Madmani Mohammed E, Yusuf Solaiman Ahmad, Tamr Agha Khalil, Madmani Yasser, Shahrour Yasser, Essali Adib, Kadro Waleed
Department of internal medicine, Case Western Reserve University/MetroHealth Medical Center Campus, Cleveland, OH, USA.
Cochrane Database Syst Rev. 2014 Jun 2(6):CD008684. doi: 10.1002/14651858.CD008684.pub2.
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 patients 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 preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to patients with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials has been conducted.
To review the safety and efficacy of coenzyme Q10 in heart failure.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE OVID (1950 to January Week 3 2013) and EMBASE OVID (1980 to 2013 Week 03) on 24 January 2013; Web of Science with Conference Proceedings (1970 to January 2013) and CINAHL Plus (1981 to January 2013) on 25 January 2013; and AMED (Allied and Complementary Medicine) (1985 to January 2013) on 28 January 2013. 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 patients with heart failure. When cross-over studies were identified, we considered data only from the first phase.
Two authors independently extracted data from the included studies onto a pre-designed data extraction form. We then entered the data into Review Manager 5.2 for analysis. We assessed study risk of bias using the Cochrane 'Risk of bias' tool. For dichotomous data, we calculated the risk ratio and for continuous data the mean difference (MD). Where appropriate data were available, we performed meta-analysis. For this review we prioritised data from pooled analyses only. Where meta-analysis was not possible, we wrote a narrative synthesis. We provided a QUOROM flow chart to show the flow of papers.
We included seven studies with 914 participants comparing conenzyme Q10 versus placebo. There were no data on clinical events from published randomised trials. The included studies had small sample sizes. Meta-analysis was only possible for a few physiological measures and there was substantial heterogeneity.Only one study reported on total mortality, major cardiovascular events and hospitalisation. Five trials reported on the New York Heart Association (NYHA) classification of clinical status, but it was impossible to pool data due to heterogeneity. None of the included trials considered quality of life, exercise variables, adverse events or cost-effectiveness as outcome measures. Pooled analysis suggests that the use of coenzyme Q10 has no clear effect on left ventricular ejection fraction (MD -2.26; 95% confidence interval (CI) -15.49 to 10.97, n = 60) or exercise capacity (MD 12.79; 95% CI -140.12 to 165.70, n = 85). Pooled data did indicate that supplementation increased blood levels of coenzyme Q10 (MD 1.46; 95% CI 1.19 to 1.72, n = 112). However, there are only a small number of small studies with a risk of bias, so these results should be interpreted with caution.
AUTHORS' CONCLUSIONS: No conclusions can be drawn on the benefits or harms of coenzyme Q10 in heart failure at this time as trials published to date lack information on clinically relevant endpoints. Furthermore, the existing data are derived from small, heterogeneous trials that concentrate on physiological measures: their results are inconclusive. Until further evidence emerges to support the use of coenzyme Q10 in heart failure, there might be a need to re-evaluate whether further trials testing coenzyme Q10 in heart failure are desirable.
辅酶Q10,即泛醌,是一种非处方营养补充剂。它是一种脂溶性分子,在线粒体中作为电子载体,并作为线粒体酶的辅酶。辅酶Q10缺乏可能与多种疾病相关,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,心力衰竭患者体内活性氧物质的有害作用增强,而辅酶Q10因其抗氧化活性可能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三磷酸腺苷(ATP)合成所必需的代谢物消耗方面发挥作用。辅酶Q10虽然不是主要推荐的治疗方法,但可能对心力衰竭患者有益。已有多项随机对照试验将辅酶Q10与其他治疗方式进行了比较,但尚未对现有随机试验进行系统评价。
评价辅酶Q10治疗心力衰竭的安全性和有效性。
我们于2013年1月24日检索了Cochrane对照试验中心注册库(CENTRAL)(2012年第12期);MEDLINE OVID(1950年至2013年1月第3周)和EMBASE OVID(1980年至2013年第3周);于2013年1月25日检索了科学引文索引会议论文数据库(1970年至2013年1月)和护理学与健康领域数据库(CINAHL Plus)(1981年至2013年1月);于2013年1月28日检索了联合与补充医学数据库(AMED)(1985年至2013年1月)。我们未设语言限制。
我们纳入了平行设计或交叉设计的随机对照试验,这些试验评估了辅酶Q10对心力衰竭患者的有益和有害影响。当识别出交叉研究时,我们仅考虑第一阶段的数据。
两位作者独立地从纳入的研究中提取数据,录入预先设计的数据提取表。然后我们将数据录入Review Manager 5.2进行分析。我们使用Cochrane“偏倚风险”工具评估研究的偏倚风险。对于二分法数据,我们计算风险比;对于连续数据,我们计算平均差(MD)。在有合适数据的情况下,我们进行荟萃分析。对于本综述,我们仅优先考虑汇总分析的数据。若无法进行荟萃分析,我们撰写叙述性综述。我们提供了QUOROM流程图以展示论文的流程。
我们纳入了7项研究,共914名参与者,比较了辅酶Q10与安慰剂。已发表的随机试验中没有关于临床事件的数据。纳入的研究样本量较小。仅对少数生理指标进行了荟萃分析,且存在显著异质性。仅有一项研究报告了总死亡率、主要心血管事件和住院情况。5项试验报告了纽约心脏协会(NYHA)临床状况分级,但由于异质性无法汇总数据。纳入的试验均未将生活质量、运动变量、不良事件或成本效益作为结局指标。汇总分析表明,使用辅酶Q10对左心室射血分数(MD -2.26;95%置信区间(CI)-15.49至10.97,n = 60)或运动能力(MD 12.79;95% CI -140.12至165.70,n = 85)无明显影响。汇总数据确实表明补充辅酶Q10可提高血液中辅酶Q10的水平(MD 1.46;95% CI 1.19至1.72,n = 112)。然而,仅有少数小型研究且存在偏倚风险,因此这些结果应谨慎解读。
目前无法就辅酶Q10对心力衰竭的益处或危害得出结论,因为迄今发表的试验缺乏关于临床相关终点的信息。此外,现有数据来自小型、异质性试验,且集中于生理指标:其结果尚无定论。在有进一步证据支持在心力衰竭中使用辅酶Q10之前,可能需要重新评估是否有必要进一步开展在心力衰竭中测试辅酶Q10的试验。