Alpha-lipoic acid for long-term heart failure caused by coronary artery disease

Trial details

Who runs it

Shanghai Zhongshan Hospital

Trial code

NCT07725484

Record updated

28 October 2026

Original description

Chronic heart failure is a clinical condition caused by structural heart disease and is characterized by reduced pumping function, fluid retention, and abnormal activation of neurohormonal systems. It represents the advanced stage of many cardiovascular diseases and remains a major global health challenge. Despite progress in medical and interventional therapies, patients with chronic heart failure continue to experience high rates of death, hospitalization, and long-term disability.Read full original descriptionShow less

Lipoic Acid in Chronic Ischemic Heart Failure: Assessment of Reduction in Major Adverse Cardiovascular Events

Chronic heart failure is a clinical condition caused by structural heart disease and is characterized by reduced pumping function, fluid retention, and abnormal activation of neurohormonal systems. It represents the advanced stage of many cardiovascular diseases and remains a major global health challenge. Despite progress in medical and interventional therapies, patients with chronic heart failure continue to experience high rates of death, hospitalization, and long-term disability.

Ischemic heart failure, which develops as a result of coronary artery disease and prior myocardial infarction, is the most common form of chronic heart failure. Current treatment strategies, including guideline-directed medical therapy and revascularization procedures, can improve symptoms and outcomes but do not fully address the residual risk of adverse cardiovascular events. Therefore, additional therapeutic approaches are needed to further improve long-term prognosis in this population.

Abnormal myocardial energy metabolism is a key pathological feature of heart failure. Mitochondria play a central role in energy production, and impaired mitochondrial function contributes to disease progression. Previous studies by our group have identified mitochondrial aldehyde dehydrogenase 2 (ALDH2) as an important regulator of myocardial metabolic homeostasis and cardiac protection under ischemic and stress conditions.

Alpha-lipoic acid is a vitamin B-related compound with antioxidant properties and has been widely used in clinical practice for other indications. Increasing evidence suggests that alpha-lipoic acid may also exert protective effects in cardiovascular diseases, potentially through modulation of mitochondrial function. Experimental studies have shown that alpha-lipoic acid can restore ALDH2 activity and improve cardiac function in models of heart failure.

Based on these findings, we conducted an exploratory randomized controlled trial between 2019 and 2023 to evaluate the safety and potential efficacy of alpha-lipoic acid in patients with ischemic heart failure. In this multicenter study, patients receiving alpha-lipoic acid showed favorable trends toward reduced risk of death and heart failure-related hospitalization, as well as significant improvements in left ventricular ejection fraction and exercise capacity, without an increase in adverse events.

Taken together, prior mechanistic research and early clinical evidence support the hypothesis that alpha-lipoic acid may provide additional benefit when used as adjunctive therapy in patients with chronic ischemic heart failure. The present study is designed to further evaluate whether long-term supplementation with alpha-lipoic acid can reduce major adverse cardiovascular events and improve clinical outcomes in this population.

Inclusion: Participants must meet all of the following criteria:; Aged ≥18 years and <75 years; A history of chronic heart failure for more than 3 months or clinically documented symptoms of heart failure persisting for more than 3 months; Left ventricular ejection fraction (LVEF) <50% as assessed by echocardiography; A history of acute myocardial infarction (AMI) more than 3 months prior to enrollment; New York Heart Association (NYHA) functional class II-IV; Receipt of guideline-directed medical therapy (GDMT) for at least 2 weeks; Willingness to participate in the study, with the ability to understand and provide written informed consent.

Exclusion: Previous cardiac resynchronization therapy (CRT); Participation in another investigational drug trial within 4 weeks prior to enrollment or ongoing receipt of any investigational treatment other than the study medication; Uncontrolled malignant arrhythmias or progressively worsening unstable angina; Malignancies, lymphoma, leukemia, or other serious conditions associated with a life expectancy of less than 1 year; Known hypersensitivity or allergy to vitamin B preparations; Heart failure caused by restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, or primary valvular heart disease; Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study; Severe hepatic dysfunction, defined as serum transaminase levels exceeding 3 times the upper limit of normal (ULN), or severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²; Participants meeting any of the following criteria will be excluded:; Pregnant or breastfeeding women; Hemodynamic instability.

ClinicalTrials.gov NCT07725484