Trimetazidine is an oral anti-anginal drug, sold as Vastarel and under other trade names. It works differently from most heart drugs: instead of lowering heart rate or blood pressure, it shifts how heart cells make energy, from burning fat toward burning glucose. It was first authorized in France in 1978 and is used in Europe and many other countries, but it has never been approved by the US FDA (Brie et al., Pharmaceuticals 2026).
In 2012 the European Medicines Agency (EMA) narrowed its use to one indication: an add-on treatment for stable angina that is not controlled by first-line drugs. The review also added warnings about drug-induced parkinsonism. Trimetazidine is on the WADA Prohibited List as a metabolic modulator, banned at all times, and it has been a common finding in doping-control samples.
This page summarizes what the EMA review, clinical trials and anti-doping research report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Anti-anginal “metabolic agent”; piperazine derivative |
| Brands | Vastarel and other trade names; first authorized in France in 1978 |
| Route and forms (EU) | Oral: 20 mg tablet, 20 mg/mL oral drops, 35 mg modified-release (MR) tablet |
| Labeled dose (EU) | 35 mg MR twice daily, or 20 mg three times daily, with meals |
| Half-life | ≈6.4–7.8 h after single MR doses in healthy adults; longer in older adults |
| Mechanism | Inhibits long-chain 3-ketoacyl-CoA thiolase, the last step of fat oxidation |
| EU status | Add-on therapy for stable angina only (EMA review, 2012) |
| US status | Never approved by the FDA |
| WADA status | Prohibited at all times; S4.4.4 metabolic modulators; non-specified substance |
What it is
Trimetazidine is a small synthetic molecule, 1-[(2,3,4-trimethoxyphenyl)methyl]piperazine, with the formula C₁₄H₂₂N₂O₃ and a molecular weight of 266.34 g/mol (PubChem). It is not a hormone and has no anabolic or androgenic activity. It shares its piperazine core with the drugs flunarizine and cinnarizine, which are also known to cause movement disorders (Masmoudi et al., Fundam Clin Pharmacol 2012).
The heart normally gets most of its energy from burning fatty acids. Burning glucose yields more energy per unit of oxygen, which matters when blood flow is restricted (ischemia). Trimetazidine blocks the long-chain form of 3-ketoacyl-CoA thiolase, the last enzyme in fatty-acid beta-oxidation. This pushes the heart toward glucose oxidation (EMA Annex III).
The key mechanistic study used isolated working rat hearts (Kantor et al., Circ Res 2000):
| Finding (rat hearts) | Result |
|---|---|
| Long-chain 3-ketoacyl-CoA thiolase inhibition | IC50 75 nmol/L |
| Medium- and short-chain forms of the enzyme | Needed over 10 and over 100 µmol/L |
| Palmitate (fat) oxidation | Fell from 488 to 408 nmol/g dry weight/min |
| Glucose oxidation | Rose from 1,889 to 2,378 nmol/g dry weight/min |
| Glucose oxidation during low-flow ischemia | Increased by 210% |
| Oxygen use and cardiac work | No change |
The EMA describes trimetazidine as having no effect on blood pressure or heart rate (EMA Annex II). This is why it is used on top of drugs such as beta-blockers rather than instead of them.
Pharmacokinetics
In a single ascending-dose study, 18 healthy adults took one 35, 70 or 105 mg MR tablet (Körnicke et al., Drug Res 2020):
| Single MR dose | Peak level (Cmax) | Time to peak | Half-life |
|---|---|---|---|
| 35 mg | 79.3 ng/mL | 5.4 h | 7.75 h |
| 70 mg | 153.2 ng/mL | 4.5 h | 6.40 h |
| 105 mg | 199.7 ng/mL | 4.6 h | 6.50 h |
Total exposure rose less than in proportion to the dose, so the drug’s kinetics are not linear at higher doses.
Trimetazidine is cleared mainly by the kidneys as unchanged drug (Brie et al., Pharmaceuticals 2026). This makes kidney function and age important:
- In healthy older adults taking 35 mg MR twice daily, the half-life was significantly longer and renal clearance lower than in younger adults (Barré et al., Biopharm Drug Dispos 2003).
- In moderate and severe kidney failure, exposure rose significantly. Creatinine clearance correlated closely with drug exposure (r = −0.94).
- The EMA noted that serious adverse events were more frequent in older patients with high plasma levels, and added dose reductions for these groups (EMA Annex II).
Approved medical use
Trimetazidine was once authorized in Europe for three uses: preventing angina attacks, and as a supporting treatment for vertigo and tinnitus and for vision problems of vascular origin. In a French prescription study cited by the EMA, 30% of prescriptions were for ear, nose and throat conditions and 24.3% had no known indication (EMA Annex II).
