The Improvement Of Ticagrelor For Clopidogrel Resistance On Patients With Acute Coronary Syndrome

Objective: With the improvement of our living standards,the incidenceof coronary heart disease is rising year by year,which was a serious threat toour health.Currently percutaneous coronary intervention(PCI) has become apreferred treatment option for patients suffering with acute coronarysyndrome(ACS).Therefore,dual antiplatelet therapy combining aspirin andclopidogrel was the standard care for patients who were undergoingPCI.However, even though dual antiplatelet therapy was given, acutethrombotic events still occured in2-3%patients.There have been concernsthat‘Clopidogrel Resistance (CR)’may lead to adverse cardiovascularoutcomes.Studies have shown that anti-platelet effect of clopidogrel isdose-dependent,the high dose of clopidogrel can inhibit platelet aggregationmore effectively.Ticagrelor, a reversible and direct-acting oral antagonist of the adenosinediphosphate receptor P2Y12, provides faster, greater, and more consistentP2Y12inhibition than clopidogrel.The Study of Platelet Inhibition and PatientOutcomes (PLATO) demonstrated treatment with ticagrelor,as compared withclopidogrel,significantly reduced the rate of death from vascular causes,myocardial infarction, or stroke without an increase in the rate of overall majorbleeding,in patients who have an acute cornary syndrome.However,there is noresearch to the improvement of ticagrelor for clopidogrel resistancecurrently.Therefore,we aim to investigate whether ticagrelor is associated withsignificant improved platelet activity after PCI in patients with clopidogrelresistance suffering with acute coronary syndrome and to evaluate its efficacyand safety in this study.Methods:Consecutive patients admitted to Department of Cardiology inthe General Hospital of Armed Police were enrolled between December2012 and January2014.They were patients with a diagonosis of NSTE-ACS whowere scheduled for PCI.Blood samples were obtained by venipuncture of theantecubital vein respectively between6-12h after the clopidogrel600mg.TheVASP phosphorylation analysis of blood collection was performed with BDFACSCalibur flow cytometer.According to the definition of High PlateletReactivity(PRI≥50%)accepted internationally which was correlated well withclinical prognosis of patients undergoing PCI,confirmed by several studiesand ROC curve analysis,76patients with high platelet reactivity(PRI≥50%)were included,and were randomized to clopidogrel75mg qd or clopidogrel150mg qd or ticagrelor90mg bid.The VASP assay was performed2days、7days and28days after PCI respectively. Meanwhile,the MACE,bleedingevents and adverse reactions were recorded.All patients received aspirin100mg qd.Results:1365consecutive patients admitted for PCI were prospectively screenedfor inclusion in this prospective,randomized,controlled study. A total of289patients were not included:114patients had clopidogrel therapy beforehospital,13patients had emergency PCI,4patients were suggested to receivesurgery CABG,50patients who did not reach the guideline of PCI,97patientshad a PRI less than50%after600-mg bolus of clopidogrel;4patients had Ccrless than25ml/min,7patients had NYHA IV.Therefore,76patients wereincluded and randomized to clopidogrel75mg qd group(n=26) or clopidogrel150mg qd group(n=25) or ticagrelor90mg bid group(n=25).2patients inclopidogrel75mg qd group,3patients in clopidogrel150mg qd group and2patients ticagrelor90mg bid group were drop-outs,which refused to test theplatelet function. Ultimately, there were24、22and23patients respectivelyfinished the whole study.2After28days antiplatelet treatment,the PRI decreased in three groups,meanwhile,it was significantly lower in patients receiving ticagrelor90mg bidgroup compared with other two groups.The PRI of clopidogrel75mg qdgroup,clopidogrel150mg qd group,ticagrelor90mg bid group were52.1%± 11.2，45.5%±9.7，22.4%±9.4,respectively(P＜0.001).After pairwisecomparison they all have statistic difference(P=0.03，P＜0.001，P＜0.001).3After28days antiplatelet treatment, the compliance rate of PRI ofclopidogrel75mg qd group,clopidogrel150mg qd group,ticagrelor90mg bidgroup were45.8%,68.2%,100%,respectively(P＜0.001).After pairwisecomparison clopidogrel75mg qd group and clopidogrel150mg qd group haveno statistic difference(P=0.1＞0.0125).Ticagrelor90mg bid group has statisticdifference compared with other two groups(P＜0.001,P=0.003).4During28days follow-up,2cardiovascular adverse events and2minor bleeding in clopidogrel75mg qd group;1cardiovascular adverse eventsand2minor bleeding in clopidogrel150mg qd group;4minor bleeding inticagrelor90mg bid group,not resulting in a statistically difference(MACE:P=0.4;minor bleeding:P=0.6),with no major bleedings recorded.Conclusions:1We found that routine maintentace dose ticagrelor and high maintentacedose clopidogrel can obviously suppress platelet reactivity by VASPphosphorylation analysis compared with routine maintentace doseclopidogrel,and routine maintentace dose ticagrelor was more significantiy.2There is a tendency that routine maintentace dose ticagrelor and highmaintentace dose clopidogrel can reduce MACE in ACS patients withclopidogrel resistance.3Routine maintentace dose ticagrelor and high maintentace doseclopidogrel did not increase bleeding events.