Coenzyme Q10 Supplementation
NYHA class III or IV with ejection fractions <40% documented by radionuclide ventriculography.
Maximal oxygen consumption <17.0 mL/kg of body weight per minute or < 50% of the predicted value.
Unchanged medical regimen for at least 1 month.
Previous use of coenzyme Q10.
Recruitment: Not stated
Design: Randomized, double-blind, placebo-controlled trial
Blinding used: All patients and study personnel were blinded to study group assignment until all data were final.
Intervention: 200 mg of coenzyme Q10 per day or placebo
Statistical Analysis
The change in values of primary and secondary end points were compared by using an unpaired Student t-test. All values are given as the mean ± SD. For significance, a P value less than 0.05 was required. The study was planned to have 80% power to detect a difference of 2.8 mL/kg per minute in the peak oxygen consumption, with a P value of 0.05. This assumed a mean oxygen consumption of 13.0 ± 4.0 mL/kg per minute. StatMost, version 3.5 was used for all statistical analyses.
Timing of Measurements
Baseline and 6 months after treatment
Dependent Variables
- Variable 1: Maximal oxygen consumption was assessed by a graded symptom-limited cardiopulmonary exercise test using the Naughton protocol. The test was performed by the same operator and was repeated until the maximum oxygen consumption measures o two consecutive test results were within 15% of each other. The final test was considered to be the baseline test with which to assess change during therapy.
- Variable 2: Change in ejection fraction was determined by radionuclide ventriculography using standard techniques.
- Variable 3 Serum concentration of coenzyme Q10 was determined by coupled-column liquid chromatography with coulometric and ultraviolet detection.
Independent Variables
- Coenzyme Q10
Initial N: 55 males and females
Attrition (final N): 46 (39 men and 7 women). Five patients in the coenzyme Q10 and 4 in the placebo did not finish. One patient in the placebo group died of progressive heart failure, and 2 patients in the coenzyme Q10 died of myocardial infarction and sudden death, respectively. Four patients did not complete the study because of conditions that prevented them from exercising (esophageal cancer, uncontrolled ventricular tachycardia, foot amputation, and pulmonary edema. One patient int eh coenzyme Q10 group withdrew from the study and one patient was withdrawn because of error in enrollment criteria.
Age: mean age was 64 years
Ethnicity: unknown
Other relevant demographics:
Anthropometrics (e.g., were groups same or different on important measures)
Twenty seven patients had known ischemic heart disease. Forty tow patents were NYHA class III and four were class IV. All were receiving digoxin and angiotensin-converting enzyme inhibitors or other vasodilators. Eighteen patients in each group were receiving B-blockers, and 22 patients in each group were receiving diuretics.
Location: Baltimore, MD
Treatment Group Measures and Control Group Measures
|
Variables |
Treatment Group Measures and confidence intervals |
Control group Measures and confidence intervals |
Statistical Significance of Group Difference |
|
Max O2 consumption (mL/kg/min) |
Mean, CI. +2.1 ± 3.4 (95% CI, -1.25 to 1.68)
|
Mean, CI. -0.49 ± 2.4 (CI, -1.54 to 0.55) |
Stat signif difference between groups NS |
|
Ejection fraction (%) |
-0.3 ± 8 (CI, -3.7 to 3.1) |
-0.2 ± 8.6 (CI, -4.0 to 3.6) |
NS |
|
Serum coenz Q10 (Ug/mL) |
0.95 ± 0.62 to 2.2 ± 1.2 |
0.92 ± 0.34 to 0.96 ± 0.45 |
P = <0.001 |
Other Findings
Exercise duration did not change significantly between groups (8.5 ± 3.2 minutes before treatment and 9.1 ± 3.4 minutes after treatment in the coenzyme Q10 group and 7.7 ± 3.2 minutes before treatment and 7.5 ± 2.9 minutes after treatment in the placebo group)
Mean left ventricular ejection fraction was 27% before and after treatment in the coenzyme Q10 group and 30% before and after treatment in the placebo group. Right ventricular ejection fraction was 35% ± 13 before treatment and 35% ± 11 after treatment in the before and after treatment while the placebo group decreased from 39% ±14 at start of treatment to 37% ± 8 after treatment.
One patient in each group had improved symptoms as indicated by the NYHA classification. Almost three quarters of the patients classified themselves as neigher improved nor worse after 6 months of treatment (18 on placebo and 16 on coenzyme Q10. Six patients in the coenzyme Q10 believed that their symptoms had improved even minimally and believed that symptoms had deteriorated. Two patients in the placebo group reported improvement in symptoms and 3 patients reported increased severity of symptoms.