France asked the EMA to review the drug in April 2011, citing weak evidence of benefit and reports of parkinsonism. In June 2012 the EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded (EMA referral page; EMA press release, 2012):
- Angina: benefits still outweigh risks, but only as add-on therapy in patients not controlled by, or intolerant to, first-line anti-anginal drugs.
- Tinnitus, vertigo and vision disturbances: benefits no longer outweigh risks, and these uses were removed.
- New safety measures: contraindications for movement disorders and severe kidney impairment, and a warning on parkinsonism.
The resulting EU product information sets out the doses (EMA Annex III):
| Patient group | 35 mg MR tablet | 20 mg tablet or 20 mg/mL drops |
|---|---|---|
| Adults | 1 tablet twice daily with meals | 20 mg three times daily with meals |
| Moderate kidney impairment (creatinine clearance 30–60 mL/min) | 1 tablet in the morning with breakfast | 20 mg twice daily |
| Severe kidney impairment (creatinine clearance under 30 mL/min) | Contraindicated | Contraindicated |
| Children under 18 | Safety and efficacy not established | Safety and efficacy not established |
The label also advises caution in patients over 75. The 2024 European Society of Cardiology guideline on chronic coronary syndromes moved trimetazidine from class IIa to class IIb (“may be considered”). The 2023 AHA/ACC guideline does not include it, mainly because it was never approved in the US (Brie et al., Pharmaceuticals 2026).
What the research shows
Stable angina symptoms
A 2005 Cochrane review pooled 23 randomized trials with 1,378 patients (Ciapponi et al., Cochrane 2005). Compared with placebo, trimetazidine:
- reduced weekly angina attacks by a mean of 1.44 (95% CI 0.79–2.10 fewer);
- reduced weekly use of nitroglycerin tablets;
- lengthened exercise time before 1 mm ST-segment depression (an ECG sign of ischemia).
The review found little data on mortality, cardiovascular events or quality of life, and called for large long-term trials. Cochrane later withdrew the review (Cochrane 2017).
The EMA based the add-on indication mainly on three trials in patients already taking a beta-blocker (EMA Annex II):
| Trial | Design and n | Main result vs placebo |
|---|---|---|
| TRIMPOL-II | 426 patients; 60 mg/day added to metoprolol for 12 weeks | Total exercise duration +20.1 s; time to angina +33.9 s; 0.73 fewer angina attacks/week |
| Sellier | 223 patients; 35 mg MR twice daily added to atenolol for 8 weeks | Time to 1 mm ST depression +34.4 s (n=173 subgroup); no difference in total exercise duration |
| VASCO | 1,962 patients; 70 or 140 mg/day added to atenolol for 3 months | No benefit overall; post-hoc gain only in symptomatic patients at 140 mg/day |
The gains are measured in seconds on a treadmill test. In the Sellier trial, the published primary result was a 44-second greater increase in time to ST depression (p = 0.005) (Sellier and Broustet, Am J Cardiovasc Drugs 2003).
Long-term outcomes after stenting: ATPCI
ATPCI was the long-term trial the EMA asked for. It randomized 6,007 patients at 365 centers in 27 countries who had undergone a successful percutaneous coronary intervention (PCI, a stent or balloon procedure) within the previous 30 days. They took 35 mg MR twice daily or placebo on top of standard treatment (Ferrari et al., Lancet 2020):
| Outcome (median 47.5 months) | Trimetazidine (n=2,998) | Placebo (n=3,009) |
|---|---|---|
| Primary composite: cardiac death, cardiac hospitalization, or angina needing more drugs or angiography | 23.3% | 23.7% |
| Hazard ratio | 0.98 (95% CI 0.88–1.09); p = 0.73 | — |
| Serious treatment-emergent adverse events | 40.9% | 41.1% |
None of the individual components differed between groups. The authors concluded that routine long-term use after PCI did not affect angina recurrence or outcomes, and that no significant safety concerns were seen in this population.
Heart failure
Trimetazidine is not authorized for heart failure in the EU. A 2012 meta-analysis of 16 small randomized trials with 884 patients with chronic heart failure reported (Zhang et al., JACC 2012):
| Outcome | Effect of trimetazidine |
|---|---|
| Hospitalization for cardiac causes | RR 0.43 (p = 0.03) |
| All-cause mortality | RR 0.47 (not significant, p = 0.27) |
| Left ventricular ejection fraction | +6.46 percentage points |
| Total exercise time | +63.75 s |
In heart failure with preserved ejection fraction (HFpEF), a randomized crossover trial in 25 patients found no effect on exercise filling pressures, on heart energy status measured by MR spectroscopy, or on 6-minute walk distance (van de Bovenkamp et al., ESC Heart Fail 2023).
