Heart Failure

Coenzyme Q10 Supplementation

Citation:

Berman M, Erman A, Ben-Gal T, Dvir D, Georghiou GP, Stamler A, Vered Y, Vidne BA, Aravot D.  Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study.  Clin Cardiol. 2004, 27: 295-299.

 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To assess the effect of CoQ10 on patients with end-stage heart failure and to determine whether CoQ10 can improve the pharmacologic bridge to heart transplantation.
Inclusion Criteria:

End-stage heart failure

Class 3 or 4 NYHA

Left ventricular ejection fraction <25%

Cardiopulmonary exercise test (CARPET) with maximal O2 <14 ml/kg/h

Evident symptoms of heart failure such as nocturia, dyspnea, and paroxysmal nocturnal dyspnea.

Exclusion Criteria:

Patients with United Network for Organ Sharing (UNOS) Status One

Moderate renal failure with creatinine levels >2.5 mg/dl

Description of Study Protocol:

Recruitment

Candidates for heart transplant at the Rabin Medical Center, Petah-Tikva, Israel

 

Design

RCT 

 

Blinding used (if applicable)

double-blind

 

Intervention (if applicable)

60 mg/day U-CoQ10 or corn flour-based placebo for 3 months.  U-CoQ10 is ultrasome coenzyme Q10, a novel, patented technology for improving the oral bioavailability of lipophilic nutriceutical and pharmaceuticals.  U-CoQ10 is a spray-dried, lipid-based, powdered formulation of CoQ10 in capsule form. 

 

Statistical Analysis

Statistical analysis was performed with the BMDP statistical software as follows: repeated measure for time 0 and time 3 months with one nested variable (two groups) performed for all variables, and analysis of variance with data screening.  Catagorical variables are described as frequencies and percentages, and continuous variables as the means (standard deviation [SD]).  A p value of <0.05 was considered statistically significant. 

 

Data Collection Summary:

Timing of Measurements

Baseline and 3 months

 

Dependent Variables

  • Variable 1:  Quality of life and severity of subjective heart failure symptoms were determined by a detailed anamnesis using a survey based in part on the Minnesota Living with Heart Failure Questionnaire.
  • Variable 2:  Echocardiography as performed to assess aortic diameter, left atrium diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, posterior wall thickness, interventricular septal width, and shortening fraction. 
  • Variable 3: Six minute walk test

Blood levels of atrial natriuretic factor (ANF, tumor necrosis factor (TNF) alpha and CoQ10.  Blood was drawn after an 8 hour fast. 

Coenzyme Q10 was determined by the method described by Grossi.  Compliance was also determined by a count of the remaining capsules by pharmacy personnel.

The ANF was determined by radioimmunassay kit.  One ml of blood was drawn into test tubes containing 50 ul of 0.01M solution of K3EDTA to which aprotinin 500kIU/ml was added.  The plasma was extracted on C-18 columns (200 mg) using 1% trifluoroacetic acid and 60% acetonitrite in 1% trifluoroacetic acid as solvents.  The extract was evaporated to dryness.  One ml of phosphate buffer was added, and the tubes were kept frozen at -200 until assay. 

Plasma TNF-alpha determination was performed using a solid phase, two-sided chemiluminescent enzyme immunometric assay kit.  The plasma samples were kept at -20o until assay.

       

  • Independent Variables

CoQ10

Control Variables

 

Description of Actual Data Sample:

Initial N:  32 (28 men, 4 women)

Attrition (final N):

27.  Five failed to complete the study because of death, need for heart transplantation, drug-induced intestinal upset, inconvenient travel connections and lack of compliance (one patient each)

Age:

40-67 years, mean 54.6

Ethnicity:

Not stated

Other relevant demographics:

Anthropometrics (e.g., were groups same or different on important measures)

Twenty five of the patients had ischemic cardiomyopathy and 7 had dilated cardiomyopathy.  All had been stable for at least 1 month.  The waiting time a heart transplant ranged from 2 to 67 months (mean 26 months).  All patients were receiving some combination of the following: diuretics (76%0, antiarrhythmic agents (45%), beta blockers (52%), digitalis (85%), afterload reducing agents (65%), angiotensin-converting enzyme inhibitors (45%) and anticoagulants (19%). 

Location:

Petah-Tikva, Israel

 

Summary of Results:

 

Variables

Treatment Group

Measures and confidence intervals

Control group

Measures and confidence intervals

Statistical Significance of Group Difference

nocturia frequency 1.7 to 1.46 times/n

2.1 to 2.63 times/n

p=<0.01

severity of fatigue (median score)

2.4 to 1.96

2.9 to 3.54

p=<0.001

severity of dyspnea (median score)

2.9 to 2.1

3.68 to 3.5

p= 0.04

NYHA class (medium score)

3.1 to 2.4

3.68 to 3.6

p=0.01

Echocardiography

no change no change

NS

6 minute walk 269.5 to 382.2 min 254 to 177 min

p=<0.0001

ANF (pg/ml)

231 ± 22.5 baseline 185.2 ± 21.6 end

307.33 ± 29.4 base 260.22 ± 23.8 end

NS

TNF (pg/ml)

8.25 ± 2.3 base 10.47 ± 3.1 end

15.57 ± 2.9 base 16.1 ± 3.5 end

NS

 

Other Findings

One patient withdrew from the study due to drug-induced intestinal upset.  This was the only side effect reported.

 

Author Conclusion:
The heart transplant candidates who took CoQ10 showed significant improvement in functional status, clinical symptoms, and quality of life.  There were no objective changes in echo measurements or TNF and ANF blood levels
Funding Source:
University/Hospital: University of Chicago
Reviewer Comments:

Small group of patients who were in end-stage heart failure

Coenzyme Q10 blood levels were analyzed but the results not given

Placebo group had a higher level of TNF at baseline than the treated group.

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? Yes
3. Were study groups comparable? Yes
  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? Yes
  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? No
  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%.) No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? ???
  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? No
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? No
  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? ???
  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? ???
  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? ???
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? ???
  7.5. Was the measurement of effect at an appropriate level of precision? ???
  7.6. Were other factors accounted for (measured) that could affect outcomes? N/A
  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)? N/A
  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? No
  10.2. Was the study free from apparent conflict of interest? ???