The Effect Of Ticagrelor On Contrast Induced Nephropathy In Unstable Angina Patient Undergoing Percutaneous Coronary Intervention

Objective:This study was aimed to observe the effect of ticagrelor or colpidogrel on contrast-induced nephropathy(CIN)in unstable angina patients undergoing percutaneous intervention.Methods:This study was a randomized,paralleled,controlled trial.From January 2016 to January 2017,patients with unstable angine scheduled for percutaneous coronary intervention in the Cardiology Department of the second hospital of Hebei medical university were enrolled.Inclusion criteria: 1)age 18 or older;2)The diagnostic criteria of UA;3)Family members of patients had signed surgical informed consent.Exclusion criteria: All eligible patients didn't suffer from diseases as follows: 1)Cardiogenic shock;2)acute ST-segment elevated myocardial infarction or non-ST-segment elevated myocardial infarction requiring primary PCI;3)Allergic to ticagrelor and colpidogrel or contrast medium;4)uremia,renal failure receiving dialysis,previous contrast media exposure within 1 week and administration of nephrotoxic drugs,including N-acetylcysteine,metformin,within 48 h before the procedure;5)with Severe trauma,hemorrhagic disease,malignant tumor;6)left ventricular ejection fraction(LVEF)<30% or New York Heart Association(NYHA)IV class;7)Pregnant or lactating women;8)Informed consent was not signed by the patients or their relatives;Eligible patients were randomly assigned to ticagrelor group,were given the loading dose of 180 mg and the maintenance dose of 90 mg/d with 2 times for one day,and the patients in colpidogrel group received the loading dose of 300 mg and the maintenance dose of 75 mg/d with 1 times for one day.Both patients wether continous taking ticagrelor or clopidogrel decided by their clinic doctor according their conditions until their discharge.Other medications including anticoagulants,antiplatelet drug,statins,ACEI/ARB,?-blockers,CCBwere given according to the patient's condition.PCI was performed by the radial or ulnar path and totally met the success criteria of PCI.Non-ionic contrast medium(CM,Iodixanol,320 mg I/ml)was used in PCI.All patients received an intravenous infusion of 0.9 % saline at a rate of 1 m L/kg/h(0.5 m L/kg/h for patients with LVEF <40 %)at least 6 h before and 12 h after elective coronary procedure.The levels of Serum Creatinine(SCr)and cystatin C(Cys C)were measured on admission and at 24 h,48h,72 h after PCI.Estimated glomerular filtration rate(e GFR)and incidence of CIN were calculated.CKD staging was performed according to the estimated glomerular filtration level admitted to the hospital,the changes of renal function and the incidence of CIN were compared between the two groupsResult: Of the 240 eligible patients enrolled,120 were randomly assigned to receive ticagrelor(73 male,average age 62.6±9.5years old)and 120 to colpidogrel(78 male,average age 64.2±8.0years old).1 BaselineThere were no significant differences between the two groups in baseline characteristics,including gender distribution,age,body mass index(BMI),previous history of hypertension,diabetes mellitus and hyperlipidemia,LVEF,renal function and so on(P>0.05).There were no significant difference in basic medications and GRACE score,CRUSADE score,hydration liquid volume,total CM consumption,result of coronary arteriography between the two groups(P>0.05).All patients received PCI.Hypotension(BP <90mm Hg)and malignant arrhythmia(ventricular tachycardia,fibrillation,fultter)happened in neither groups.2 Comparison of renal function parameters and the incidence of CIN.There were no differences in SCr,e GFR and Cys C between the two groups on admission.There was a rise in SCr,Cys C and decrease in e GFR after PCI,reaching their respective peak 48 h after PCI.The level of SCr and Cys C in the Ticagrelor group was higher than that in the clopidogrel group and the level of e GFR was lower than that of the clopidogrel group,but the difference were not statistically significant(P all > 0.05).There were no significant differences in SCr,e GFR and Cys C between the two groups(P all>0.05)at 72 h and compared with baseline respectively(P all>0.05).There were 8 patients of the ticagrelor group and 5 patients of the colpidogrel group developed CIN.There was no statistically significant difference of CIN incidence between the two groups(6.7%&4.2%,P=0.39).No one received dialysis due to CIN in the two groups.3 Comparison of SCr,e GFR,Cys C and CIN in Different Renal Function PatientsThere was no significant difference in SCr,e GFR and Cys C between baseline and 48 h after PCI in patients with normal renal function and mild renal insufficiency(P>0.05).In patients with moderate renal insufficiency,the levels of SCr and Cys C were increased in the ticagrelor group at 48 h after PCI,and higher than that of clopidogrel group,the difference was statistically significant(98.5±10.5 vs.89.5±9.7,P=0.033;2.43±0.7 vs.1.94±0.4,P=0.038).The level of e GFR was lower than that of clopidogrel(46.7±6.1 vs.52.3±7.4,P=0.046),the difference was also statistically.There was no significant difference in the incidence of CIN between the two groups with moderate renal insufficiency(23.1%vs.15.4%,P>0.05).4 The incidence of major adverse events(MACE)and drug-related adverse events(table 7)The incidence of MACE in the ticagrelor and clopidogrel group has no no significant difference(P=0.236).Among the drug-related adverse events,6 patients in the ticagrelor group had dyspnea,and patients in the clopidogrel group had no dyspnea,but the patients with dyspnea were tolerated and no patients were discontinued.There were 7 patients in the ticagrelor group and 2 patients in the clopidogrel group develop gingival bleeding,and the difference was not statistically significant(P>0.05).Two groups of patients were not intracranial hemorrhage,gastrointestinal bleeding.Conclusion:In all patients with UA who undergoing percutaneous coronary intervention,general incidence of CIN in ticagrelor group and ciopidogrel group had no difference.However,increased incidence of CIN was observed in patients with moderate renal insufficiency in ticagrelor group.Prophylactic treatments should be helpful to these patients in the perioperative period.