P2Y12 Inhibitor In Patients With Clopidogrel Low-response For DAPT Of Efficacy And Safety

Objective: By the method of evidence-based,explore P2Y12 inhibitor applied to DAPT therapy efficacy and safety of the patients with clopidogrel low-response,to provide the evidence of individualized antiplatelet therapy for such patients.Methods:Searching Pubmed,The Cochrane Library,CNKI,Wanfangdatabasefrom libraries up to December 2016 about the relevant literatures of P2Y12 inhibitor applied to patients with clopidogrel low-response.According to the inclusion criteria,extract data independently by two researchers,according to the requirements of 《 The Translation of Cochrane Handbook for Systematic Reviews of Interventions》,to evaluate publication bias,and use the Review Manager5.3 software to meta analysis the major cardiovascular events(Major adverse cardiac and cerebrovascular events,MACE/MACCE),bleeding events,adverse drug reactionsand inhibition of platelet aggregation rate of the patients with clopidogrel low-response after DAPT treatment.We also analysis the sensitivity,heterogeneity and publication bias.Results: A total of 1870 articles were retrieved,and 14 RCTs with 1828 patients were included eventually,9 RCTs contains double dose of clopidogrel interventions,7 RCTs were contains ticagrelor interventions.1)Compared with standard maintenance-dose of clopidogrel,double-dose clopidogrel has obviously decreased the incidence rate of MACE/MACCE(RR = 0.30;95% CI: 0.21,0.43;P <0.00001),reduce the risk of ST occurred(RR = 0.25;95% CI: 0.11,0.59;P = 0.001),decreased in patients with cardiac readmission rate(RR = 0.35;95% CI: 0.16,0.75;P = 0.007).Lead to more bleeding events(RR = 1.57;95% CI: 1.06,2.31;P = 0.02),with minor bleeding events increase in the number of statistically significant(RR = 1.53;95% CI: 1.01,2.30;P = 0.04).There has no obvious difference with the incidence of adverse drug reaction(RR = 3.04;95% CI: 0.49,18.90;P = 0.23).And in terms of reduced platelet aggregation rate,double-dose clopidogrel effect more apparent(MD = 11.00;95% CI: 11.00,10.16;P < 0.00001). 2)Compared with standard maintenance-dose of clopidogrel,ticagrelor significantly reduced the incidence of MACE/MACCE(RR = 0.27;95% CI: 0.16,0.44;P < 0.00001),decreased the incidence rate of recurrence of angina(RR = 0.32;95% CI: 0.13,0.80;P = 0.01).For ticagrelor did not cause more bleeding events(RR = 0.34;95% CI: 0.04,3.18;P = 0.34),but increased the minor bleeding events(RR = 2.13;95% CI: 1.04,4.35;P = 0.04).In terms of adverse drug reactions,for ticagrelor lead to more difficulty breathing events(RR = 3.78;95% CI: 1.28,11.14;P = 0.02).Has obvious inhibitory effect on platelet aggregation rate(MD = 13.60;95% CI: 13.60,11.63;P < 0.00001).3)Double-dose clopidogrel compared with ticagrelor,for MACE/MACCE risk,there has no obvious difference(RR = 1.68;95% CI: 0.78,3.66;P = 0.19).But for ticagrelor are more likely to lead to bleeding events(RR = 0.52;95% CI: 0.27,1.00;P = 0.05).And ticagrelor have a higher chance of breathing difficulties(RR = 0.18;95% CI: 0.03,0.98;P = 0.05).Conclusion:1)Double-dose clopidogrel and ticagrelor both can significantly reduce the chance of MACE/MACCE in patients with clopidogrel low-response accept DAPT treatments after PCI,and the two interventions in reducing MACE/MACCE no difference;2)Double-dose clopidogrel and ticagrelor both can lead to more bleeding events,bleeding events with no difference between the standard maintenance-dose clopidogrel,but higher incidence of minor bleeding events,and ticagrelor bleeding events occurred more than double-dose clopidogrel;3)Compared ticagrelor with standard maintenance-dose clopidogrel and double-dose clopidogrel,adverse drug reactions of dyspnea happened higher risk;4)Double-dose clopidogrel and ticagrelor can reduce platelet aggregation rate,ticagrelor effect is more obvious;5)Early screening of the patients with clopidogrel low-response,and individualized drug use,is conducive to reducing the occurrence of clinical cardiovascular adverse events.