What is the role of trimetazidine in the treatment of ischemic cardiomyopathy?

Trimetazidine in Ischemic Cardiomyopathy

Trimetazidine may be considered as an add-on therapy in patients with ischemic cardiomyopathy who have inadequate control of symptoms while on treatment with beta-blockers and/or calcium channel blockers. 1

Mechanism of Action and Benefits

• Trimetazidine is a metabolic modulator that increases cellular tolerance to ischemia by inhibiting mitochondrial 3-ketoacyl-CoA thiolase, shifting cardiac metabolism from fatty acid to glucose utilization 2
• This metabolic shift improves myocardial efficiency without affecting hemodynamic parameters (heart rate, blood pressure), making it particularly useful for patients with low blood pressure or heart rate 2, 3
• Treatment with trimetazidine for 3 months increases myocardial high-energy phosphate levels by 33% in heart failure patients 2
• Trimetazidine protects the heart from the deleterious effects of ischemia and enhances left ventricular contractility in patients with stunned or hibernating myocardium 4

Place in Therapy for Ischemic Cardiomyopathy

• According to the 2024 ESC guidelines, trimetazidine has a Class IIb recommendation as an add-on therapy in patients with inadequate symptom control despite beta-blockers and/or calcium channel blockers 1
• Trimetazidine can be considered as part of initial treatment in properly selected patients, particularly those with contraindications to first-line agents 1
• Trimetazidine is a reasonable option as part of antianginal combination therapy in patients with low heart rate and/or blood pressure 1
• In patients with ischemic cardiomyopathy, trimetazidine has been shown to improve symptoms, left ventricular ejection fraction, and have beneficial effects on inflammatory profile and endothelial function 4

Clinical Evidence in Ischemic Cardiomyopathy

• A randomized controlled trial showed that trimetazidine added to conventional treatment significantly reduced all-cause mortality by 56% (hazard ratio 0.258; 95% CI, 0.097 to 0.687) and heart failure hospitalizations by 47% in patients with ischemic cardiomyopathy over 48 months 5
• In patients with ischemic dilated cardiomyopathy, trimetazidine therapy for 6 months resulted in significantly higher number of patients in NYHA class I (22% vs. 8%) and class II (56% vs. 34%), with fewer hospitalizations for worsening heart failure compared to placebo 6
• PET-CT imaging studies demonstrated that 12 months of trimetazidine treatment increased glucose metabolism in ischemic cardiomyocytes and improved left ventricular ejection fraction from 37.9% to 42.3% in patients with ischemic cardiomyopathy 7
• Trimetazidine improves the contractile response of dysfunctional myocardium in patients with ischemic heart disease and left ventricular dysfunction 8

Treatment Algorithm for Ischemic Cardiomyopathy

1. First-line therapy: Beta-blockers and/or calcium channel blockers are recommended as initial treatment for most patients with chronic coronary syndrome 1, 3
2. If symptoms persist: Consider combination of beta-blocker with a dihydropyridine calcium channel blocker 1
3. Add-on therapy options when symptoms remain inadequately controlled:
   • Long-acting nitrates or ranolazine (Class IIa recommendation) 1
   • Trimetazidine or nicorandil (Class IIb recommendation) 1
4. For patients with contraindications to first-line agents: Consider trimetazidine as part of initial treatment, particularly in those with low blood pressure or heart rate 1, 3

Important Considerations and Precautions

• Trimetazidine is contraindicated in patients with Parkinson's disease, parkinsonism, and other related movement disorders 2
• Trimetazidine is not recommended in patients with severe renal impairment 2, 9
• The most common adverse effects are mild and include gastrointestinal disturbances and minor headaches 2
• When selecting combination therapy, consider the patient's hemodynamic profile, comorbidities, and tolerability 1