years survival in clopidogrel resistance and nonresistance groups by three metabolism groups was the same.4.Clopidogrel resistance was post-PCI MACCE risk factor,CYP2C19 was not,clopidogrel resistance was the independent risk factors.Conclusions: 1.The platelet inhibition rate was low in poor and intermediate metabolizer,clopidogrel resistance rate was high,especially in poor metabolizer;2.There was not any relationship between CYP2C19 mutation and clopidogrel resistance in long survival;3.There was no relationship between CYP2C19 mutation and MACCE risk,the MACCE risk was related with clopidogrel resistance.Part 2.Observe the prognosis relationship of CYP2C19 gene polymorphism and ticagrelor in post-PCI patients in LiaoningObjectives: To evaluate the prognosis relationship of CYP2C19 gene polymorphism and ticagrelor in post-PCI patients in Liaoning in post-PCI patients and to evaluate the therapy effect and safety of ticagrelor.Methods: 309 patients diagnosed as acute coronary syndrome and PCI with CYP2C19 mutation and platelet inhibition rate were selected in Shenyang Fourth People’s Hospital from Jan.2018 to Dec.2019 and divided into clopidogrel group and ticagrelor group.The prognosis relation of CYP2C19 gene polymorphism and ticagrelor was observed.The relative factors with MACCE and survival was analyzed.Results: 1.The platelet inhibition rate in ticagrelor group was higher than in clopidogrel group.In clopidogrel group,the platelet inhibition rate in rapid metabolizer was higher than in poor and intermediate metabolizer.In ticagrelor group,the platelet inhibition rate in the three metabolizers was the same;2.In the three metabolizers,the platelet inhibition rate in ticagrelor group was higher than in clopidogrel group;3.The two years survival in ticagrelor and clopidogrel group was the same;4.In ticagrelor and clopidogrel groups,the three metabolized had the same 24 months survival;5.MACCE in ticagrelor and clopidogrel groups was the same.6.Total bleeding events in clopidogrel group was lower than in ticagrelor group;7.Age(>75y),gender(male),high BMI(BMI≥24),diabetes mellitus,smoking,number of stents(≥3),and multi vessel disease(≥2)were risk factors for MACCE.CYP2C19 gene polymorphism was not a risk factor for MACCE after PCI.CYP2C19 gene mutation did not increase the risk of MACCE;8.Age(>75y),gender(female),low BMI(<18.5),middle and high risk of Crusade score and antiplatelet therapy were related risk factors of bleeding after PCI,while middle and high risk of Crusade score were independent risk factors of bleeding after PCI.Conclusions: 1.The antiplatelet efficiency of ticagrelor was higher than clopidogrel.CYP2C19 did not affect the 24 months survival;2.MACCE in ticagrelor and clopidogrel groups were the same and did not raise the MACCE risk;3.The bleeding risk of ticagrelor was higher than that of clopidogrel,and the bleeding severity was statistically different.In patients with moderate and high-risk Crusade score,antiplatelet therapy after PCI increased the risk of bleeding;4.CYP2C19 gene polymorphism was not associated with MACCE and bleeding events;5.Female,low weight and old age are the related risk factors of bleeding events after PCI,and middle and high risk of Crusade score are the independent risk factors of bleeding events after PCI.Part 3.A case-control study to observe the ticagrelor de-escalation antiplatelet in intermediate-poor metabolizer CYP2C19 mutation patients with medium-high bleeding risk post-PCIObjectives: To evaluate the prognosis and adverse reaction of the ticagrelor deescalation antiplatelet in intermediate-poor metabolizer CYP2C19 mutation patients with medium-high bleeding risk post-PCI,objective to provide clinical evidence for the initiation of antiplatelet therapy after PCI in Chinese patients with high risk of bleeding and thrombosis.Methods: 178 patients diagnosed as acute coronary syndrome and PCI with CYP2C19 mutation were selected in Shenyang Fourth People’s Hospital from Jun.2019 to Feb.2020 and divided into ticagrelor 90 mg group and ticagrelor 60 mg group.The prognosis relation of CYP2C19 gene polymorphism and ticagrelor was observed.The relative factors with MACCE,bleeding risk,dyspnea and survival was analyzed.Results: 1.The platelet inhibition rate in ticagrelor 90 mg group and ticagrelor60 mg group was(78.33±12.99)% and(56.49±16.32)%(P<0.0001);2.MACCE in ticagrelor 90 mg group and ticagrelor 60 mg group was the same;3.KM curve showed that MACCE risk in ticagrelor 90 mg group was higher than in ticagrelor 60 mg group;4.Compared with ticagrelor 90 mg,ticagrelor 60 mg decreased the total bleeding events rate;5.KM curve showed that total bleeding risk in ticagrelor 90 mg group was higher than in ticagrelor 60 mg group.Severe bleeding in 90 mg was higher than in 60 mg group;6.Dyspnea rate in ticagrelor 60 mg group was lower than in 90 mg group.7.The 12 months survival in ticagrelor 90 mg group and ticagrelor 60 mg group was the same;8.Age(>75y),gender(male),high BMI(BMI≥24),number of stents(≥3),multi vessel disease(≥2)and smoking were related risk factors of MACCE,but they were not independent risk factors of MACCE;9.Moderate and high risk of fracture score are independent risk factors for bleeding after PCI,and CYP2C19 gene mutation is not an independent risk factor for bleeding events.Conclusions: 1.The platelet inhibition rate was satisfied when ticagrelor deescalated from 90 mg to 60 mg,and the prognosis was not affected,the MACCE was the same,total bleeding event rate was decreased,severe bleeding event was decreased.Dyspnea events was decreased also;2.Ticagrelor 90 mg.bid.po/d,ticagrelor60 mg.bid.po/d and CYP2C19 gene medium and slow metabolism were not independent risk factors of MACCE and bleeding events after PCI,while CRUSADE score medium and high risk were independent risk factors of bleeding after PCI.3.In our country,the patients with high risk of bleeding and thrombosis should take antithrombotic treatment after PCI,which has the same curative effect and less side effects compared with non reduction treatment,and is conducive to clinical promotion in the future. |
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