Effect Of Hepatitis B Virus(HBV)Infection On The Efficacy Of DAPT In Patients Undergoing Coronary Stent Implantation

Objectives:The purpose of this study was to evaluate the effect of hepatitis B virus(HBV)infection on the efficacy of dual anti-platelet therapy(DAPT)in patients undergoing percutaneous coronary intervention(PCI).Methods:A total of 1742 subjects who had received coronary stent implantation and taken daily aspirin 100mg daily clopidogrel 75mg≥5 days were prospectively and consecutively recruited,and the serologic identification for HBV were tested during their hospitalization.We defined HBsAg-positive patients as HBV carriers group and HBsAg-negative patients as non-HBV carriers group respectively.Platelet aggregation in response to lmmol/L arachidonic acid(PLAA)and 5pmol/L adenosine diphosphate(PLADP)were determined for each subject by light transmittance aggregometry(LTA).The single nucleotide polymorphism might influence the metabolism of clopidogrel was detected at the same time.Both groups were followed up by telephone or outpatient service at the first months,sixth months and one year after PCI.One year related clinical events including cardiac death,nonfatal myocardial infarction,unstable angina,stroke,target vessel revascularization(TVR),as well as safety events including major and minor bleeding defined by TIMI bleeding were recorded.Results:Among the recruited subjects,105 HBsAg-positive patients and 1588 HBsAg-negative patients were successfully followed up.The aspartate aminotransferase(AST)and platelet counts between two groups were significantly different[(73.4±113.4 vs.53.1±92.5,P=0.036)and(180±60.2 vs.193.4±62.5,P=0.035)],while the other clinical data,the characteristics of coronary angiography and coronary intervention were similar between the two groups(P>0.05).The level of PLADP was higher in the HBsAg-positive group than that in the HBsAg-negative group[(37.56± 15.55)%vs.(30.02±14.16)%,p<0.01],while the levels of PLAA were similar between the two groups[(5.05±7.95)%vs.(4.24±16.17)%,p=0.215].We defined PLADP>40%as clopidogrel low response(CLR),PLAA>20%as aspirin resistance(AR).As a result,HBV carriers presented a higher incidence of CLR than that of non-HBV carriers(46.7%vs.22.3%,P<0.01),but the incidence of AR were similar between the two groups(1.9%vs.1.1%,P=0.758);Cytochrome 450 2C19(CYP2C19)genotype status were predictors for the response of clopidogrel.Extensive and intermediate metabolizer predicted lower risk of CLR(OR:0.29;95%CI:0.20-0.41,P<0.01&OR:0.69;95%CI:0.58-0.81,P<0.01),while poor metabolizer predicted higher risk of CLR(OR:1.38;95%CI:1.25-1.53,P<0.01).At the 1 year’s follow-up,although the incidences of cardiovascular death(0.95%vs.1.0%,P=0.652),myocardial infarction(2.9%vs.1.1%,P=0.240),unstable angina(9.5%vs.5.2%,P=0.056),stroke(1.9%vs.0.9%,P=0.261)and TVR(4.8%vs.4.4%,P=0.941)showed no statistical significance between the two groups,the total adverse clinical events were significantly increased in HBV carriers compared with the non-HBV carriers(p=0.028).The patients with CLR predicted higher risk of adverse clinical events(OR:1.40;95%CI:1.10-1.78,P<0.01).But the risks of bleeding were similar between the two groups(16.2%vs.18.8,P=0.502).Conclusion:HBV carriers exhibited significantly higher incidence of clopidogrel low response with higher risk of adverse clinical outcomes after PCI.