Key result
Mitochondrial-targeted therapies significantly reduced all-cause mortality by 38% (RR 0.62) and heart failure-related hospitalizations compared to control in patients with heart failure.
Why the study?
Mitochondrial-targeting agents show promise in animal models and early-phase trials, but their clinical efficacy in heart failure remains uncertain.
Do mitochondria-targeted therapies improve clinical outcomes and cardiac function in patients with heart failure?
Meta-Analysis (n=2,603)
Yes
Do mitochondria-targeted therapies improve clinical outcomes and cardiac function in patients with heart failure?
Relative Risk: 0.62 (95% CI 0.47–0.82)
Number Needed to Treat: 23
p-value: p=0.0007
Mitochondrial-targeted agents may serve as potential adjunctive strategies in heart failure by improving LVEF and reducing mortality and hospitalizations, though current evidence is of low certainty.
May support mitochondrial-targeted therapies in heart failure regimens; confirms mortality benefit across trials.
Introduction Mitochondrial dysfunction is recognised as a key driver of heart failure (HF) pathophysiology, contributing to oxidative stress, apoptosis, and impaired energy production in cardiomyocytes. Although therapeutic agents aimed at restoring mitochondrial function have demonstrated promise in animal models and early-phase clinical trials, their efficacy in clinical practice remains uncertain. This meta-analysis evaluated the impact of these agents on clinical outcomes in HF patients. Methods A systematic literature search was conducted across PubMed, Cochrane Library, ScienceDirect, Google Scholar, and ClinicalTrials.gov for studies published through May 2025. Thirty one studies (24 RCTs and 7 crossover trials) were included in meta-analysis. Standardized mean difference was pooled for changes in left ventricular ejection fraction (LVEF), NYHA class and six-minute walk test (6MWT) distance compared to baseline, and risk ratios (RR) were pooled for heart failure-related hospitalisations, and all-cause mortality. Results Interventions significantly improved LVEF compared with baseline (SMD: 0.53; 95% CI: 0.42–0.65; p < 0.00001) and control groups (SMD: 0.42; 95% CI: 0.31–0.53). Treatment reduced NYHA functional class (RR: 2.38; 95% CI: 1.48–3.84; p = 0.0004), all-cause mortality (RR: 0.62; 95% CI: 0.47–0.82; p = 0.0007), and HF-related hospitalizations (RR: 0.60; 95% CI: 0.42–0.85; p = 0.004). The certainty of evidence was rated as low across all outcomes owing to substantial heterogeneity and high risk of bias. Discussion These findings suggest a potential role for mitochondrial-targeted agents as adjunctive strategies in HF, although the evidence base requires further strengthening through high-quality, adequately powered trials before firm clinical recommendations can be made. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251075951 , PROSPERO CRD420251075951.
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Mohammed et al. (2026) conducted a meta-analysis in Heart Failure (HFrEF and HFpEF) (n=2,603). Mitochondrial-targeted therapies (elamipretide, coenzyme Q10, trimetazidine, resveratrol, levocarnitine, cyclosporin) vs. Placebo or standard of care was evaluated on All-cause mortality (RR 0.62, 95% CI 0.47-0.82, p=0.0007). Mitochondrial-targeted therapies significantly reduced all-cause mortality by 38% (RR 0.62) and heart failure-related hospitalizations compared to control in patients with heart failure.
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