Healthy people and athletes
There is no good evidence that trimetazidine improves performance in healthy people. A 2023 systematic review screened 2,673 publications and found only two trials in healthy people that met its criteria (Bezuglov et al., Eur Rev Med Pharmacol Sci 2023). It concluded that no data show a benefit for physical performance or recovery, and that use is linked to relatively common side effects.
One of these was a randomized trial in 39 healthy young adults taken quickly to high altitude (Yang et al., Biomed Pharmacother 2019). Taking 20 mg three times daily from 14 days before the trip reduced high-altitude fatigue (p = 0.038) and lowered lactate compared with placebo. This was a study of altitude illness, not of sports performance.
About “endurance” claims. Trimetazidine is often described as a recovery or endurance aid, by analogy with its anti-ischemic effect in diseased hearts. That effect was shown in patients with blocked coronary arteries. No controlled trial has shown better performance or recovery in healthy athletes.
Side effects and risks
Parkinsonism and other movement disorders
This is the main safety concern, and it is why the EMA restricted the drug. Trimetazidine can cause or worsen parkinsonian symptoms (tremor, slow movement, muscle stiffness), gait instability and restless legs syndrome (EMA Annex III). The EU label says:
- it is contraindicated in Parkinson disease, parkinsonian symptoms, tremor, restless legs syndrome and related movement disorders;
- any such disorder should lead to permanent withdrawal of the drug;
- most patients recover within 4 months of stopping, and a neurologist should be consulted if symptoms persist beyond that.
The EMA estimated the incidence of reported extrapyramidal symptoms at 0.36 per 100,000 person-years from spontaneous reports. It also noted that some patients only partly recovered (EMA Annex II). Spontaneous reports undercount events, and population data suggest a larger effect:
| Study | Design | Finding |
|---|---|---|
| Kim et al., IJERPH 2020 | South Korean claims data; 9,712 users vs 29,116 matched non-users | Parkinsonism 9.34 vs 6.71 per 1,000 person-years; adjusted HR 1.38 (95% CI 1.26–1.51); risk rose with cumulative dose |
| Masmoudi et al., Fundam Clin Pharmacol 2012 | French case series, 21 patients, mean age 74 | Symptoms disappeared after stopping in 16; improved in the other 5 |
| Pintér et al., Parkinsonism Relat Disord 2019 | 33 consecutive users with new parkinsonism | Fully resolved in 11 after stopping; among those scanned, persisting cases had abnormal dopamine-transporter scans, suggesting underlying Parkinson disease |
Other adverse effects
The EU label lists these (EMA Annex III):
| Frequency | Effects |
|---|---|
| Common | Dizziness, headache, abdominal pain, diarrhea, indigestion, nausea, vomiting, rash, itching, hives, weakness |
| Rare | Palpitations, extra heartbeats, fast heart rate, low blood pressure on standing (with possible falls), flushing |
| Frequency not known | Sleep problems, constipation, acute generalized exanthematous pustulosis (a severe skin reaction), angioedema, agranulocytosis (very low white cells), low platelets, hepatitis |
Falls can occur from gait instability or low blood pressure, especially in people taking blood-pressure medicines. Dizziness and drowsiness may affect driving.
Who should not take it
Per the EU label, trimetazidine is contraindicated in:
- people with Parkinson disease or other movement disorders listed above;
- severe kidney impairment (creatinine clearance under 30 mL/min);
- hypersensitivity to the drug.
It needs a lower dose in moderate kidney impairment and caution in people over 75. It is not recommended under age 18.
Legal status and use in sport
Trimetazidine is a prescription medicine in the EU and has never been approved in the US.
WADA first prohibited trimetazidine in January 2014 (Sigmund et al., Drug Test Anal 2014). Looking back at samples tested at the Cologne anti-doping laboratory between 1999 and 2013, that study found it was common, particularly in endurance and strength sports, with up to 39 findings per year. In the 2026 List it is named under S4.4.4 metabolic modulators, alongside meldonium in S4.4.3. It is prohibited in and out of competition and is a non-specified substance (WADA 2026 Prohibited List).
One complication for testing: lomerizine, a drug that is not prohibited, is broken down to trimetazidine. Laboratories therefore look for markers of lomerizine before attributing a finding to trimetazidine itself (Okano et al., Drug Test Anal 2024).
Key takeaways
- A metabolic anti-anginal, not an anabolic. It blocks the last step of fat oxidation so the heart burns more glucose, without changing heart rate or blood pressure.
- Narrow approved use. Since 2012 the EU allows it only as add-on therapy for stable angina not controlled by first-line drugs. It has never been FDA-approved.
- Modest benefits. It adds seconds of exercise time and reduces angina attacks in patients, but in the 6,007-patient ATPCI trial it did not improve outcomes after stenting.
