| Objective:The relationship between antiplatelet drug-related genetic testing and thromboelastography-platelet mapping(TEG-PM)and the evaluation of antiplatelet drug efficacy in patients with intracranial aneurysms(IAs)treated with stents are analyzed.To investigate the value of antiplatelet drug-related genetic testing and TEG-PM in the antiplatelet therapy of patients with IAs after stenting.Methods:Based on 106 IAs patients treated with stent-assisted spring coil embolization and blood flow-directed devices from January 2019 to August 2022,all patients undergo antiplatelet drug-related genetic testing,and two clinical pharmacologists with at least five years of experience are asked to determine whether drug resistance is present.TEG-PM is performed in some patients after taking clopidogrel 75 mg/d and aspirin 100 mg/d for 5-7 days or a loading dose of 300 mg/d for one day each.The inhibition rate(AA%)reflects the efficacy of aspirin,and an AA% < 50% is considered to be inadequate for aspirin;the inhibition rate(ADP%)reflects the efficacy of clopidogrel,and an ADP% < 30% is considered to be inadequate for clopidogrel.Patients are divided into two groups,A and B.Group A(genetic test group)is adjusted according to the genetic test results related to aspirin and clopidogrel: patients without drug resistance are treated with the conventional drug regimen(regimen 1),i.e.,aspirin 100 mg/d and clopidogrel 75 mg/d;patients with aspirin resistance are treated with aspirin 300 mg/d and clopidogrel 75 mg/d after surgery(regimen 2);patients with clopidogrel genetic resistance are treated with aspirin 100 mg/d and Tegretol 90 mg/d bid after surgery(regimen 3).In group B(combined group),the dosing regimen is adjusted according to the results of the genetic test and TEG-PM test: regimen 1 for patients with effective TEG-PM inhibition and no genetic resistance to the drug;regimen 2 for patients with AA% <50% or aspirin genetic resistance;regimen 3 for patients with ADP% < 30% or clopidogrel genetic resistance after surgery.When TEG-PM results have an AA% <50% and an ADP% < 30%,medication changes should be given to patients with genetic resistance or low efficacy to prevent bleeding events due to overdose.Age,gender,and laboratory test data are collected for each patient.The occlusion of IAs,stent endothelial proliferation,and drug-related hemorrhagic and ischaemic complications are recorded during patient follow-up.Results:1.General dataA total of 123 IAs were treated in 106 patients,with an overall mean age of53.67 ± 6.66 years,the oldest being 71 years and the youngest 37 years,and 67patients(63.2%)were female.The patients were divided into groups A(41)and B(65).There was no statistical difference between the two groups regarding baseline data and IAs,and the type of stent used intraoperatively(P > 0.05).In group A,there were 26(63.4%),3(7.3%),and 12(29.3%)cases in regimens 1,2,and 3,respectively.There were 35(53.8%),2(3.1%),and 28(43.1%)cases in group B in regimens 1,2,and 3,respectively.The difference in the choice of drug regimen between the two groups was not statistically significant(P=0.326).2.Relationship between TEG-PM and antiplatelet drug genetic testing and evaluation of the efficacy of antiplatelet drugsTEG-PM and genetic testing results in 65 patients showed only 2 cases of genetic resistance to aspirin compared with 16 cases of AA% < 50% on TEG-PM and20 cases of genetic resistance to clopidogrel compared with 27 cases of ADP% < 30%on TEG-PM.Cohen`s kappa coefficients were used to analyze the concordance between the TEG-PM and genotype assessment tests.They showed that poor concordance between the two in assessing aspirin efficacy(Cohen`s kappa = 0.177,95% CI =-0.041-0.395,P = 0.012)and fair concordance between the two in assessing clopidogrel efficacy(Cohen`s kappa = 0.704,95% CI = 0.530-0.878,P < 0.001).3.Complications related to antiplatelet therapyTwo patients in Group A developed ischaemic complications at 3.6 and 1.6months after dosing,respectively,and were treated with antiplatelet therapy using regimen one;no ischaemic events occurred in Group B.Two patients in each of group A developed bleeding complications at 1.2 and 4.3 months after dosing,and were treated using regimen 3 and 2,respectively;four patients in group B developed hemorrhagic complications1.6,2.2,3.4 and 5.5 months after medication,respectively,and were treated with regimen 1,1,3 and 2,respectively.The difference in the incidence of complications related to antiplatelet therapy between the two groups was not statistically significant(P = 0.287;P = 0.782).4.IAs occlusion and stent intimal hyperplasiaAt one month postoperatively,41 and 65 patients in groups A and B were followed up,and there was no recurrence of IAs.18(43.9%)and 34(52.3%)patients had improved IAs occlusion compared with the previous condition,and 16(39.0%)and 22(33.8%)patients had complete IAs occlusion,respectively.31(75.6%)and 51(78.5%)patients had endothelial hyperplasia,and 2(4.9%)patients in group A had clinically significant endothelial hyperplasia.The two groups had no statistically significant difference(P > 0.05).41 and 64 patients in each of groups A and B were followed up at three months after surgery,and there was no recurrence of IAs.3(7.3%),12(18.8%)patients had improved IAs occlusion compared with the previous condition,and 25(61.0%)and 36(56.3%)patients had complete IAs occlusion.In both groups,intimal hyperplasia progressed compared with before,occurring in 38(92.7%)and 61(95.3%),respectively.There was no statistically significant difference between the two groups in terms of aneurysm occlusion and stent intimal hyperplasia(P > 0.05).41 and 61 patients in groups A and B were followed up at six months after surgery,and 33(80.5%)and 54(88.5%)patients had complete occlusion of IAs.All patients in group B had improved IAs occlusion compared to the previous,and the total IAs occlusion rate reached 85.3%.All patients in group A showed intimal hyperplasia and no new clinically significant intimal hyperplasia,while two patients(3.3%)in group B did not develop intimal hyperplasia.There was no statistically significant difference between the two groups in the grading of endothelial hyperplasia and the rate of aneurysm occlusion(P > 0.05).The NIH% at six months postoperatively was 0.94(0.93,0.96)and 0.95(0.94,0.96)in groups A and B,respectively,with a slightly higher overall intimal hyperplasia in group A than in group B.The difference between the two groups was statistically significant(P =0.034).Conclusions:1.TEG-PM can cover the antiplatelet drug-related gene assay evaluation for antiplatelet drug-gene resistance.The antiplatelet therapeutic efficacy of TEG-PM response is more comprehensive than that of antiplatelet drug-related gene assay.2.TEG-PM testing is a basic guide to antiplatelet aggregation treatment after intracranial aneurysm stenting,and antiplatelet drug-related genetic testing can be an essential complement to the testing of the cause of insufficient platelet inhibition.3.TEG-PM AA% < 50% and ADP% < 30% as cut-off values for determining the efficacy of aspirin and clopidogrel,respectively,is clinically feasible for guiding and adjusting antiplatelet aggregation therapy. |
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