Is trimetazidine (anti-anginal medication) recommended as a first-line treatment for heart failure?

Trimetazidine in Heart Failure: Not Recommended as First-Line Treatment

Trimetazidine is not recommended as a first-line treatment for heart failure but may be considered as an adjunctive therapy in specific clinical scenarios, particularly for patients with heart failure who also have angina symptoms. 1

Current Guideline Recommendations for Heart Failure

First-Line Therapies

• ACE inhibitors are the established first-line therapy for patients with reduced left ventricular systolic function (ejection fraction <40-45%), with or without symptoms 1
• Beta-blockers are strongly recommended for patients with left ventricular dysfunction, particularly when heart failure coexists with angina 1
• Diuretics are essential for symptomatic treatment when fluid overload is present 1

Role of Trimetazidine in Heart Failure Management

Mechanism of Action

• Trimetazidine is a metabolic modulator that inhibits mitochondrial 3-ketoacyl-CoA thiolase, increasing glucose metabolism and improving metabolic efficiency of ischemic myocytes 1
• Unlike traditional heart failure medications, trimetazidine does not exert hemodynamic effects but improves the metabolic efficiency of the heart 1
• Treatment with trimetazidine for 3 months has been shown to increase myocardial levels of high-energy phosphates by 33% in patients with heart failure 1

Clinical Evidence

• European guidelines have categorized trimetazidine as a class IIb recommendation (may be considered) specifically in patients with heart failure with reduced ejection fraction who also have angina 2
• Meta-analyses suggest potential benefits of trimetazidine in heart failure, including reduced cardiovascular mortality and heart failure hospitalizations, but these are based on multiple smaller trials of varying quality 3
• The most recent randomized study (2022) found no significant changes in mortality, exercise capacity, left ventricular ejection fraction, or quality of life when trimetazidine was added to standard medical therapy in stable advanced heart failure patients 4

Specific Clinical Scenarios

Heart Failure with Concomitant Angina

• For patients with heart failure and angina, the recommended approach is to:
  1. Optimize existing therapy, especially beta-blockade
  2. Consider coronary revascularization
  3. Add long-acting nitrates
  4. Consider trimetazidine only if the above measures are not successful 1

Heart Failure with Left Ventricular Dysfunction

• Beta-blockers are the evidence-based first choice for patients with left ventricular systolic dysfunction with or without heart failure 1
• Trimetazidine may be considered as an add-on therapy based on meta-analyses of small studies, but not as first-line treatment 1, 3

Safety Considerations

• Trimetazidine is generally well-tolerated with mild adverse effects (gastrointestinal disturbances, minor headaches) 1
• Contraindicated in patients with:
  • Parkinson's disease, parkinsonism, and other movement disorders 1, 5
  • Severe renal impairment (creatinine clearance <30 ml/min) 1, 5

Conclusion

While trimetazidine shows promise as an adjunctive therapy in heart failure management, particularly for patients with concomitant angina, current evidence does not support its use as a first-line treatment. ACE inhibitors, beta-blockers, and diuretics remain the cornerstone of initial heart failure therapy based on robust evidence and guideline recommendations 1.