What is the role of trimetazidine in the management of acute coronary syndrome?

Role of Trimetazidine in Acute Coronary Syndrome

Trimetazidine is NOT recommended as part of standard acute coronary syndrome management and is not mentioned in major European or American guidelines for ACS treatment. The established therapies for ACS include dual antiplatelet therapy (aspirin plus P2Y12 inhibitor), anticoagulation, beta-blockers, statins, and ACE inhibitors—trimetazidine does not appear in these evidence-based recommendations 1, 2.

Current Guideline-Directed Therapy for ACS

The standard management of acute coronary syndromes without persistent ST-elevation focuses on:

• Antiplatelet therapy: Aspirin plus clopidogrel, ticagrelor, or prasugrel for at least 9-12 months 1, 2
• Anticoagulation: Low molecular weight heparin or unfractionated heparin 1
• Beta-blockers: Improve prognosis and should be continued after ACS 1
• Statins: Should be initiated without delay, with evidence showing mortality reduction 1
• ACE inhibitors: Reduce cardiovascular death and myocardial infarction 1
• GP IIb/IIIa inhibitors: Particularly in patients with elevated troponin undergoing percutaneous intervention 1

Evidence on Trimetazidine in ACS

While trimetazidine is approved in some countries as a second-line antianginal agent for stable coronary disease, its role in acute coronary syndromes remains uncertain and unsupported by major guidelines 3.

Mixed Evidence from Clinical Trials

The largest randomized trial (EMIP-FR) with 19,725 patients showed NO benefit of trimetazidine in ACS overall, and concerning trends emerged 4:

• In patients receiving thrombolysis, trimetazidine showed a trend toward increased mortality (11.3% vs 10.5% placebo, P=0.15) 4
• Only in non-thrombolysed patients was there a potential benefit (13.3% vs 15.1% placebo, P=0.027 in per-protocol analysis) 4
• The opposing effects in different patient subgroups raise serious safety concerns 4

Smaller Studies Show Surrogate Endpoint Benefits Only

More recent but smaller studies suggest potential benefits on surrogate markers but lack hard outcome data:

• A 2021 study of 570 patients showed trimetazidine added to optimal medical therapy reduced oxidative stress, endothelial dysfunction, and readmissions in non-ST-elevation ACS at 5 years, but this was not a placebo-controlled trial 5
• A 2007 study of 52 patients undergoing PCI showed reduced troponin elevation and improved ejection fraction, but was severely underpowered for clinical outcomes 6
• These studies demonstrate effects on biomarkers and surrogate endpoints but cannot establish mortality or morbidity benefits 3, 7

Clinical Bottom Line

Do not use trimetazidine as part of acute coronary syndrome management. Focus on guideline-directed therapies with proven mortality benefit:

1. Immediate treatment: Aspirin, P2Y12 inhibitor (ticagrelor or prasugrel preferred over clopidogrel), anticoagulation, and symptom relief with nitrates 1, 2

2. Risk stratification: Obtain troponin levels and ECG; patients with elevated troponin or high-risk features require early angiography within 24-48 hours 8

3. Long-term secondary prevention: Beta-blockers, high-intensity statins, ACE inhibitors, and continued dual antiplatelet therapy for 12 months 1, 2

Important Caveats

• Trimetazidine may be considered as add-on therapy for stable angina inadequately controlled by first-line agents, but this is a separate indication from acute coronary syndromes 3
• The EMIP-FR trial's concerning signal of potential harm in thrombolysed patients should preclude its use during the acute phase of myocardial infarction 4
• No large randomized trials have demonstrated that trimetazidine reduces death, myocardial infarction, or other major adverse cardiovascular events in ACS 3, 7