Trimetazidine (TMZ) is a metabolic agent with significant anti-ischemic properties. By inhibiting the terminal enzyme in the β-oxidation pathway, it shifts the energy substrate metabolism, enhancing glucose metabolism. Thus, it maintains the required energy production with less oxygen consumption, an effect necessary in cases of myocardi. Trimetazidine was recently reaccredited as add-on therapy for symptomatic treatment in patients with stable angina, not adequately controlled or intolerant to first-line therapy. Trimetazidine was included in the European Society of Cardioloy 2013 guidelines for the management of stable coronary artery disease. Although TMZ has been used in cardiology for >40 years, only a few studies have assessed its effects in patients with acute ischemic conditions. This review summarizes the current literature regarding the addition of TMZ in patients with acute ischemic conditions (acute myocardial infarction, ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting). There is growing evidence from recent studies that the addition of TMZ in patients with such conditions is beneficial in terms of myocardial damage and major cardiac events as well as decreasing reperfusion injury and contrast-induced nephropathy.
TsioufisKAndrikopoulosGManolisA. Trimetazidine and cardioprotection: facts and perspectives. Angiology. 2015;663(3):204–10.
2.
VitaleCSpoletiniIMalorniW. Efficacy of trimetazidine on functional capacity in symptomatic patients with stable exertional angina—The VASCO-angina study. Int J Cardiol. 2013;168(2):1078–81.
3.
DanchinNMarzilliMParkhomenkoARibeiroJP. Efficacy comparison of trimetazidine with therapeutic alternatives in stable angina pectoris: a network meta-analysis. Cardiology. 2011;120(2):59–72.
4.
SzwedHSadowskiZElikowskiW. Combination treatment in stable effort angina using trimetazidine and metoprolol: results of a randomized, double-blind, multicenter study (TRIMPOL II). TRIMetazidine in POLand. Eur Heart J. 2001;22(24):2267–74.
MontalescotGSechtemUAchenbachS. ESC guidelines on the management of stable coronary artery disease: the Task Force on the Management of Stable Coronary Artery Disease of the European Society of Cardiology. Eur Heart J. 2013;349(38):2949–3003.
7.
JacksonG. Combination therapy in angina: a review of combined hemodynamic treatment and the role for combined hemodynamic and cardiac metabolic agents. Int J Clin Pract. 2001;55(4):256–61.
8.
LiLZhaoXLuYHuangWWenW. Altered expression of pro- and anti-inflammatory cytokines is associated with reduced cardiac function in rats following coronary microembolization. Mol Cell Biochem. 2010;342(1-2):183–90.
9.
KantorPFLucienAKozakRLopaschukGD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2000;86(5):580–8.
10.
StanleyWCMarzilliM. Metabolic therapy in the treatment of ischaemic heart disease: the pharmacology of trimetazidine. Fundam Clin Pharmacol. 2003;17(2):133–45.
11.
RagassoGPiattiPMMontiL. Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy. Am Heart J. 2003;146(5):E18.
12.
Di NapoliP. Anti-ischemic cardioprotection with trimetazidine. Heart Metab. 2008;41:25–9.
13.
ShehataM. Cardioprotective effects of oral trimetazidine in diabetic patients with anterior wall myocardial infarction treated with thrombolysis. Cardiol Res. 2014;5(2):58–67.
14.
MarzilliM. Cardioprotective effects of trimetazidine: a review. Curr Med Res Opin. 2003;19(7):661–72.
15.
MacInnesAFairmanDABindingP. The antianginal agent trimetazidine does not exert its functional benefit via inhibition of mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2003;93(3):e26–32.
16.
StegPGGrollierGGallayP. LIST Study Group. A randomized double-blind trial of intravenous trimetazidine as adjunctive therapy to primary angioplasty for acute myocardial infarction. Int J Cardiol. 2001;77(2-3):263–73.
17.
DongXDHuDYJiaSQWangLYanSB. Clinical study of trimetazidine for myocardial protection in acute myocardial infarction[in Chinese]. Zhonghua Nei Ke Za Zhi. 2007;46(8):633–6.
18.
Di PasqualePLo VersoPBuccaV. Effects of trimetazidine administration before thrombolysis in patients with anterior myocardial infarction: short-term and long-term results. Cardiovasc Drugs Ther. 1999;13(5):423–8.
