What is the role of trimetazidine in treating chest pain due to angina?

Role of Trimetazidine in Treating Angina

Trimetazidine is an effective second-line antianginal medication that improves metabolic efficiency of ischemic myocytes without affecting hemodynamics, making it particularly valuable as add-on therapy for patients with inadequate symptom control on first-line agents or those with contraindications to traditional antianginals. 1

Mechanism of Action

• 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 1
• Unlike traditional antianginal medications (beta-blockers, calcium channel blockers, nitrates), trimetazidine does not affect oxygen demand but improves the metabolic efficiency of ischemic myocytes 2
• Treatment with trimetazidine for 3 months increases myocardial high-energy phosphate levels by 33% in heart failure patients 1
• This metabolic modulation leads to less proton and lactic acid production from ischemic myocardium and more anaerobic ATP production 1

Clinical Efficacy

• Meta-analyses show trimetazidine significantly improves exercise tolerance, reduces weekly angina episodes, and decreases the use of short-acting nitrates compared to placebo 2
• Trimetazidine demonstrates antianginal effects similar to those of other antianginal agents 2
• In real-world clinical settings, adding trimetazidine to background antianginal therapy significantly decreases the frequency of angina attacks and short-acting nitrate use, regardless of angina duration 3
• Trimetazidine has shown efficacy comparable to propranolol (120-160 mg/day) and nifedipine (40 mg/day) in decreasing anginal episodes and improving exercise parameters 4

Place in Therapy

• European Society of Cardiology classifies trimetazidine as a second-line agent for patients with contraindications to first-choice agents or those who remain symptomatic despite optimal therapy 1
• Trimetazidine can be used as monotherapy or in combination with other antianginal medications, particularly calcium channel blockers or beta-blockers 1
• For patients with microvascular angina, trimetazidine is considered a potentially effective add-on therapy 2, 5
• Trimetazidine is particularly valuable for patients with hypotension as it does not exert hemodynamic effects that could further reduce blood pressure 1

Special Populations

• For patients with heart failure and angina, trimetazidine may be beneficial as add-on therapy, with potential improvements in left ventricular function 1, 6
• Trimetazidine can be considered as part of antianginal combination therapy in patients with low heart rate and/or blood pressure 1
• For patients with recently diagnosed angina and those with long-standing disease, trimetazidine has demonstrated similar efficacy in reducing angina attacks and improving quality of life 3

Safety Profile

• Treatment-related adverse effects are generally mild and well-tolerated, mostly comprising gastrointestinal disturbances such as nausea, vomiting, and minor headaches 2
• Trimetazidine is contraindicated in patients with Parkinson's disease, parkinsonism, and other related movement disorders 2, 1
• Trimetazidine is not recommended in patients with severe renal impairment (creatinine clearance <30 ml/min) 2, 1

Treatment Algorithm

1. First-line therapy: Beta-blockers and/or calcium channel blockers are recommended as initial treatment for most patients with chronic stable angina 5
2. Add-on therapy: If symptoms persist despite optimal first-line therapy, trimetazidine should be considered as add-on treatment 5, 1
3. Alternative first-line: For patients with contraindications to beta-blockers and calcium channel blockers, trimetazidine may be considered as part of initial treatment 1
4. Combination therapy: Trimetazidine can be safely combined with other antianginal medications due to its unique mechanism of action and lack of hemodynamic effects 1, 7

Common Pitfalls to Avoid

• Overlooking trimetazidine as a valuable option for patients with low blood pressure or heart rate who cannot tolerate traditional antianginals 1
• Prescribing trimetazidine to patients with Parkinson's disease or related movement disorders 2, 1
• Using trimetazidine in patients with severe renal impairment 2, 1
• Failing to recognize trimetazidine's potential benefits in specific patient populations, such as those with microvascular angina or heart failure with angina 2, 6