What is the use of Trimetazidine (anti-anginal medication)?

From the Guidelines

Trimetazidine should be considered as add-on therapy in patients with inadequate control of symptoms while on treatment with beta-blockers and/or CCBs, or as part of initial treatment in properly selected patients, according to the 2024 ESC guidelines for the management of chronic coronary syndromes 1.

Key Points

• Trimetazidine is a medication used to treat angina pectoris by improving cellular metabolism rather than affecting hemodynamics.
• The standard dosage is typically 20 mg three times daily or 35 mg modified-release tablets twice daily.
• Treatment is usually long-term for chronic angina patients.
• Trimetazidine optimizes energy production in heart cells by shifting metabolism from fatty acid oxidation to glucose utilization, which requires less oxygen and improves cardiac efficiency during ischemia.
• Common side effects include gastrointestinal disturbances, headaches, and rarely movement disorders.
• It's contraindicated in Parkinson's disease, severe renal impairment, and pregnancy.
• Trimetazidine is not approved in all countries (including the United States) and is classified as a prohibited substance by the World Anti-Doping Agency due to its potential performance-enhancing effects.

Clinical Use

• Patients should take trimetazidine with meals, continue their other cardiac medications, and have regular follow-up appointments to assess efficacy and monitor for side effects.
• The 2024 ESC guidelines recommend considering trimetazidine as a second-line treatment to reduce angina frequency and improve exercise tolerance in subjects who cannot tolerate, have contraindications to, or whose symptoms are not adequately controlled by beta-blockers, CCBs, and long-acting nitrates 1.
• The guidelines also suggest that nicorandil or trimetazidine may be considered as add-on therapy in patients with inadequate control of symptoms while on treatment with beta-blockers and/or CCBs, or as part of initial treatment in properly selected patients 1.

Mechanism of Action

• Trimetazidine increases cellular tolerance to ischemia by inhibiting the mitochondrial 3-ketoacyl-CoA thiolase and, consequently, by increasing glucose metabolism 1.
• This leads to a reduction in free fatty acid oxidation and an increase in glucose utilization by the ischemic myocardium.
• The net consequences of these effects are a reduction in proton and lactic acid production from the ischemic myocardium, and more anaerobic ATP production from the cytosol.

From the Research

Trimetazidine Overview

• Trimetazidine is an antianginal agent that increases cell tolerance to ischemia by maintaining cellular homeostasis 2, 3.
• It is used to treat stable angina pectoris and has been shown to reduce the frequency of anginal attacks and improve exercise capacity 2, 4, 5.

Efficacy of Trimetazidine

• Trimetazidine has been shown to be effective in reducing angina symptoms and improving exercise capacity in patients with stable angina pectoris 2, 4, 5.
• It has been compared to other antianginal agents such as propranolol, nifedipine, and isosorbide dinitrate, and has been found to be equally effective or more effective in some cases 2, 3.
• Trimetazidine has also been shown to be effective in patients with different durations of stable angina, including those with recently diagnosed angina 4, 5.

Safety and Tolerability of Trimetazidine

• Trimetazidine has been found to be well-tolerated and safe, with a low incidence of adverse events 2, 3.
• The most frequently reported adverse events were gastrointestinal disorders, although the incidence of these events was low 3.
• Trimetazidine has been found to be safe for long-term use, with no significant safety concerns reported in patients receiving optimal medical therapy after successful percutaneous coronary intervention (PCI) 6.

Use of Trimetazidine in Clinical Practice

• Trimetazidine is suitable for initial use as monotherapy in patients with angina pectoris and as adjunctive therapy in those with symptoms not sufficiently controlled by nitrates, beta-blockers, or calcium antagonists 3.
• The role of trimetazidine in other coronary conditions has yet to be clearly established 3.
• Trimetazidine may be considered as an option for patients with stable angina pectoris who have not responded to other treatments or who have contraindications to other antianginal agents 2, 4, 5.