Does trimetazidine prevent myocardial injury after percutaneous coronary intervention?
Mario Marzilli About the author
Correspondence Cardio Thoracic Department, Division of Cardiology, University of Pisa, Via Paradisa, 256100 Pisa, Italy
Email marzilli@med.unipi.it
Original article
Bonello L et al. (2007) Protective effect of an acute oral loading dose of trimetazidine on myocardial injury following percutaneous coronary intervention. Heart 93: 703–707 PubMed
Practice point
Effective cardioprotection during PCI can be achieved with a single oral dose of trimetazidine, even in high-risk subgroups, but evidence of long-term benefit must be obtained before routine use of trimetazidine during PCI can be justified
Synopsis
Background
The anti-ischemic agent trimetazidine has been shown to reduce ischemia during percutaneous coronary intervention (PCI), but it is not known whether this agent prevents postprocedural myocardial necrosis.
Objective
The authors investigated whether an oral loading dose of trimetazidine, given before PCI, affects the incidence of postintervention myocardial injury.
Design
This was a prospective, open, randomized trial conducted at the University Hospital Nord, Marseille, France, from September 2003 to September 2005. Consecutive patients with stable angina pectoris who were scheduled to undergo PCI with single-vessel stenting were enrolled. Individuals with elevated cardiac troponin Ic (cTnI) before PCI, multivessel disease, contraindications for aspirin or clopidogrel, or previous treatment with trimetazidine, were excluded.
Intervention
Randomization took place after coronary angiography, and patients were assigned to receive 60 mg of oral trimetazidine 30 min before PCI or not to receive the study drug. PCI was performed through the femoral route, with an intravenous 100 IU/kg bolus of unfractionated heparin at the start of the procedure. All patients received clopidogrel in a 300 mg oral bolus the day before the procedure and at 75 mg/day for 1 month afterwards. Lifelong treatment with aspirin (160 mg/day) was also recommended. Blood samples for the assessment of cTnI were taken at baseline and at 6, 12, 18, and 24 h after PCI, and 12-lead electrocardiography was performed before intervention, and 1 h and 1 day afterwards.
Outcome measures
The primary end point was the peak level of cTnI. The total amount and the frequency of cTnI release were also measured as secondary end points.
Results
Of the 582 patients initially randomized, 316 were excluded because they underwent more than one balloon inflation during PCI. The final study population comprised 136 patients randomly allocated to trimetazidine therapy and 130 assigned to the control group. Patients receiving trimetazidine were at higher clinical and angiographic risk than controls (59 vs 23 patients had diabetes; mean BMI 27.2 vs 21.6 kg/m2; mean age 68 vs 53 years; Canadian Cardiovascular Society class 3 and 4 angina 47 vs 20 patients; AHA/ACC type B2 and C lesions 59 vs 30 patients; P <0.001 for all). Mean post-PCI cTnI level was significantly higher in the control group than the trimetazidine group for all time intervals (6 h = 4.2 vs 1.7 ng/ml; 12 h = 5.5 vs 2.3 ng/ml; 18 h = 9.0 vs 3.0 ng/ml; 24 h = 3.2 vs 1.0 ng/ml; P <0.001 for all). The area under the receiver operating characteristic curve for cTnI release after PCI was significantly greater for the control group than for the group receiving trimetazidine (P <0.05). There was, however, no difference between the two groups in the frequency of cTnI release. Trimetazidine was well tolerated with no serious adverse events reported.
Conclusion
A 60 mg oral loading dose of trimetazidine administered before PCI protects against postprocedure myocardial injury, as assessed by cTnI level.
Commentary
Myocardial damage can be caused during PCI by accumulation of atherosclerotic debris at the distal coronary bed, and by ischemia–reperfusion injury associated with balloon inflation–deflation. Even minimal myocardial damage is associated with impaired patient outcome, including an increased risk of mortality and of reinfarction during follow-up.1
Prevention or limitation of PCI-related myocardial damage involves resumption of normal oxidative metabolism and restoration of myocardial energy reserves. Partial inhibition of free fatty acid 
-oxidation by trimetazidine, a 3-ketoacyl coenzyme A thiolase blocker, switches energy substrate preference in the heart from fatty acid to glucose oxidation, thereby increasing cardiac efficiency. Trimetazidine has been proven to reduce ischemia–reperfusion injury in animal models.2 This observation has encouraged the initiation of clinical trials assessing trimetazidine for myocardial protection during PCI.
A double-blind, randomized, placebo-controlled study of patients with incapacitating angina pectoris refractory to intensive medical therapy found that trimetazidine delayed ST-segment shift associated with coronary occlusion, attenuated maximum ST-segment elevation, and decreased maximum T-wave changes.3 These results have been confirmed by a larger, more-recent trial that reported a significant reduction in average and maximum ST-segment elevation, a prolonged time between balloon inflation and patient-reported pain, a reduced time between balloon deflation and relief of pain, and a decrease in troponin levels 12 h after the procedure.4 In patients undergoing CABG surgery, the mean troponin T levels measured 5 min after completion of cardiopulmonary bypass were significantly lower in patients treated with trimetazidine than in those who received placebo.5
The cardioprotective effects of trimetazidine during PCI have been confirmed in a prospective, randomized study by Bonello and colleagues, conducted in 266 patients undergoing single-vessel stenting. Oral administration of trimetazidine significantly reduced post-PCI elevation of cTnI—a marker of cardiac damage—compared with no treatment, although it did not reduce the frequency of cTnI release. Unfortunately no information was provided on the prognostic effect of this strategy, and no explanation was given for the exclusion of patients receiving more than one balloon inflation.
The observations made by Bonello et al. add to evidence from previous reports demonstrating that cardioprotection can be achieved early after a single oral administration of trimetazidine. Previous studies have, however, used either injectable formulations that are not commercially available, or prolonged oral pretreatment that is unpractical in busy catheterization laboratories. Although trimetazidine has been shown to exert a substantial cardioprotective effect and to markedly attenuate biochemical, mechanical and electrocardiographic markers of myocardial damage, large studies focused on clinical end points are warranted before routine use of trimetazidine during PCI can be recommended.
Acknowledgments
The synopsis was written by Alexandra King, Associate Editor, Nature Clinical Practice.
References
- Simoons ML et al. (1999) Minimal myocardial damage during coronary intervention is associated with impaired outcome. Eur Heart J 20: 1112–1119 | Article | PubMed | ISI | ChemPort |
- Stanley WC and Marzilli M (2003) Metabolic therapy in the treatment of ischemic heart disease: the pharmacology of trimetazidine. Fundam Clin Pharmacol 17: 133–145 | Article | PubMed | ISI | ChemPort |
- Kober G et al. (1993) Myocardial cytoprotection during percutaneous transluminal coronary angioplasty. Eur Heart J 14 (Suppl G): S6–S11
- Polonski l et al. (2002) Trimetazidine limits the effects of myocardial ischemia during percutaneous coronary angioplasty. Curr Med Res Opin 18: 389–396 | Article | PubMed | ISI | ChemPort |
- Tünerir B et al. (1999) Measurement of troponin T to detect cardioprotective effect of trimetazidine during coronary artery bypass grafting. Ann Thorac Surg 68: 2173–2176 | Article | PubMed |
Competing interests
The author declared no competing interests.
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Subject areas under which this article appears: Intervention | Therapy
