Heart Failure

HF: CoEnzyme Q10 (2007)

Citation:

Baggio E, Gandini R, Plancher AC, Passeri M, Carmosino G. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Molec Aspects Med . 1994, 15 (Suppl): s287-s294.

 
Study Design:
Before-After Study
Class:
D - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To investigate the safety and the clinical efficacy of CoQ10 addition to the conventional therapy over  a 3-month period in a population with stable congestive heart failure of NYHA class II and III.
Inclusion Criteria:

Diagnosis of CHF for a minimum of 6 months documented by a recent electrocardiogram and chest X-ray

Doses of standard therapy constant over hte previous 3 months

 

Exclusion Criteria:

Valve disease with dignificant hemodymnamic distrubance, acute myocardial infaction iwthin the previous 3 months, angina, congenital heart disease, moderate or severe hypertension uncontrolled by therapy, cardiac revascularization with the past 3 months, cerebrovascular accident int he past 6 monts, history of seizures or severe reanl or helpatic disease. 

 

Description of Study Protocol:

Recruitment

Potentially elegible patients with signs and symptoms of CHF diagnosed for >6 months who were being seen by private and hospital cardiologists at 173 centers in Italy.   Diagnosis was documented by electrocardiogram and chest X-ray.   

Design

A before-after study in which a daily dosage of CoQ10 of either 50 mg (13.4 % of patients), 100 mg (78% of patients) or 150 mg (8.6% of patients) was given for 3 months to patients with a minimum of 6 month duration congestive heart failure.  At baseline and at 3 months,  patients were graded according to the NYHA functional class.  Measurements performed included blood pressure, heart rate, respiratory rate and blood sodium and potassium levels.  Two- to seven point scales were used for the assessment of clinical signa and symptoms.   The clinical assessments were: cyanosis (0-3), edema (0-3), pulmonary rales (0-4), enlargement ofthe liver area (0-3), jugular reflux (0-2), dyspnea (0-6), palpitations (0-3), insomnia (0-3), sweating (0-1), subjective arrhythmia (0-3), vertigo (0-3) and nocturia (0-3).  Preexisting adverse reactions were recorded at baseline.  Non-preexistent adverse reactions were recorded during the 3 months of treatment. 

Blinding used (if applicable)

None

Intervention (if applicable)

A daily dosage of CoQ10 of either 50 mg (13.4 % of patients), 100 mg (78% of patients) or 150 mg (8.6% of patients) was given for 3 months to all participants.

Statistical Analysis

Descriptive statistics (mean, range, standard deviation) were used for continuous variables(age, systolic and iastolic blood pressure).

Noncontinuous variables (e.g. patients with insommia) were expressed as percent and frequency. 

Statistical analysis for pre/post-treatment effect was preformed using ht e paired t test for continuous variable, Wilcoxon signed-rantk test for score (e.g. dyspnea), and chi-square test for frequency data. 

For all tests p = 0.05 was accepted as the significance level. 

The number of patients reporting adverse reactions was tabulated with ADE descriptions. 

Data Collection Summary:

Timing of Measurements

Meaurements were performed at baseline and at 3 months.

Dependent Variables

  • Variable 1:  NYHA functional class was used to grade patients
  • Variable 2:  Blood pressure, heart rate in the uspine and sitting position, respiratory rate, serum sodium and serum potassium were measured.
  • Variable 3: Two- to seven point scales were used for the assessment of clinical signs and symptoms.   The clinical assessments were: cyanosis (0-3), edema (0-3), pulmonary rales (0-4), enlargement ofthe liver area (0-3), jugular reflux (0-2), dyspnea (0-6), palpitations (0-3), insomnia (0-3), sweating (0-1), subjective arrhythmia (0-3), vertigo (0-3) and nocturia (0-3). 
  • Independent Variables

CoQ10

Control Variables

NYHA functional class, blood pressure, heart rate, respiratory rate, biochemical meaurements and clinical signs and symptoms.

Description of Actual Data Sample:

Initial N: (e.g., 731 (298 males, 433 females))

2664

Attrition (final N):

2359 (1181 male and 1178 female)

150 were excluded due to protocol violations of inclusion criteria, 150 not analyzed because of poor compliance. 

Age:

Mean of 68.5 years (range 41-91)

Ethnicity:

Living in Italy

Other relevant demographics:

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

All had been diagnosed with CHF for >6 months and had been on a constant dose of therapy for the previous 3 months.  Patients who had valve disease with significant hemodymnamic disturbance, acute myocardial infarction within the previous 3 months, angina, congenital heart disease, moderate or severe hypertension uncontrolled by therapy, cardiac revascularization with the past 3 months, cerebrovascular accident int he past 6 monts, history of seizures or severe renal or hepatic disease were excluded. 

Location:

Private doctor's offices and hospital clinics in Italy

Summary of Results:

 

Variables

Treatmintervals Controlent Group

Measures and confidence intervals

Control group

Measures and confidence intervals

Statistical Significance of Group Difference

Dependent Variable 1: Blood Pressure

supine systolic

149.4 ± 18

143.8 ± 14.9

p <0.05

sitting diastolic 

83.7 ± 7.6

82.0 ± 6.8

p <0.05

supine systolic

147.8 ± 18.7

143.4 ± 15.4

p <0.05

sitting diastolic   

84.2 ± 7.6

82.6 ± 7.1

p <0.05

Dep var 2: Heart rate

supine

78.4 ± 9.6

75.1 ± 8.2

p <0.05

sitting

80.3 ± 9.5

77.9 ± 8.1

p <0.05

Respiratory rate

Serum sodium(mmolSymptombaseline Improved/l)

Serum potassium (mmol/l)

21.2 ± 3.9

140.9 ± 5.2

 

4.2 ± 0.4

 

 

20.6 ± 3.5

140.3 ± 5.7

 

4.2 ± 0.4

 

 

p <0.05

NS

 

NS

 

Other Findings

Symptom n at baseline Improved 1 point (%) P value
Cyanosis 675 78.67 <0.01
Edema 1764 78.06 <0.01
Pulmonary rales 1752 77.85 <0.01
Enlarged liver area 1285 49.26 <0.01
Jugular reflux 713 71.81 <0.01
Dyspnea 2163 52.75 <0.01
Palpitations 1903 75.46 <0.01
Sweating 1044 79.79 <0.01
Subjective arrhythmia 1143 63.43 <0.01
Insomnia 1597 62.87 <0.01
Dizziness 1282 73.13 <0.01
Nocturia 1541 53.67 <0.01

184 patients changed from NYHA class III to class II, 69 increased to the lowest class, 35 increased from class II to class III, 142 did not change class and 1538 decreased their score. 

Seven patients had to discontinue CoQ10 because of disabling symptomatology (maculopapular rash or nausea and epigastric pain).   Other side effects reported were dizziness, photophobia, and irritability.  Dosage of the drug appeared to resolve the problem

Author Conclusion:
The preliminary results indicate that CoQ10 adjunctive therapy induces clinical improvement in patients with mild to moderate heart failure.
Funding Source:
University/Hospital: V. Buzzi Hospital (Italy), General Hospital (Reggio Emilia), University Parma
Reviewer Comments:

A large study in which a large percentage showed improved in symptoms of CHF.  Unfortunately the paper did not document how the 173 different centers were equally assessing those symptoms. 

 

 

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? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? N/A
  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? N/A
  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? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  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.) N/A
  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? Yes
  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? ???
  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? N/A
  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? ???
  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? ???
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? No
  9.1. Is there a discussion of findings? No
  9.2. Are biases and study limitations identified and discussed? No
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? ???