Trimetazidine in Heart Failure: From Metabolic Modulation to Clinical Outcomes—A Narrative Review

Heart Failure (HF) remains a leading cause of morbidity and mortality worldwide despite major advances in guideline-directed medical therapy. Metabolic remodeling with impaired myocardial energy utilization has emerged as an important therapeutic target in HF. Trimetazidine, a metabolic modulator that partially inhibits fatty acid beta-oxidation and favours glucose oxidation, enhances myocardial energy efficiency without changing systemic hemodynamics. This narrative review summarizes the molecular mechanisms underlying the cardioprotective effects of trimetazidine and critically evaluates the available clinical evidence supporting its use in HF. Experimental studies have shown that trimetazidine increases ATP production, maintains mitochondrial function, decreases oxidative stress, inhibits apoptosis of cardiomyocytes, regulates autophagy, and reduces myocardial inflammation and fibrosis. Clinical studies and meta-analyses have shown that adjunctive therapy with trimetazidine has been associated with improved left ventricular ejection fraction, ventricular remodeling, exercise capacity, New York Heart Association functional class, biomarkers of myocardial injury, and quality of life in patients with heart failure with reduced ejection fraction. The available evidence also indicates reductions in cardiovascular hospitalization and possibly all-cause mortality, but these findings are based primarily on relatively small randomized trials and pooled analyses, and need confirmation in adequately powered multicenter studies. The potential role of trimetazidine alongside contemporary therapies, including sodium-glucose cotransporter-2 inhibitors and other guideline-directed treatments, is also discussed. Overall, trimetazidine appears to be a promising adjunctive metabolic therapy that may complement existing pharmacological strategies in selected patients with heart failure (Central Illustration). Further large-scale clinical trials are needed to better define its place in contemporary HF management.