Coenzyme Q10 for heart failure.

BACKGROUND: 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. OBJECTIVES: To review the safety and efficacy of coenzyme Q10 in heart failure. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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.

Pacing for drug-refractory or drug-intolerant hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic disease with an autosomal-dominant inheritance for which negative inotropes are the most widely used initial therapies. Observational studies and small randomised trials have suggested symptomatic and functional benefits using pacing and several theories have been put forward to explain why. Pacing, although not the primary treatment for HCM, could be beneficial to patients with relative or absolute contraindications to surgery or alcohol ablation. Several randomised controlled trials comparing pacing to other therapeutic modalities have been conducted but no Cochrane-style systematic review has been done. OBJECTIVES: To assess the effects of pacing in drug-refractory or drug-intolerant hypertrophic cardiomyopathy patients. SEARCH METHODS: We searched the following on the 14/4/2010: CENTRAL (The Cochrane Library 2010, Issue 1), MEDLINE OVID (from 1950 onwards ), EMBASE OVID (from 1980 onwards ), Web of Science with Conference Proceedings (from 1970 onwards). No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials of either parallel or crossover design that assess the beneficial and harmful effects of pacing for hypertrophic cardiomyopathy were included. When crossover studies were identified, we considered data only from the first phase. DATA COLLECTION AND ANALYSIS: Data from included studies were extracted onto a pre-formed data extraction paper by two authors independently. Data was then entered into Review Manager 5.1 for analysis. Risk of bias was assessed using the guidance provided in the Cochrane Handbook. For dichotomous data, relative risk was calculated; and for continuous data, the mean differences were calculated. Where appropriate data were available, meta-analysis was performed. Where meta-analysis was not possible, a narrative synthesis was written. A QUROUM flow chart was provided to show the flow of papers. MAIN RESULTS: Five studies (reported in 10 papers) were identified. However, three of the five studies provided un-usable data. Thus the data from only two studies (reported in seven papers) with 105 participants were included for this review. There was insufficient data to compare results on all-cause mortality, cost effectiveness, exercise capacity, Quality of life and Peak O2 consumption.When comparing active pacing versus placebo pacing on exercise capacity, one study showed that exercise time decreased from (13.1 ± 4.4) minutes to (12.6 ± 4.3) minutes in the placebo group and increased from (12.1 ± 5.6) minutes to (12.9 ± 4.2) minutes in the treatment group (MD 0.30; 95% CI -1.54 to 2.14). Statistically significant data from the same study showed that left ventricular outflow tract obstruction decreased from (71 ± 32) mm Hg to (52 ± 34) mm Hg in the placebo group and from (70 ± 24) mm Hg to (33 ± 27) mm Hg in the active pacing group (MD -19.00; 95% CI -32.29 to -5.71). This study was also able to show that New York Heart Association (NYHA) functional class decreased from (2.5 ± 0.5) to (2.2 ± 0.6) in the inactive pacing group and decreased from (2.6 ± 0.5) to (1.7 ± 0.7) in the placebo group (MD -0.50; 95% CI -0.78 to -0.22).When comparing active pacing versus trancoronary ablation of septal hypertrophy (TASH), data from one study showed that NYHA functional class decreased from (3.2 ± 0.7) to (1.5 ± 0.5) in the TASH group and decreased from (3.0 ± 0.1) to (1.9 ± 0.6) in the pacemaker group. This study also showed that LV wall thickness remained unchanged in the active pacing group compared to reduction from (22 ± 4) mm to (17 ± 3) mm in the TASH group (MD 0.60; 95% CI -5.65 to 6.85) and that LV outflow tract obstruction decreased from (80 ± 35.5) mm Hg in the TASH group to (49.3 ± 37.7) mm Hg in the pacemaker group. AUTHORS' CONCLUSIONS: Trials published to date lack information on clinically relevant end-points. Existing data is derived from small trials at high risk of bias, which concentrate on physiological measures. Their results are inconclusive. Further large and high quality trials with more appropriate outcomes are warranted.