Efficacy Of Intensive-dose Atorvastatin In Preventing Contrast Induced Nephropathy In Elderly Patients With CHD Undergoing Percutaneous Coronary Intervention

Objective:The purpose of this study was to investigate the effect of intensive-dose atorvastatin on contrast induced nephropathy(CIN)after percutaneous coronary intervention(PCI)in elderly patients with coronary heart disease(CHD)through a prospective,randomized,controlled,multicenter study.To explore the possible mechanism of CIN,preventive mechanism and the drug safety.The preventive effect of CIN on patients with different risk stratification was further discussed.Methods:A total of 601 patients with coronary heart disease treated in PCI was enrolled from Tianjin Chest Hospital,Tianjin First Central Hospital,Tianjin Fourth Central Hospital,Tianjin TEDA Cardiovascular Hospital,The patients were randomly divided into the control group(n=300)and the intensive-dose atorvastatin group(n=301).The control group received routine atorvastatin treatment and hydration treatment;the intensive-dose atorvastatin group was given atorvasstatin(Pfizer Pharmaceuticals USA 20mg)40mg/d on the basis of conventional hydration treatment 1 day before and 3 days after PCI.Baseline data were collected for all enrolled patients.Patients were grouped according to the CIN scoring system of the center,low-risk group,medium-risk group,high-risk group and highest-risk group.The blood urea nitrogen(BUN),serum creatinine(SCr),estimate glomerular filtration rate(eGFR),interleukin-6(IL-6),hypersensitive C-reactive protein(hs-CRP),superoxide dismutase(SOD),tumor necrosis factor(TNF-?);CystatinC(CysC)and neutropil gelatinase-associated lipocalin(NGAL)before and after surgery were recorded.The incidence of postoperative CIN was recorded in both groups and in each subgroup.Observe and record the adverse reactions and adverse events of all patients during hospitalization.Results1.The baseline data of the two groups of patients had no statistical difference(P>0.05).There was no statistically significant difference in the preoperative baseline data between the intensive-dose atorvastatin group and the control group(P>0.05).2.The incidence of CIN was the primary endpoint(1)A total of 44 patients with CIN(7.3%)after PCI were recorded in the two groups,including 32 in the control group(10.7%)and 12 in the intensive-dose atorvastatin group(4.0%).There was a statistically significant difference in the incidence of CIN between the two groups(P<0.05).(2)Among the low-risk groups,12 patients(7.2%)in the control group and3 patients(1.8%)in the intensive-dose atorvastatin group had statistically significant differences(P<0.05).Among the medium-risk groups,14 patients(13.2%)in the control group and 5 patients(4.6%)in the intensive-dose atorvastatin group had statistically significant differences(P<0.05).Among the high-highest-risk groups,6patients(21.4%)in the control group and 4 patients(13.8%)in the intensive-dose atorvastatin group had no significant difference between the two groups(P>0.05).(3)Multivariate logistic regression analysis showed that intensive-dose atorvastatin(OR=0.388,95% CI=0.192~0.783,P=0.008)were protective factors for CIN,age(OR=1.061,95% CI=1.011~1.014,P= 0.016),acute myocardial infarction(OR =2.777,95% CI = 1.166 ~ 6.616,P = 0.021)can increase the risk of CIN.(4)Other subgroup analysis: Intensive atorvastatin treatment is more advantageous for the prevention of CIN in patients with non-acute myocardial infarction,diabetic patients,elderly male patients,and patients with better baseline renal function.3.Comparison of laboratory indicators:Comparison of laboratory biochemical indicators: There were no significant differences in preoperative test indicators among the subgroups.(1)Low-risk group: The levels of SCr,BUN,IL-6,hs-CRP,CysC,NGAL after operation in the intensive-dose atorvastatin group were lower than those in the control group(P < 0.05);the levels of eGFR and SOD were higher than those in the control group(P < 0.05);there was no significant difference in the levels of TNF-a after operation between the two groups(P > 0.05).The levels of SCr,BUN,IL-6,hs-CRP,SOD,TNF-a,CysC and NGAL in the two groups after PCI were higher than those before PCI(P < 0.05).The level of eGFR after operation in both groups was lower than that before operation(P < 0.05).(2)Medium-risk group:The levels of SCr,BUN,IL-6,hs-CRP,CysC,NGAL after operation in the intensive-dose atorvastatingroup were lower than those in the control group(P < 0.05);the levels of eGFR and SOD after PCI were higher than those in the control group(P < 0.05);there was no significant difference in the levels of TNF-a between the two groups(P > 0.05).The levels of SCR,BUN,IL-6,hs-CRP,SOD,TNF-a,CysC and NGAL in both groups were higher than those before operation(P < 0.05).The levels of eGFR after operation were lower than those before operation(P < 0.05).(3)High-highest-risk group: The levels of SCr,eGFR and TNF-a after operation were similar between the two groups(P > 0.05).The levels of BUN,IL-6,hs-CRP,CysC and NGAL in the intensive-dose atorvastatin group were lower than those in the control group(P <0.05),and the levels of SOD in the intensive-dose atorvastatin group were higher than those in the control group(P < 0.05).The levels of SCr,BUN,IL-6,hs-CRP,SOD,TNF-a,CysC,NGAL after operation were higher than those before operation(P <0.05).The level of eGFR was lower than that before operation(P < 0.05).4.Patients with CIN had significantly higher levels of CysC and NGAL at 24 h after surgery than those without CIN(P<0.05).Conclusion:1.Perioperative administration of short-term intensive atorvastatin treatment can effectively reduce the incidence of postoperative CIN in elderly patients undergoing elective PCI,and the prevention benefit is more significant in low-risk,intermediate-risk patients and diabetes.2.Contrast media may cause kidney damage and cause CIN through inflammation and oxidative stress as well as direct nephrotoxicity.3.Atorvastatin can reduce the levels of factors in the inflammatory response and oxidative stress,thereby exerting anti-inflammatory and anti-oxidative effects and preventing CIN.4.Intensive-dose atorvastatin is more effective than CIN in the conventional dose group and has good drug safety.