No adverse reactions were attributed to the study drug, and not gastrointestinal side effects occurred.
| Government: | NIA | ||
| Not-for-profit |
|
Small number of subjects.
Recruitment not described.
|
Quality Criteria Checklist: Primary Research
|
|||
| Relevance Questions | |||
| 1. | Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) | Yes | |
| 2. | Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? | Yes | |
| 3. | Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? | Yes | |
| 4. | Is the intervention or procedure feasible? (NA for some epidemiological studies) | Yes | |
| Validity Questions | |||
| 1. | Was the research question clearly stated? | Yes | |
| 1.1. | Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? | Yes | |
| 1.2. | Was (were) the outcome(s) [dependent variable(s)] clearly indicated? | Yes | |
| 1.3. | Were the target population and setting specified? | Yes | |
| 2. | Was the selection of study subjects/patients free from bias? | Yes | |
| 2.1. | Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? | Yes | |
| 2.2. | Were criteria applied equally to all study groups? | Yes | |
| 2.3. | Were health, demographics, and other characteristics of subjects described? | Yes | |
| 2.4. | Were the subjects/patients a representative sample of the relevant population? | ??? | |
| 3. | Were study groups comparable? | ??? | |
| 3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | Yes | |
| 3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | ??? | |
| 3.3. | Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) | Yes | |
| 3.4. | If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? | N/A | |
| 3.5. | If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) | N/A | |
| 3.6. | If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? | N/A | |
| 4. | Was method of handling withdrawals described? | Yes | |
| 4.1. | Were follow-up methods described and the same for all groups? | Yes | |
| 4.2. | Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) | Yes | |
| 4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | Yes | |
| 4.4. | Were reasons for withdrawals similar across groups? | No | |
| 4.5. | If diagnostic test, was decision to perform reference test not dependent on results of test under study? | N/A | |
| 5. | Was blinding used to prevent introduction of bias? | Yes | |
| 5.1. | In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? | Yes | |
| 5.2. | Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) | Yes | |
| 5.3. | In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? | N/A | |
| 5.4. | In case control study, was case definition explicit and case ascertainment not influenced by exposure status? | N/A | |
| 5.5. | In diagnostic study, were test results blinded to patient history and other test results? | N/A | |
| 6. | Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? | Yes | |
| 6.1. | In RCT or other intervention trial, were protocols described for all regimens studied? | Yes | |
| 6.2. | In observational study, were interventions, study settings, and clinicians/provider described? | N/A | |
| 6.3. | Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? | Yes | |
| 6.4. | Was the amount of exposure and, if relevant, subject/patient compliance measured? | Yes | |
| 6.5. | Were co-interventions (e.g., ancillary treatments, other therapies) described? | N/A | |
| 6.6. | Were extra or unplanned treatments described? | N/A | |
| 6.7. | Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? | Yes | |
| 6.8. | In diagnostic study, were details of test administration and replication sufficient? | N/A | |
| 7. | Were outcomes clearly defined and the measurements valid and reliable? | Yes | |
| 7.1. | Were primary and secondary endpoints described and relevant to the question? | Yes | |
| 7.2. | Were nutrition measures appropriate to question and outcomes of concern? | Yes | |
| 7.3. | Was the period of follow-up long enough for important outcome(s) to occur? | Yes | |
| 7.4. | Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? | Yes | |
| 7.5. | Was the measurement of effect at an appropriate level of precision? | Yes | |
| 7.6. | Were other factors accounted for (measured) that could affect outcomes? | Yes | |
| 7.7. | Were the measurements conducted consistently across groups? | Yes | |
| 8. | Was the statistical analysis appropriate for the study design and type of outcome indicators? | Yes | |
| 8.1. | Were statistical analyses adequately described and the results reported appropriately? | Yes | |
| 8.2. | Were correct statistical tests used and assumptions of test not violated? | Yes | |
| 8.3. | Were statistics reported with levels of significance and/or confidence intervals? | Yes | |
| 8.4. | Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? | N/A | |
| 8.5. | Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? | No | |
| 8.6. | Was clinical significance as well as statistical significance reported? | Yes | |
| 8.7. | If negative findings, was a power calculation reported to address type 2 error? | N/A | |
| 9. | Are conclusions supported by results with biases and limitations taken into consideration? | Yes | |
| 9.1. | Is there a discussion of findings? | Yes | |
| 9.2. | Are biases and study limitations identified and discussed? | Yes | |
| 10. | Is bias due to study's funding or sponsorship unlikely? | ??? | |
| 10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
| 10.2. | Was the study free from apparent conflict of interest? | ??? | |