19.
DemirelliSKarakelleoğlu GündoğduF. The impact of trimetazidine treatment on left ventricular functions and plasma brain natriuretic peptide levels in patients with non-ST segment elevation myocardial infarction undergoing percutaneous coronary intervention. Korean Circ J. 2013;43(7):462–7.
20.
FoadKElmahmoudyABastawyIKhaledS. Effect of trimetazidine on myocardial salvage index in patients with acute ST segment elevation myocardial infarction undergoing primary PCI. Egyptian Heart J. 2013;65(3):181–9.
21.
The EMIP-FR Group. Effect of 48-h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy. A double-blind, placebo-controlled, randomized trial. European Myocardial Infarction Project-Free Radicals. Eur Heart J. 2000;21(18):1537–46.
22.
KimJSKimCHJeongMH. Effects of trimetazidine in patients with acute myocardial infarction: data from the Korean Acute Myocardial Infarction Registry. Clin Res Cardiol. 2013;102(12):915–22.
23.
OkabeEFujimakiRMurayamaMItoH. Possible mechanism responsible for mechanical dysfunction of ischemic myocardium: a role of oxygen free radicals. Jpn Circ J. 1989;53(9):1132–7.
24.
BolliRJeroudiMOPatelBS. Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. evidence that myocardial “stunning” is a manifestation of reperfusion injury. Circ Res. 1989;65(3):607–22.
25.
IoannidisJPKarvouniEKatritsisDG. Mortality risk conferred by small elevations of creatine kinase-MB isoenzyme after percutaneous coronary intervention. J Am Coll Cardiol. 2003;42(8):1406–11.
26.
Authors/Task Force members: The task force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35(37):2541–619.26
27.
BulkelyBHHutchinsGM. Myocardial consequences of coronary artery bypass graft surgery: the paradox of necrosis in areas of revascularization. Circulation. 1977;56(6):906–13.
28.
MartinsGFSiqueira FilhoAGSantosJB. Trimetazidina na injúria de isquemia e reperfusão em cirurgia de revascularização do miocárdio [in Portuguese]. Arq Bras Cardiol. 2011;97:209–16.
29.
FiqueiredoLGMartin-NetoJA. Proteina C-reativa elevada e intervenção coronária percutânea: causa ou efeito? [in Portuguese]. Rev Bras Cardiol Invas. 2000;14:7–9.
30.
Di NapoliPDi GiovanniPGaetaMATaccardiAABarsottiA. Trimetazidine and reduction in mortality and hospitalization in patients with ischemic dilated cardiomyopathy: a post hoc analysis of the Villa Pini D’Abruzzo Trimetazidine Trial. J Cardiovasc Pharmacol. 2007;50(5):585–9.
31.
FabianiJNPonzioOEmeritI. Cardioprotective effect of trimetazidine during coronary artery graft surgery. J Cardiovasc Surg (Torino). 1992;33(4):486–91.
32.
AussedatJRayAKayLVerdysMHarpeyCRossiA. Improvement of long-term preservation of isolated arrested rat heart: beneficial effect of the antiischemic agent trimetazidine. J Cardiovasc Pharmacol. 1993;21(1):128–35.
33.
El BananiHBernardMBaetzD. Changes in intracellular sodium and pH during ischaemia-reperfusion are attenuated by trimetazidine. Comparison between low- and zero-flow ischaemia. Cardiovasc Res. 2000;47(4):688–96.
34.
TünerirBColakOAlataşOBesoğulYKuralTAslanR. Measurement of troponin T to detect cardioprotective effect of trimetazidine during coronary artery bypass grafting. Ann Thorac Surg. 1999;68(6):2173–6.
35.
LopatinIUMDronovaEP. Clinical-pharmacoeconomic aspects of trimetazidine modified release use in patients with ischemic heart disease undergoing coronary artery bypass grafting. Kardiologiia. 2009;49(2):15–21.
36.
BanachMRyszJZasłonkaJ. The cardioprotective effect of trimetazidine in patients undergoing surgical revascularization. Russ Med J. 2005;13:1269–71.
37.
