DLM: Omega-3 Fatty Acids (2009-2010)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To investigate the effect of fish oil supplementation vs. placebo on recurrent ventricular arrhythmia in patients with implantable ventricular cardioverter defibrillators (ICD).

Inclusion Criteria:

Patients greater than 18 year of age with an ICD capable of recording intracardiac events and having at least one confirmed incident of ventricular tachycardia (VT) or ventricular fibrillation (VF) in the previous year.

 

Exclusion Criteria:

ICD for prophylactic reasons or as a bridge to cardiac transplantation, VT despite therapy, taking n-3 supplements in past eight months, intake of more than eight grams of n-3 fatty acids  per month (267mg per day) from fish or seafood, pregnant women, women of child-bearing age not using contraception, alcohol abuse or projected life span of less than one year.

Description of Study Protocol:

Recruitment

Patients recruited from 26 cardiology clinics in eight countries.

Design

Multicenter randomized controlled trial in which patients were randomly assigned to receive two grams fish oil (FO) capsules (containing 913mg n-3 as 464mg EPA and 335mg DFHA and 3,000ppm alpha-tocopherol ) or identical capsules containing  two grams high oleic acid safflower oil and 3,000ppm alpha tocopherol. Assignment using blocked stratification by clinic and beta-blocker use. Compliance was evaluated by return capsule count and serum cholesterol ester and serum fatty acid analysis obtained at baseline and at end of study. Fish oil intake was estimated by dietary recall every four months.

Blinding Used

Capsules were identical and both patients and researchers were blinded as to treatment.

Intervention

Two grams fish oil (FO) capsules (containing 913mg n-3 as 464mg EPA and 335mg DFHA and 3,000ppm alpha-tocopherol) or identical capsules containing  two grams high oleic acid safflower oil and 3,000ppm alpha tocopherol. Risks for arrhythmia at one year were calculated. 

Statistics

Heterogeneity evaluated using Q-statistic and I2 statistic and incorporated using Der Simonian and Laird random effects model. Mantel-Hanzel fixed effect model were used when heterogeneity was negligible. All comparisons were tested for two-tailed significance at the P<0.05 level of significance. 

Data Collection Summary:

Timing of Measurements

Median period of treatment was 356 days (range 14 to 379 days).

Dependent Variables

  • Primary endpoints: Sustained ICD intervention (shock or anti-tachycardia pacing for VT or VF) or death
  • Secondary endpoints: 
    • Cardiac death
    • ICD intervention for first event
    • True VT
    • VF
    • MI.

Independent Variables

FO vs. placebo.

Control Variables

Sex, ejection fraction, current smoking, NYHA class for dyspnea, valvular heart disease, prior MI, cardiomyopathy, VT as index arrhythmia, VF as index arrhythmia and use of anti-arrhythmic medications at baseline.

Description of Actual Data Sample:
  • Initial N: 546 enrolled and randomized to treatment; N=273 FO and N=277 placebo 
  • Attrition (final N): 244 FO and 248 placebo
  • Age: FO, 60.5±12.8 years; placebo, 62.4±11.4 years
  • BMI: FO, 26.98±4.04; placebo, 26.86±4.01
  • Location: Eight countries in UK and Europe.

 

 
Summary of Results:

 

 

Primary End Point

FO

N (%)

Placebo

N (%)

Hazard Ratio (95% CI)

P-value

ICD intervention or death

81 (30)

90 (33)

0.86 (0.64,1.16)

0.32

Secondary Endpoint

 

 

 

 

Death (all cause)

8 (3)

14 (5)

 

 

Cardiac death

6 (2)

13 (5)

 

 

ICD intervention for first event

 

75 (27)

 

31 (30)

 

0.89 (0.65, 1.22)

 

0.46

True VT

72 (26)

78 (29)

0.89 (0.64,1.22)

0.46

VF

3 (1)

3 (1)

 

 

MI

1 (0.4)

3 (1)

 

 

 

 

 

 

 

Time to First Event

 

 

 

 

  All Patients

81/273

90/273

0.86 (0.64, 1.16)

 

  VT as index

47/149

58/153

0.77 (0.52, 1,13)

 

  VF as index

8/41

9/43

0.79 (0.26, 2.37)

 

  Prior MI

47/162

61/170

0.76 (.52, 1.11)

 

  EF<30%

29/87

36/95

0.82 (0.5, 1.33)

 

  No Anti-arrhythmia medication

 

36/97

 

43/116

 

0.96 (0.59,1.57)

 

 

 

Author Conclusion:

No evidence of protective effect of FO n-3 fatty acids against ventricular arrhythmias in patients with ICDs.

Funding Source:
Reviewer Comments:
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? 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? Yes
  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? N/A
  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? Yes
  6.6. Were extra or unplanned treatments described? ???
  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? N/A
  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)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  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? No
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? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes