The Lipid Profile Modification And Anti-oxidative Effect Of Atorvastatin Alone Or With Probucol In Patients With Acute Coronary Syndrome

Objectives:The aim of the present study was to compare the effect of atorvastatin and probucol combined with atorvastatin on the levels of serum oxidized low-density lipoprotein(ox-LDL)and paraoxonase-1 (PON1)activity in the early phase of acute coronary syndrome(ACS).Methods:A randomized,open study was performed on a total of 38 patients(including 27 males and 11 females,the average age was 63.7±8.9 years)with ACS.The patients were randomly assigned to an atorvastatin group(atorvastatin 10 mg/d,n=20)or a combined treatment group(atorvastatin 10 mg/d and probucol 1000mg/d,n=18).Serum total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C),triglyceride(TG),PON1 and ox-LDL were measured at baseline and after 4 weeks.Serum PON1 aryl esterase activities were assayed by phenyl acetate.The serum ox-LDL levels were determined by a commercially available ELISA kit.Adverse effects of drugs were monitored during the follow-up period.Results:1.After 4 weeks,LDL-C levels reduced by 15.4%(P＜0.05),HDL-C increased by 13.7%(P＜0.05)in the atorvastatin group.The serum TC,TG had declined tendency,but there were no statistical significance compared with the baseline.The atorvastatin combined with probucol produced a significant reduction in serum TC,LDL-C,HDL-C(-28.1%,-28.5%, -14.2%,respectively,P＜0.01)and TG(-23.3%,P＜0.05).TC,LDL-C,HDL -C were lower in the combined treatment group than in the atorvastatin group(P＜0.01)2.Serum PON1 activity increased significantly and ox-LDL levers declined significantly in both groups comparing with baseline after 4 weeks.In the atorvastatin group,PON1 activity increase from 210.5±53.9 to 230.5±58.9(+9.5%)KU/L(P＜0.01)and ox-LDL levels declined from 603.9±96.6 to 412.0±51.5 ug/L(P＜0.01).In the combined treatment group,PON1 increase from 216.6±47.6 to 244.7±53.8 KU/L(P＜0.01)and ox-LDL levels declined from 603.9±96.6 to 412.0±51.5 ug/L(P＜0.01). The increase of PON1 activity and decline of ox-LDL levels were more significant in the combined treatment group than in the atorvastatin group(P＜0.01).3.The serum levels of PON1 and ox-LDL had a significant negative correlation only before treatment(r=-0.669,P＜0.01)by Pearson correlation analysis.No relationship were observed between TC,TG,LDL-C,HDL-C and PON1 or ox-LDL.The changes of PON1 activity and ox-LDL levels did not correlate with the changes of serum lipids levels in either group studied.4.During the follow up period,no adverse reactions,such as hyper -sensitiveness,muscle haphalgesia,debilitation,and increasing of serum creatine kinase,had been observed.The QT interval and the corrected QT interval(QTc)did not prolonged after therapy(P＞0.05).Conclusion:1.The addition of probucol to atorvastatin produced a significant further reduction in serum TC,LDL-C in ACS patients.The two drugs may have a synergistic effect in lowing the cholesterol.2.The decrease of HDL-C in the combined treatment group indicated that atorvastatin could not offset the HDL-decreasing effect of probucol.3.Serum PON1 activity increased,ox-LDL leaves decreased in both atorvastatin group and combined treatment group.The changes of PON1 and ox-LDL were more significant in the combined treatment group. Atorvastatin combined with probucol may have stronger anti-oxidative effect.4.The anti-oxidative effect of atorvastatin and probucol was in dependant of lipids- regulating effect.5.Atorvastatin combined with probucol was safety and effective in ACS patients.