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Coenzyme Q10 to manage chronic heart failure with a reduced ejection fraction: a systematic review and economic evaluation

Lindsay Claxton, Mark Simmonds, Lucy Beresford, Richard Cubbon, Mark Dayer, Stephen S Gottlieb, Nick Hartshorne-Evans, Bruce Kilroy, Alexis Llewellyn, Claire Rothery, Sahar Sharif, Jayne F Tierney, Klaus K Witte, Kath Wright, Lesley A Stewart
Health Technology Assessment 2022 26(4):1-128

Bibliography

PubMed
PMID 35076012
DOI
10.3310/KVOU6959
Funding
Funded by the UK National Institute for Health Research Health Technology Assessment programme (project 17/12/02).
Competing interests
The report states that Richard Cubbon and Klaus K Witte contributed to the West Yorkshire database; Mark Dayer reported personal fees from Biotronik UK outside the submitted work; Stephen S Gottlieb and Klaus K Witte were principal investigators in one included trial.

Study snapshot

DesignSystematic review, meta-analysis and health economic evaluation
ModelSystematic review of randomized trials of CoQ10 plus standard care versus standard care alone in chronic heart failure with reduced ejection fraction, followed by UK cost-effectiveness modeling.
Sample26 trials; 2,250 participants.
InterventionCoQ10 plus standard heart-failure care versus standard care/placebo across randomized trials; HFpEF-only trials were excluded.
DurationVariable across included trials; literature searched through March 2020.
EndpointsAll-cause mortality; Heart-failure hospitalization; Functional outcomes; Adverse events; Potential statin interaction; Cost-effectiveness; Quality-adjusted life-years

What the study showed, in plain terms

This NIHR health-technology assessment focused specifically on HFrEF and included 26 trials with 2,250 participants, while also examining whether the evidence was strong enough to justify routine NHS prescribing.

The meta-analysis suggested a possible reduction in all-cause mortality (RR 0.68, 95% CI 0.45 to 1.03), but the confidence interval crossed 1. Short-term functional outcomes were more modest or unclear, and there was no signal of increased adverse events.

The authors judged CoQ10 potentially cost-effective if the treatment effect is real, but emphasized concerns about risk of bias, unusually large mortality estimates, manufacturer support in some underlying trials and limited applicability to a typical modern UK HFrEF population. They recommended a new independent adequately powered RCT.

Key findings

All-cause mortality: 7 trials/1,371 participants; RR 0.68, 95% CI 0.45 to 1.03—suggestive but not conventionally statistically significant.

Short-term functional outcomes were modest or uncertain across the evidence base.

No clear increase in adverse events was identified.

Meta-regression found no evidence that statin use modified treatment effect.

The economic model suggested favorable cost-effectiveness under its base-case assumptions, but those assumptions depend on uncertain clinical-effect estimates.

What this study can and cannot tell us

Many included trials were poorly reported and had high or unclear risk of bias.

A planned individual-participant-data meta-analysis was not feasible because sufficient trial-level data could not be obtained, so synthesis relied mainly on aggregate published data.

Several underlying trials reported support from CoQ10 manufacturers, and the authors questioned the plausibility and robustness of the large mortality effects.

The evidence base may not generalize cleanly to a contemporary UK HFrEF population receiving current guideline-directed therapy.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology