Is trimetazidine beneficial in the acute management of adult patients with ST‑elevation or non‑ST‑elevation myocardial infarction?

Trimetazidine is NOT Recommended for Acute Myocardial Infarction

Trimetazidine should not be used in the acute management of ST-elevation or non-ST-elevation myocardial infarction, as it is not included in evidence-based guidelines and lacks proven mortality or morbidity benefit in this setting.

Guideline-Directed Therapy Takes Priority

The 2017 European Society of Cardiology guidelines for acute myocardial infarction management make no mention of trimetazidine as part of the acute treatment algorithm. 1 The established acute pharmacotherapy includes:

• Immediate dual antiplatelet therapy with aspirin plus a potent P2Y12 inhibitor (prasugrel or ticagrelor preferred over clopidogrel) 1
• Beta-blockers (oral therapy indicated in patients with heart failure and/or LVEF <40%; intravenous administration should be considered in hemodynamically stable patients undergoing primary PCI) 1
• High-intensity statin therapy started as early as possible 1
• ACE inhibitors in patients with LVEF <40%, heart failure, hypertension, or diabetes 1
• Mineralocorticoid receptor antagonists (eplerenone) in patients with LVEF <40% and heart failure, which reduced total mortality by 15% in the EPHESUS trial 1

Evidence for Trimetazidine is Insufficient

While trimetazidine is approved in some countries as second-line add-on therapy for stable angina in patients inadequately controlled on first-line agents, 2, 3 the evidence for acute MI is problematic:

Mixed and Contradictory Trial Results

• The largest randomized trial (EMIP-FR, n=19,725) found no overall mortality benefit at 35 days (P=0.98) 4
• In thrombolysed patients, there was a trend toward increased mortality with trimetazidine (11.3% vs 10.5%, P=0.15) 4
• Only in non-thrombolysed patients was there a potential benefit (13.3% vs 15.1%, P=0.027 in per-protocol analysis), but this subgroup finding is hypothesis-generating at best 4

Surrogate Endpoints Only

• A small pilot trial (n=94) showed earlier ST-segment resolution but no difference in infarct size or left ventricular function at day 14 5
• Meta-analyses report reduced major adverse cardiac events (MACE) but acknowledge studies were underpowered for mortality endpoints 6, 3

Lack of Guideline Support

• Trimetazidine is not mentioned in the comprehensive ESC STEMI guidelines covering acute pharmacotherapy 1, 7, 8, 9
• Its role remains limited to stable coronary artery disease as add-on therapy, not acute presentations 2, 3

Clinical Algorithm for Acute MI Management

Focus on proven therapies that reduce mortality and morbidity:

1. Immediate reperfusion (primary PCI within 90-120 minutes or fibrinolysis if PCI unavailable) 7, 8, 9
2. Aspirin 75-100 mg immediately 1, 7, 8
3. Potent P2Y12 inhibitor (prasugrel or ticagrelor) before or at time of PCI 1, 7, 8
4. Anticoagulation (unfractionated heparin for PCI; enoxaparin preferred for fibrinolysis) 7, 8, 9
5. Beta-blocker (oral within 24 hours if hemodynamically stable; IV at presentation if SBP >120 mmHg and no heart failure) 1
6. High-intensity statin started immediately 1
7. ACE inhibitor (especially if LVEF <40%, heart failure, hypertension, or diabetes) 1
8. Mineralocorticoid receptor antagonist if LVEF <40% and heart failure 1

Critical Pitfalls to Avoid

• Do not substitute trimetazidine for proven mortality-reducing therapies like beta-blockers, ACE inhibitors, or mineralocorticoid receptor antagonists 1
• Do not delay guideline-directed reperfusion and pharmacotherapy to administer unproven adjunctive agents 7, 8, 9
• Do not extrapolate evidence from stable angina to acute MI—these are fundamentally different clinical scenarios with different treatment goals 2, 3

The priority in acute MI is immediate reperfusion and evidence-based pharmacotherapy that reduces mortality—trimetazidine does not meet this standard. 1, 7, 8