- Movement disorders are the key risk. It can cause reversible parkinsonism, especially in older adults; one cohort found a 38% higher adjusted risk in users.
- No proven performance benefit. A systematic review found no evidence that it improves performance or recovery in healthy people.
- Banned in sport. WADA lists it under S4.4.4 metabolic modulators, prohibited at all times.
Sources
- European Medicines Agency. Trimetazidine – referral (Article 31). EMA.
- European Medicines Agency. European Medicines Agency recommends restricting use of trimetazidine-containing medicines. Press release, June 22, 2012. EMA.
- European Medicines Agency. Trimetazidine Article 31 referral, Annex II: Scientific conclusions and grounds for variation to the terms of the marketing authorisations. 2012. EMA.
- European Medicines Agency. Trimetazidine Article 31 referral, Annex III: Amendments to relevant sections of the summary of product characteristics and package leaflet. 2012. EMA.
- National Center for Biotechnology Information. PubChem Compound Summary for CID 21109, Trimetazidine. PubChem.
- Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2000;86(5):580–588. PubMed.
- Körnicke T, Arora D, Samad A, et al. Single Ascending Dose Study to Assess Pharmacokinetic Linearity, Safety, and Tolerability of Trimetazidine - Modified Release in Healthy Human Subjects. Drug Res (Stuttg). 2020;70(10):472–477. PubMed.
- Barré J, Ledudal P, Oosterhuis B, et al. Pharmacokinetic profile of a modified release formulation of trimetazidine (TMZ MR 35 mg) in the elderly and patients with renal failure. Biopharm Drug Dispos. 2003;24(4):159–164. PubMed.
- Brie DM, Mornoș C, Tîrziu A, et al. Trimetazidine in Chronic Coronary Syndrome and Coronary Artery Disease: A Narrative Review of Clinical Efficacy, Safety, and Current Guideline Position. Pharmaceuticals (Basel). 2026;19(9):1370. PubMed.
- Ciapponi A, Pizarro R, Harrison J. Trimetazidine for stable angina. Cochrane Database Syst Rev. 2005;(4):CD003614. PubMed.
- Ciapponi A, Pizarro R, Harrison J. WITHDRAWN: Trimetazidine for stable angina. Cochrane Database Syst Rev. 2017;3(3):CD003614. PubMed.
- Sellier P, Broustet JP. Assessment of anti-ischemic and antianginal effect at trough plasma concentration and safety of trimetazidine MR 35 mg in patients with stable angina pectoris: a multicenter, double-blind, placebo-controlled study. Am J Cardiovasc Drugs. 2003;3(5):361–369. PubMed.
- Ferrari R, Ford I, Fox K, et al. Efficacy and safety of trimetazidine after percutaneous coronary intervention (ATPCI): a randomised, double-blind, placebo-controlled trial. Lancet. 2020;396(10254):830–838. PubMed.
- Zhang L, Lu Y, Jiang H, et al. Additional use of trimetazidine in patients with chronic heart failure: a meta-analysis. J Am Coll Cardiol. 2012;59(10):913–922. PubMed.
- van de Bovenkamp AA, Geurkink KTJ, Oosterveer FTP, et al. Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross-over trial. ESC Heart Fail. 2023;10(5):2998–3010. PubMed.
- Bezuglov E, Zholinsky A, Shoshorina M, et al. The application of trimetazidine in healthy individuals: a systematic review. Eur Rev Med Pharmacol Sci. 2023;27(14):6882–6889. PubMed.
- Yang J, Zhang L, Liu C, et al. Trimetazidine attenuates high-altitude fatigue and cardiorespiratory fitness impairment: A randomized double-blinded placebo-controlled clinical trial. Biomed Pharmacother. 2019;116:109003. PubMed.
- Masmoudi K, Masson H, Gras V, Andréjak M. Extrapyramidal adverse drug reactions associated with trimetazidine: a series of 21 cases. Fundam Clin Pharmacol. 2012;26(2):198–203. PubMed.
- Kim S, Yu YM, Kwon J, et al. Trimetazidine Use and the Risk of Parkinsonism: A Nationwide Population-Based Study. Int J Environ Res Public Health. 2020;17(19):7256. PubMed.
- Pintér D, Kovács M, Harmat M, et al. Trimetazidine and parkinsonism: A prospective study. Parkinsonism Relat Disord. 2019;62:117–121. PubMed.
- Sigmund G, Koch A, Orlovius AK, et al. Doping control analysis of trimetazidine and characterization of major metabolites using mass spectrometric approaches. Drug Test Anal. 2014;6(11-12):1197–1205. PubMed.
- Okano M, Miyamoto A, Ota M, et al. Doping control analysis of trimetazidine in dried blood spot. Drug Test Anal. 2024;16(8):766–776. PubMed.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.