Trimetazidine in Acute Coronary Syndrome
Trimetazidine is NOT recommended for routine use in acute coronary syndrome (ACS), as the highest quality evidence shows no benefit on clinical outcomes, and current ESC guidelines do not include it in ACS management protocols. 1, 2
Evidence Against Routine Use in ACS
The most definitive evidence comes from the ATPCI trial (2020), the largest and most recent randomized controlled trial examining trimetazidine in post-ACS patients 2:
- 6,007 patients were randomized to trimetazidine 35 mg twice daily versus placebo after successful PCI for either stable angina or ACS (unstable angina/NSTEMI) 2
- After median follow-up of 47.5 months, trimetazidine showed no significant difference in the primary composite endpoint of cardiac death, hospital admission for cardiac events, recurrence/persistence of angina, or need for coronary angiography (23.3% vs 23.7%, HR 0.98,95% CI 0.88-1.09, p=0.73) 2
- No individual component of the primary endpoint showed benefit, including cardiac death, angina recurrence, or need for additional antianginal therapy 2
- Results were consistent regardless of whether patients had elective or urgent PCI 2
Guideline Recommendations
ESC Guidelines for ACS Management
The 2015 ESC Guidelines for NSTE-ACS management do not mention trimetazidine in their treatment algorithms or pharmacological recommendations 1. The 2011 ESC ACS guidelines similarly make no reference to trimetazidine as part of acute or post-ACS management 1.
ESC Guidelines for Chronic Coronary Syndromes
The 2024 ESC Guidelines for Chronic Coronary Syndromes (CCS) have downgraded trimetazidine from its previous position 1:
- Class IIb recommendation (may be considered) as add-on therapy only when symptoms are inadequately controlled on beta-blockers and/or calcium channel blockers 1
- This represents a demotion from 2019 guidelines, where it had Class IIa recommendation 1
- Trimetazidine is explicitly positioned as a second-line agent for chronic stable angina, not for ACS 1
Mechanism and Rationale
Trimetazidine is a metabolic modulator that inhibits mitochondrial 3-ketoacyl-CoA thiolase, shifting myocardial metabolism from fatty acid oxidation to glucose utilization 1. Unlike traditional antianginal agents, it does not affect hemodynamic parameters (heart rate, blood pressure) 1, 3.
While this mechanism theoretically could protect ischemic myocardium during ACS, the ATPCI trial definitively showed this does not translate to clinical benefit in the post-ACS setting 2.
Limited Supporting Evidence
Some older, smaller studies suggested potential benefits 4, 5:
- A 2021 observational study (570 patients) suggested trimetazidine added to optimal medical therapy reduced oxidative stress and major cardiovascular events in NSTE-ACS patients at 5 years 4
- A 2007 study (52 patients) showed reduced troponin elevation and improved left ventricular function after PCI 5
However, these small studies are superseded by the large, well-designed ATPCI trial showing no benefit 2.
Clinical Bottom Line
For patients presenting with ACS:
- Focus on guideline-directed medical therapy: dual antiplatelet therapy, beta-blockers (especially if prior MI or reduced ejection fraction), ACE inhibitors/ARBs, and high-intensity statins 1
- Do not add trimetazidine during the acute phase or immediate post-ACS period, as it provides no mortality or morbidity benefit 2
- If persistent angina develops months after ACS despite optimal first-line antianginal therapy (beta-blockers, calcium channel blockers), trimetazidine may be considered as third-line add-on therapy, but long-acting nitrates or ranolazine should be preferred (Class IIa) 1
Special Consideration
Trimetazidine may be a reasonable option in chronic coronary syndrome patients with low heart rate and/or blood pressure who cannot tolerate rate-lowering or blood pressure-lowering antianginal agents 1. However, this applies to stable chronic disease, not acute coronary syndromes 1.