When is Trimetazidine (anti-anginal medication) indicated for patients with angina pectoris?

When to Give Trimetazidine

Trimetazidine may be considered as add-on therapy in patients with chronic coronary syndrome who have inadequate symptom control despite treatment with beta-blockers and/or calcium channel blockers, or as part of initial treatment in properly selected patients with contraindications to first-line agents. 1

Current Guideline Position (2024 ESC Guidelines)

The most recent 2024 European Society of Cardiology guidelines downgraded trimetazidine from its previous position:

• Class IIb recommendation (Level B evidence): Trimetazidine may be considered as add-on therapy when symptoms remain inadequately controlled on beta-blockers and/or calcium channel blockers 1
• This represents a downgrade from the 2019 guidelines, which gave trimetazidine a Class IIa recommendation as second-line treatment 1
• Long-acting nitrates and ranolazine now receive preferential Class IIa recommendations over trimetazidine 1

Treatment Algorithm

First-Line Therapy

• Beta-blockers and/or calcium channel blockers remain the foundation of antianginal treatment 1
• Short-acting nitroglycerin for acute symptom relief in all patients 1

When to Add Trimetazidine

Add trimetazidine when:

1. Inadequate symptom control on optimized doses of beta-blockers and/or calcium channel blockers 1, 2
2. Contraindications or intolerance to first-line agents (beta-blockers, calcium channel blockers) 1, 2
3. Hemodynamic limitations: Patient has low blood pressure or low heart rate that precludes uptitration of hemodynamically active agents 2, 3

Specific Clinical Scenarios Favoring Trimetazidine

Hypotension

• Preferred in patients with low blood pressure because trimetazidine does not exert hemodynamic effects (does not reduce heart rate or blood pressure) 1, 2
• Unlike beta-blockers, calcium channel blockers, and nitrates, trimetazidine improves metabolic efficiency without affecting oxygen demand 1, 2

Heart Failure with Angina

• Consider trimetazidine as add-on therapy in patients with left ventricular dysfunction and persistent angina 2, 3
• Treatment for 3 months increases myocardial high-energy phosphate levels by 33% 1, 2, 3
• Only after optimizing beta-blockers, considering revascularization, and adding long-acting nitrates 3

Combination Therapy

• Trimetazidine can be combined with hemodynamically active agents (beta-blockers or calcium channel blockers) because its metabolic mechanism does not overlap with their hemodynamic effects 1
• Effective as add-on to conventional antianginal therapy in reducing weekly angina attacks (mean difference -1.44 attacks per week) 4

Important Contraindications and Precautions

Absolute Contraindications

• Parkinson's disease, parkinsonism, and related movement disorders 1, 2, 3, 5
• Severe renal impairment (creatinine clearance <30 ml/min) 1, 2, 3, 5

Relative Considerations

• Diabetes mellitus: Ranolazine is generally preferred over trimetazidine in diabetic patients due to proven benefits on glycemic control (reduces HbA1c) 1, 5
• Adverse effects are typically mild (gastrointestinal disturbances, minor headaches) and well-tolerated 1, 2, 6

Clinical Efficacy Evidence

• Reduces weekly angina attacks by approximately 1.44 episodes compared to placebo 4
• Decreases weekly nitroglycerin consumption by 1.47-2.20 tablets 4
• Improves exercise time to 1 mm ST-segment depression 4
• Benefits observed across all durations of stable angina, including recently diagnosed patients 7
• Efficacy comparable to propranolol and nifedipine in reducing anginal episodes 6

Common Pitfalls to Avoid

• Do not use trimetazidine as first-line monotherapy when beta-blockers or calcium channel blockers are appropriate and tolerated 1
• Screen for movement disorders before initiating therapy 1, 2, 3
• Check renal function before prescribing 1, 2, 3
• Consider ranolazine instead in diabetic patients for dual benefits on angina and glycemic control 1, 5
• Recognize that trimetazidine has weaker evidence compared to ranolazine, which has more robust contemporary trial data 5