ZhangN. The effectiveness of preoperative trimetazidine on myocardial preservation in coronary artery bypass graft patients: a systematic review and meta-analysis. Cardiology. 2015;131(2):86–96.
38.
Sher-i-MurtazaMZubairMJalalA. Is there any benefit of preoperative oral trimetazidine in coronary artery bypass graft?J Pak Med Assoc. 2012;62(12):1271–6.
39.
VedrinneJMVedrinneCBompardDLehotJJBoisselJPChampsaurG. Myocardial protection during coronary artery bypass graft surgery: a randomized, double-blind, placebo-controlled study with trimetazidine. Anesth Analg. 1996;82(4):712–839.
40.
ThygesenKAlpertJSJaffeASSimoonsMLChaitmanBRWhiteHD. Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction. ESC Committee for Practice Guidelines (CPG). Third universal definition of myocardial infarction. Eur Heart J. 2012;33(20):2551–67.
41.
LinXMaAZhangW. Cardioprotective effects of atorvastatin plus trimetazidine in percutaneous coronary intervention. Pak J Med Sci. 2013;29(2):545–8.
42.
XuXHZhangWJZhouYJ. Effects of trimetazidine therapy on left ventricular function after percutaneous coronary intervention [in Chinese]. Zhonghua Xin Xue Guan Bing Za Zhi. 2013;41(3):205–9.
43.
LabrouAGiannoglouGZioutasDFragakisNKatsarisGLouridasG. Trimetazidine administration minimizes myocardial damage and improves left ventricular function after percutaneous coronary intervention. Am J Cardiovasc Drugs. 2007;7(2):143–50.
44.
ZhangY. Effect of trimetazidine in patients undergoing percutaneous coronary intervention: a meta-analysis. PLoS One. 2015;10(9):e0137775.
45.
BonelloLSbragiaPAmabileN. Protective effect of an acute oral loading dose of trimetazidine on myocardial injury following percutaneous coronary intervention. Heart. 2007;93(6):703–7.
46.
PolonskiL.DecI.WojnarRWilczekK. Trimetazidine limits the effects of myocardial ischaemia during percutaneous coronary angioplasty. Curr Med Res Opin. 2002;18(7):389–94.
47.
YilmazAErdemAKucukdurmazZ. Beneficial effects of preprocedural trimetazidine on periprocedural myocardial damage. HealthMED. 2013;7:751–7.
48.
KuralayFAltekinEYazlarASOnvuralBGoldeliO. Suppression of angioplasty-related inflammation by pre-procedural treatment with trimetazidine. Tohoku J Exp Med. 2006;208(3):203–12.
49.
XuXH. Effects of trimetazidine therapy on left ventricular function after percutaneous coronary intervention[in Chinese]. Zhonghua Xin Xue Guan Bing Za Zhi. 2013;41(3):205–9.
50.
MehranRNikolskyE. Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int Suppl. 2006;(100):S11–5.
AygenBCelikerHDogukanAIlhanN. The effects of trimetazidine on lipid peroxidation in patients with end-stage renal disease. Methods Find Exp Clin Pharmacol. 2008;30(10):757–60.
53.
GünalAICelikerHUstundagBAkpolatNDogukanAAkcicekF. The effect of oxidative stress inhibition with trimetazidine on the peritoneal alterations induced by hypertonic peritoneal dialysis solution. J Nephrol. 2003;16(2):225–30.
54.
SinghDChopraK. Effect of trimetazidine on renal ischemia/reperfusion injury in rats. Pharmacol Res. 2004;50(6):623–9.
55.
NadkarniGN. Trimetazidine decreases risk of contrast-induced nephropathy in patients with chronic kidney disease: a meta-analysis of randomized controlled trials. J Cardiovasc Pharmacol Ther. 2015;20(6):539–46.
56.
RahmanMMHaqueSSRokeyaB. Trimetazidine in the prevention of contrast induced nephropathy after coronary angiogram. Mymensingh Med J. 2012;21(2):292–9.
57.
OnbasiliAOYenicerigluYAgaogluP. Trimetazidine in the prevention of contrast-induced nephropathy after coronary procedures. Heart. 2007;93(6):698–702.
58.
LiuW. Trimetazidine prevention of contrast-induced nephropathy in coronary angiography. Am J Med Sci. 2015;350(5):398–402.
