Effectiveness and safety of coenzyme Q10 in people with heart failure with preserved ejection fraction (HFpEF): a systematic review and meta-analysis

Objectives Coenzyme Q10 (CoQ10) supplementation has previously shown efficacy in improving symptoms and outcomes for people with heart failure with reduced ejection fraction. This review aims to assess whether CoQ10 may also be effective and safe for those with heart failure with preserved ejection fraction (HFpEF).Design Systematic review and meta-analysis of randomised controlled trials.Data sources We searched databases including Embase, MEDLINE, CENTRAL, Web of Science, CINAHL, AMED, ClinicalTrials.gov and the ISRCTN registry on 25 June 2025.Eligibility criteria We included randomised controlled trials (RCTs) enrolling adults (≥18 years) with HFpEF, defined as an ejection fraction of ≥50%. Eligible studies compared any CoQ10 regimen with placebo or standard care.Data extraction and synthesis Two reviewers independently screened studies and extracted data. Risk of bias was assessed using RoB2 and the certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). We conducted random-effects pairwise meta-analysis where possible, using the RevMan V.5.4 software. Synthesis without meta-analysis was conducted for other outcomes.Results Three RCTs (264 participants) with a treatment duration of 8–24 weeks were included. The effect of CoQ10 on mortality in individuals with HFpEF was very uncertain (2/101 participants receiving CoQ10 vs 0/105 participants receiving placebo). No cardiovascular deaths occurred in either group (206 participants, very low certainty evidence). The effect of CoQ10 on hospitalisation due to heart failure was very uncertain (1/19 participants receiving CoQ10 vs 0/20 participants receiving placebo). Evidence on quality of life was mixed and also considered very uncertain, with one study indicating benefit from CoQ10 (mean difference (MD) 22.41 points on the Kansas City Cardiomyopathy Questionnaire, 95% CI 12.18 to 32.64, 73 participants) and another indicating no benefit (MD −8.52 points, 95% CI −19.20 to 2.16, 66 participants).Conclusion Current evidence is insufficient to determine whether CoQ10 improves outcomes in HFpEF. Larger, high-quality and adequately powered RCTs using consistent diagnostic criteria are needed before CoQ10 can be recommended in clinical practice.PROSPERO registration number CRD420251027238.