Department of Internal Medicine, University of Illinois at Chicago/Advocate Christ Medical Center, Oak Lawn, Illinois, USA.
Department of Cardiovascular Diseases, Mayo Clinic, Rochester, USA.
Cochrane Database Syst Rev. 2021 Feb 3;(2)(2):CD008684. doi: 10.1002/14651858.CD008684.pub3.
Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria, and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases, including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in people with heart failure, and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels, and in preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to people with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials was conducted prior to the original version of this Cochrane Review, in 2014.
To review the safety and efficacy of coenzyme Q10 in heart failure.
We searched CENTRAL, MEDLINE, Embase, Web of Science, CINAHL Plus, and AMED on 16 October 2020; ClinicalTrials.gov on 16 July 2020, and the ISRCTN Registry on 11 November 2019. We applied no language restrictions.
We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in people with heart failure. When we identified cross-over studies, we considered data only from the first phase.
We used standard Cochrane methods, assessed study risk of bias using the Cochrane 'Risk of bias' tool, and GRADE methods to assess the quality of the evidence. For dichotomous data, we calculated the risk ratio (RR); for continuous data, the mean difference (MD), both with 95% confidence intervals (CI). Where appropriate data were available, we conducted meta-analysis. When meta-analysis was not possible, we wrote a narrative synthesis. We provided a PRISMA flow chart to show the flow of study selection.
We included eleven studies, with 1573 participants, comparing coenzyme Q10 to placebo or conventional therapy (control). In the majority of the studies, sample size was relatively small. There were important differences among studies in daily coenzyme Q10 dose, follow-up period, and the measures of treatment effect. All studies had unclear, or high risk of bias, or both, in one or more bias domains. We were only able to conduct meta-analysis for some of the outcomes. None of the included trials considered quality of life, measured on a validated scale, exercise variables (exercise haemodynamics), or cost-effectiveness. Coenzyme Q10 probably reduces the risk of all-cause mortality more than control (RR 0.58, 95% CI 0.35 to 0.95; 1 study, 420 participants; number needed to treat for an additional beneficial outcome (NNTB) 13.3; moderate-quality evidence). There was low-quality evidence of inconclusive results between the coenzyme Q10 and control groups for the risk of myocardial infarction (RR 1.62, 95% CI 0.27 to 9.59; 1 study, 420 participants), and stroke (RR 0.18, 95% CI 0.02 to 1.48; 1 study, 420 participants). Coenzyme Q10 probably reduces hospitalisation related to heart failure (RR 0.62, 95% CI 0.49 to 0.78; 2 studies, 1061 participants; NNTB 9.7; moderate-quality evidence). Very low-quality evidence suggests that coenzyme Q10 may improve the left ventricular ejection fraction (MD 1.77, 95% CI 0.09 to 3.44; 7 studies, 650 participants), but the results are inconclusive for exercise capacity (MD 48.23, 95% CI -24.75 to 121.20; 3 studies, 91 participants); and the risk of developing adverse events (RR 0.70, 95% CI 0.45 to 1.10; 2 studies, 568 participants). We downgraded the quality of the evidence mainly due to high risk of bias and imprecision.
AUTHORS' CONCLUSIONS: The included studies provide moderate-quality evidence that coenzyme Q10 probably reduces all-cause mortality and hospitalisation for heart failure. There is low-quality evidence of inconclusive results as to whether coenzyme Q10 has an effect on the risk of myocardial infarction, or stroke. Because of very low-quality evidence, it is very uncertain whether coenzyme Q10 has an effect on either left ventricular ejection fraction or exercise capacity. There is low-quality evidence that coenzyme Q10 may increase the risk of adverse effects, or have little to no difference. There is currently no convincing evidence to support or refute the use of coenzyme Q10 for heart failure. Future trials are needed to confirm our findings.
