What is Trimetazidine used for?

Trimetazidine: Clinical Uses and Indications

Trimetazidine is used as a second-line antianginal agent for the symptomatic treatment of stable angina pectoris, either as add-on therapy when first-line agents (beta-blockers, calcium channel blockers) fail to adequately control symptoms, or as monotherapy in patients with contraindications to first-line medications. 1

Primary Indication: Stable Angina Pectoris

Mechanism and Metabolic Effects

• Trimetazidine functions as a metabolic modulator that increases cellular tolerance to ischemia by inhibiting mitochondrial 3-ketoacyl-CoA thiolase, thereby shifting cardiac metabolism from fatty acid to glucose utilization 2, 1
• Unlike traditional antianginal medications, trimetazidine improves metabolic efficiency of ischemic myocytes without affecting hemodynamic parameters such as heart rate, blood pressure, or oxygen demand 2, 1
• Treatment for 3 months increases myocardial high-energy phosphate levels by 33% in heart failure patients 1

Clinical Efficacy in Angina

• Meta-analyses demonstrate that trimetazidine significantly improves exercise tolerance, reduces weekly angina episodes, and decreases short-acting nitrate consumption compared to placebo 2
• The antianginal effects are similar to those of propranolol (120-160 mg/day) and nifedipine (40 mg/day), but without the hemodynamic effects 3, 4
• Clinical benefits occur rapidly (within 2 weeks) and are maintained over 6 months, regardless of angina duration 5

Place in Treatment Algorithm

As Second-Line Therapy

• The American College of Cardiology and European Society of Cardiology classify trimetazidine as a Class IIb recommendation for patients who have contraindications to first-choice agents or remain symptomatic despite optimal therapy 1
• Trimetazidine should be added when beta-blockers and/or calcium channel blockers fail to adequately control symptoms 1

As Combination Therapy

• Trimetazidine can be combined with calcium channel blockers or beta-blockers for enhanced symptom control 2, 1
• When used as adjunctive therapy at 60 mg/day, it reduces anginal attacks and nitroglycerin use in patients insufficiently controlled by conventional antianginal agents 3
• Trimetazidine appears more effective than isosorbide dinitrate (30 mg/day) when used adjunctively in patients poorly controlled by propranolol 3

Special Clinical Situations

Patients with Hypotension or Low Blood Pressure

• Trimetazidine is the preferred antianginal agent in patients with hypotension because it does not exert hemodynamic effects that could further reduce blood pressure 1
• This makes it particularly valuable in patients with low heart rate and/or blood pressure who cannot tolerate rate-lowering or blood pressure-lowering agents 1

Ischemic Cardiomyopathy and Heart Failure

• The European Society of Cardiology recommends trimetazidine as add-on therapy (Class IIb) in patients with ischemic cardiomyopathy and inadequate symptom control despite beta-blockers and/or calcium channel blockers 1
• Meta-analyses suggest trimetazidine may be beneficial as add-on therapy in patients with left ventricular dysfunction and/or heart failure 1
• Limited evidence suggests trimetazidine may improve left ventricular function in patients with chronic coronary artery disease or ischemic cardiomyopathy 3

Coronary Interventions

• Trimetazidine use during percutaneous coronary intervention and coronary artery bypass grafting shows reduction in frequency of anginal attacks and myocardial damage, though studies remain underpowered for definitive mortality benefit conclusions 6

Dosing Formulations

• Standard dosing: 20 mg three times daily 2, 3, 4
• Modified release: 35 mg twice daily 5, 7
• Extended release: 80 mg once daily, which improves adherence and maintains efficacy 7

Safety Profile and Contraindications

Generally Well-Tolerated

• Treatment-related adverse effects are mild and well-tolerated, primarily comprising gastrointestinal disturbances such as nausea, vomiting, and minor headaches 2, 1
• The tolerability profile is similar to placebo when used as add-on therapy and superior to nifedipine or propranolol when used as monotherapy 3

Absolute Contraindications

• Trimetazidine is contraindicated in patients with Parkinson disease, parkinsonism, and other related movement disorders 2, 1, 8
• Not recommended in patients with severe renal impairment (creatinine clearance <30 ml/min or GFR <30 ml/min/1.73 m²) 2, 1, 8

Comparison with Ranolazine

When to Choose Trimetazidine Over Ranolazine

• In patients with hepatic impairment or liver cirrhosis: Ranolazine is contraindicated, making trimetazidine the preferred metabolic modulator if no movement disorders exist 8
• In patients on digoxin: Trimetazidine does not affect digoxin levels, whereas ranolazine increases digoxin concentration by 40-60% 8
• In patients with movement disorders: Avoid trimetazidine and consider ranolazine 8

When to Choose Ranolazine Over Trimetazidine

• In patients with diabetes and chronic angina: Ranolazine is strongly preferred due to proven benefits on glycemic control, significantly reducing HbA1c levels 1, 8
• Ranolazine has more robust clinical evidence from contemporary, double-blind, placebo-controlled trials compared to trimetazidine's primarily historical, small, and often open-label trials 8

Key Clinical Pitfalls to Avoid

• Do not use trimetazidine in patients with any form of parkinsonism – this is an absolute contraindication that is sometimes overlooked 2, 1
• Avoid in severe renal impairment (CrCl <30 ml/min) 2, 1
• Do not expect hemodynamic effects – trimetazidine will not lower heart rate or blood pressure, so it should not be chosen if rate or blood pressure control is needed 2, 1
• Screen for diabetes – if present, ranolazine may be a better choice due to glycemic benefits 1, 8