When to give trimetazidine (anti-anginal medication) in cardiac patients and what is its mechanism of action?

Trimetazidine in Cardiac Patients: Indications and Mechanism of Action

Trimetazidine should be considered as a second-line agent for patients with chronic angina who have contraindications to first-line agents or remain symptomatic despite optimal therapy with beta-blockers and/or calcium channel blockers. 1, 2

Mechanism of Action

• Trimetazidine increases cellular tolerance to ischemia by inhibiting mitochondrial 3-ketoacyl-CoA thiolase, which shifts cardiac metabolism from fatty acid to glucose utilization 1, 2
• Unlike traditional antianginal medications, trimetazidine does not exert hemodynamic effects (no impact on heart rate, blood pressure, or rate-pressure product) but improves the metabolic efficiency of ischemic myocytes 1, 3
• This metabolic modulation leads to less proton and lactic acid production from ischemic myocardium and more anaerobic ATP production 2
• Treatment with trimetazidine for 3 months increases myocardial high-energy phosphate levels by 33% in heart failure patients 1, 4

Clinical Indications

Primary Indication: Chronic Stable Angina

• According to the 2024 ESC guidelines, trimetazidine may be considered as add-on therapy in patients with inadequate control of symptoms while on treatment with beta-blockers and/or calcium channel blockers (Class IIb recommendation) 1
• Trimetazidine can also be considered as part of initial treatment in properly selected patients 1, 2
• In meta-analyses, trimetazidine significantly improved exercise tolerance, reduced weekly angina episodes, and decreased the use of short-acting nitrates compared to placebo 1

Special Patient Populations

• For patients with hypotension, trimetazidine is preferred as it does not further reduce blood pressure 2, 5
• Trimetazidine may provide additional benefits in patients with left ventricular dysfunction and/or heart failure as add-on therapy 4, 6
• In patients with ischemic cardiomyopathy, trimetazidine has been shown to improve left ventricular function 7
• For patients with diabetes and chronic angina, ranolazine is generally preferred over trimetazidine due to its proven benefits on glycemic control 8

Safety and Contraindications

• Trimetazidine is generally well-tolerated with mild adverse effects, primarily gastrointestinal disturbances and minor headaches 1, 2
• Trimetazidine is contraindicated in patients with:
  • Parkinson's disease, parkinsonism, and other related movement disorders 1, 2
  • Severe renal impairment (creatinine clearance <30 ml/min) 1, 2

Clinical Efficacy

• Trimetazidine 80 mg once daily added to background antianginal treatment effectively reduces the frequency of angina attacks and the use of short-acting nitrates 9
• Benefits are observed regardless of angina duration, including in recently diagnosed patients 9
• When used as monotherapy, trimetazidine's clinical effects are broadly similar to those of nifedipine 40 mg/day and propranolol 120-160 mg/day 5
• As adjunctive therapy, trimetazidine reduces the frequency of anginal attacks and improves exercise capacity in patients not sufficiently controlled by conventional antianginal agents 5

Practical Prescribing Considerations

• Standard dosing: 20 mg three times daily or 80 mg once daily (extended-release) 5, 9
• Can be used as monotherapy but more commonly used in combination with first-line agents (beta-blockers or calcium channel blockers) 2, 5
• Consider trimetazidine when hemodynamic effects of traditional antianginals are undesirable (e.g., in patients with low blood pressure) 2, 3