The Clinical Study Of Trimetazidine In The Modulation Of Energy Metabolism In Patients With Acute Myocardial Infarction

Objective: 1)Trimetazidine improves clinical outcomes in patients with chronic heart failure and stable coronary artery disease.However,no one study has comprehensively evaluated the efficacy of trimetazidine in patients with acute myocardial infarction(AMI);2)To evaluate the efficacy of trimetazidine in Type 2 Diabetes patients with AMI undergoing Percutaneous Coronary Intervention(PCI);3)To investigate combined efficacy and safety of trimetazidine and recombinant human brain natriuretic peptide(rhBNP)in Type 2 Diabetic patients with acute heart failure following AMI ?Methods: 1)We enrolled 401 Chinese patients.All patients were initially treated with normal therapy.In blinded fashion,patients were randomly divided into an experimental group and control group.The experimental group was given a loading dose of 60 mg trimetazidine,followed by 20 mg trimetazidine three times a day at admission.At 2 and 6days,we evaluated creatine kinase and its isoenzyme(CK and CK-MB),cardiac troponin I(cTnI),serum creatinine(Cr),serum urea,glucose,glutamic pyruvic transaminase(ALT),and glutamic oxaloacetictransaminase(AST).Additionally,by echocardiography,we assessed left ventricular ejection fraction(LVEF),left ventricular end-diastolic dimension(LVEDD),and cardiac output(CO);2)For this randomized study,we enrolled 173 AMI patients with Type 2 Diabetes undergoing PCI between January 1,2014,and January 1,2016.All patients received aspirin and ticagrelor upon admission and throughout their hospitalization.89 patients were included in experimental group,and 84 patients were included in control group.Patients in the experimental group were treated with a loading dose of 60 mg trimetazidine at admission,and 20 mg trimetazidine three times a day thereafter.The endpoints evaluated were CK,CK-MB,cTnI,Cr,serum urea,blood glucose,ALT,AST,left atrial dimension(LA),LVEF,LVEDD,and CO;3)A total of 122 Type 2 Diabetic patients with acute heart failure following AMI(KillipII ~ III)wererandomly divided into control group(n=41),rhBNP group(n=41),rhBNP combined with trimetazidine group(combined group,n=40).The three groups were initially treated with normal therapy.RhBNP group was additionally given 1.5?g/kg bolus in ten minutes,and followed 0.0075?g/(kg.min-1).The combined group was given rhBNP and trimetazidine on the basis of normal therapy,in which a loading dose of 60 mg trimetazidine was take orally,followed by 20 mg trimetazidine three times a day at admission.At 2 and 6 days,we evaluated creatine kinase(CK and CK-MB),cTnI,Cr,serum urea,glucose,ALT,ASTand NT-proBNP.Additionally,by echocardiography,we assessed LVEF,LA,LVEDD and CO.Results: 1)Compared with the control group,trimetazidine treatment significantly reduced CK and CK-MB on the second day in hospital(two P=0.022),and cTNI after six days in hospital(P=0.003).In addition,trimetazidine significantly reduced ALT and AST after 6 days(P=0.001,P=0.000,respectively),lowered glucose after 6 days(P=0.011),and increased LVEF after 10?14 days(P=0.039).There were no significant effects on Cr,serum urea,LVEDD or CO(all P>0.05);2)Compared with the control group,trimetazidine significantly reduced CK and CK-MB on the second day in hospital([797 ± 582] vs.[1092 ± 1114];[80 ± 60] vs.[105 ± 100];P=0.029,P=0.041,respectively),and cTNI after two and six days in hospital([13.5±12.7]vs.[19.8±19.2];[3.3 ± 3.2] vs.[4.8 ± 4.7];two-tailed P=0.012).In addition,trimetazidine significantly lowered liver enzymes(ALT,AST)at 6 days([29.0±11.6] vs.[42.4±24.5];[39.8±17.3]vs.[69.2±70.0];two-tailed P=0.000),lowered glucose after 6 days([6.80±2.12] vs.[7.59±2.24];P=0.019),and increased LVEF after ten to fourteen days([58.4±8.6] vs.[54.9±8.4];P=0.008).There were no significant effect on Cr and serum urea,([81.0±20.5] vs.[81.181.1±20.5];[6.5±2.6] vs.[7.6±17.7];P=0.988,P=0.569,respectively),nor on LA,LVEDD,and CO([36.3±4.5] vs.[37.0±4.1],P=0.264;[52.0±4.9] vs.[53.1±4.6],P=0.128;[5.4±0.9] vs.[5.4±0.9],P=0.929,respectively);3)Though rhBNP or trimetazidine combined with rhBNP significantly reduced CK and CK-MB than those in the control group on the second day in hospital(P<0.05),cTNI and NT-proBNP after two and six days(P < 0.05),and ALT and AST after 6 days(P < 0.05),they in the combined group were markedly improved than those in rhBNP group(P < 0.05).In addition,trimetazidine combined with rhBNP obviously reduced Cr,serum ure and glucose after 6 days(P < 0.05).LVEF in the rhBNP group and combined group was increased than that in the control group after 10?14 days(P<0.05),however,it in the combined group was significantly improved than those in other two groups(P<0.05).Trimetazidine combined with rhBNP increase CO(P < 0.05),while there were nosignificant effects on LA or LVEDD(all P > 0.05).There was not other serious side effects in three groups.Conclusions: 1)Among patients with AMI,trimetazidine reduces serum myocardial enzyme,lowers ALT and AST,moderates glucose,and improves left ventricular ejection fraction;2)Among Type 2 Diabetic patients with AMI undergoing PCI,trimetazidine significantly reduces serum myocardial enzyme,improves liver function,adjusts blood glucose and improves cardiac function;3)Among Type 2 Diabetic patients with acute heart failure following acute AMI,trimetazidine combined with rhBNP significantly reduces routine enzymatic and nonenzymatic biomarkers,improves left ventricular ejection fraction and cardiac output,lowers blood glucose and improves liver and kidney function.