辅酶 Q10，又称泛醌，是一种非处方药营养补充剂。它是一种脂溶性分子，在线粒体中作为电子载体，并且是线粒体酶的辅酶。辅酶 Q10 缺乏可能与多种疾病有关，包括心力衰竭。心力衰竭的严重程度与辅酶 Q10 缺乏的严重程度相关。新出现的数据表明，心力衰竭患者体内的活性氧有害作用增加，而辅酶 Q10 可能通过其抗氧化活性有助于减轻这些毒性作用。辅酶 Q10 还可能在稳定心肌钙依赖性离子通道以及防止消耗对三磷酸腺苷 (ATP) 合成至关重要的代谢物方面发挥作用。尽管不是主要推荐的治疗方法，但辅酶 Q10 对心力衰竭患者可能有益。几项随机对照试验比较了辅酶 Q10 与其他治疗方式，但在 2014 年的 Cochrane 综述原始版本之前，没有对现有的随机试验进行系统评价。
综述辅酶 Q10 在心力衰竭中的安全性和疗效。
我们于 2020 年 10 月 16 日检索了 CENTRAL、MEDLINE、Embase、Web of Science、CINAHL Plus 和 AMED；于 2020 年 7 月 16 日检索了 ClinicalTrials.gov；于 2019 年 11 月 11 日检索了 ISRCTN 注册库。我们未对语言进行限制。
我们纳入了评估辅酶 Q10 对心力衰竭患者有益和有害影响的平行或交叉设计的随机对照试验。当我们发现交叉试验时，我们仅考虑了第一阶段的数据。
我们使用标准的 Cochrane 方法，使用 Cochrane“风险偏倚”工具评估研究的风险偏倚，并使用 GRADE 方法评估证据质量。对于二分类数据，我们计算了风险比 (RR)；对于连续数据，计算了均值差 (MD)，两者均带有 95%置信区间 (CI)。如果有适当的数据，我们进行了荟萃分析。当无法进行荟萃分析时，我们进行了叙述性综合。我们提供了 PRISMA 流程图，以显示研究选择的流程。
我们纳入了 11 项研究，共纳入 1573 名参与者，将辅酶 Q10 与安慰剂或常规治疗（对照组）进行比较。在大多数研究中，样本量相对较小。研究之间在辅酶 Q10 的每日剂量、随访期和治疗效果测量方面存在重要差异。所有研究在一个或多个偏倚领域都存在不明确或高风险的偏倚，或者两者兼而有之。我们只能对部分结果进行荟萃分析。纳入的试验均未考虑基于验证量表的生活质量、运动变量（运动血液动力学）或成本效益。辅酶 Q10 可能比对照组更能降低全因死亡率（RR 0.58，95%CI 0.35 至 0.95；1 项研究，420 名参与者；每治疗 13.3 例额外有益结果需要治疗 (NNTB)；中质量证据）。辅酶 Q10 与对照组之间在心肌梗死（RR 1.62，95%CI 0.27 至 9.59；1 项研究，420 名参与者）和中风（RR 0.18，95%CI 0.02 至 1.48；1 项研究，420 名参与者）风险方面的结果存在低质量证据，结果不确定。辅酶 Q10 可能降低与心力衰竭相关的住院率（RR 0.62，95%CI 0.49 至 0.78；2 项研究，1061 名参与者；NNTB 9.7；中质量证据）。非常低质量证据表明，辅酶 Q10 可能改善左心室射血分数（MD 1.77，95%CI 0.09 至 3.44；7 项研究，650 名参与者），但对运动能力的影响结果不确定（MD 48.23，95%CI -24.75 至 121.20；3 项研究，91 名参与者）；以及发生不良事件的风险（RR 0.70，95%CI 0.45 至 1.10；2 项研究，568 名参与者）。我们主要由于高风险偏倚和不精确而降低了证据的质量。
纳入的研究提供了中等质量的证据，表明辅酶 Q10 可能降低全因死亡率和心力衰竭住院率。辅酶 Q10 是否对心肌梗死或中风的风险有影响，结果存在低质量证据，不确定。由于非常低质量的证据，辅酶 Q10 对左心室射血分数或运动能力的影响仍不确定。辅酶 Q10 可能增加不良反应的风险，或几乎没有差异。目前没有令人信服的证据支持或反驳辅酶 Q10 用于心力衰竭。需要进一步的试验来证实我们的发现。
