Protective Effects Of Alprostadil On Renal Function In Non-ST Segment Elevation Myocardial Infarction Patients With Renal Insufficiency Undergoing Percutaneous Coronary Intervention

Objective: The aim of the trial was to evaluate the protective effects of alprostadil on renal function in Non-ST Segment Elevation Myocardial Infarction(NSTEMI)patients with renal insufficiency undergoing percutaneous coronary intervention(PCI).Methods: This was a prospective randomized controlled trial.From December 2014 to December 2015,all consecutive NSTEMI patients with renal dysfunction in our cardiology department were enrolled.Eligible patients were randomly assigned to receiving alprostadil(PGE group,PGE)or placebo(control group,CON).60 patients were assigned to the two groups respectively.Inclusion criteria: 1)The diagnostic criteria of NSTEMI;2)The diagnostic criteria of stage 3 chronic renal disease,that is GFR<60ml·min-1·1.73m-2;3)Family members of patients had signed surgical informed consent.Exclusion criteria: All eligible patients didn’t suffer from diseases as follows: 1)Patients with ST-segment elevation myocardial infarction;2)Allergic to alprostadil,anesthetic or contrast medium;3)Cardiogenic shock required intra-aortic balloon pump(IABP)support;4)patients with symptomatic hypotension(SBP≤90mmHg);5)Chronic heart failure,NYHA class Ⅳ;6)Severe hepatic insufficiency;7)glaucoma;8)Severe trauma and other Anticoagulant or antiplatelet contraindications;9)Use of nephrotoxic drugs,including N-acetyl cysteine(NAC),VC/VE within one week;10)Severe anemia;11)Pregnant or lactating women;12)Informed consent was not signed by the patients or their relatives;13)Other conditions not suitable to primary PCI or alprostadil.Patients in PGE group were given alprostadil 10 ug twice a day from the day on admission until the 7th day after PCI besides sodium chloride injection.Sodium chloride injection was started 3h before PCI at a rate of 1.0ml/(kg*h)(0.5 ml/(kg*h)should LVEF of the patient was less than 40%)until 6h after PCI in the two groups.Other medications including anticoagulants,antiplatelet drug,statins,ACEI/ARB,βblockers were 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 low-osmolar contrast medium(CM,Ultravist,370 mg I/ml)was used in PCI.The levels of Serum Creatinine(SCr)and cystatin C(CysC)measured on admission and at hour 24,48,72,1 week and 1 month after PCI.Estimated glomerular filtration rate(eGFR)was calculated.All data were analyzed with SPSS 23.0.P < 0.05(2-tailed)was considered statistically significant.Results: Of the 120 eligible patients enrolled,60 were randomly assigned to receive alprostadil(PGE group,24 male,average age 66.5±7.4 years old)and 60 to placebo(CON group,24 male,average age 66.1±7.0 years 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 dislipidemia,basic heart rate,diastolic blood pressure,systolic blood pressure,random blood glucose,plasma BNP,cardiac markers,LVEF and so on(P>0.05).2 PCI resultsAll patients received PCI.There were no significant difference in hydration liquid volume,total CM consumption between the two groups(P>0.05).Hypotension(BP <90mmHg)and malignant arrhythmia(ventricular tachycardia,fibrillation,fultter)happened in neither groups.3 Comparison of renal function parametersThere were no differences in SCr,eGFR and CysC between the two groups on admission.There was a rise in SCr,CysC and decrease in eGFR after PCI,reaching their respective peak 48 h after PCI.There was no significant difference between the two groups in SCr and eGFR 24 h after PCI.There was a significant difference in CysC 24 h after PCI(2.04±0.38mg/L vs.2.20±0.39mg/L,P=0.025).There was significant difference in each of the three parameters between the two groups 48 h after PCI(SCr: 118.9 ±14.7μmol/L vs.125.8±13.9μmol /L,P=0.009;eGFR: 42.7±6.5ml·min-1·1.73 m-2 vs.39.8±5.3ml·min-1·1.73 m-2,P=0.012;CysC: 2.20±0.37 mg/L vs.2.35±0.38mg/L,P=0.038).No signicifant difference was observed in SCr,eGFR and CysC 72 h after PCI,but there was detectible difference compared with baseline(P<0.05).There were no significant differences in SCr,eGFR and CysC between the two groups and compared with baseline respectively 1 week after PCI.4 Incidence of CIN of the two groupsThere were 6 patients of the PGE group and 15 patients of the CON group developed CIN.Incidence of CIN was 10% and 25% in PGE and CON group respectively.There was statistically significant difference of CIN incidence between the two groups(P=0.031).No one received dialysis due to CIN in the two groups.5 Changes of renal function within 1 month and incidences of MACEsResults of the 1 month follow-up show that there was no significant differences of SCr,eGFR and Cys C between the two groups(SCr: 108.1±13.7μmol/L vs.109.6±14.9μmol/L,P=0.583;eGFR: 47.5 ±7.1ml·min-1·1.73 m-2 vs.46.8 ± 6.3ml·min-1·1.73 m-2,P=0.746;CysC: 1.72±0.36 mg/L vs.1.78±0.36mg/L,P=0.319)and compared with their baseline.MACEs happened in neither of the two groups.6 Safety evaluationNo hypotension occurred in patients receiving alprostadil.1 cases of phlebitis occurred but well tolerated and relieved by adjusting alprostadil dosage.No allergy,rash or gastrointestinal discomfort happened.Conclusion: Periprocedural intravenous infusion of alprostadil can alleviate renal impairment caused by CM,induce renal protection in NSTEMI patients with renal dysfunction undergoing PCI with no observable adverse effects.