DM: Omega-3 Fatty Acids (2014)
Citation:
Holman RR, Paul S, Farmer A, Tucker L, Stratton IM, Neil HA, Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes Study Group. Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomized controlled trial. Diabetologia, 2009; 52 (1): 50-59.
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
The aim of the present study was to examine the impact of statin or mega-3 ethyl esters 90 (omega-3 ethyl esters) on estimated cardiovascular disease risk in community based type 2 diabetes subjects without known CVD and not taking lipid-lowering therapy.
Inclusion Criteria:
- Patients with type 2 diabetes for at least three months
- Aged 18 years or older
- No known CVD events
- Not taking lipid-lowering drugs.
Exclusion Criteria:
- Taking lipid-lowering therapy
- Triacylglycerol over 8.0mmol per L
- Impaired hepatic function [alanine aminotransferase (ALT) greater than two times the upper limit of normal]
- Uncontrolled diabetes (HbA1c over 10%)
- Uncontrolled hypertension (blood pressure persistently over 160/100mmHg)
- Elevated creatine kinase (more than three times the upper limit of normal).
Description of Study Protocol:
- Recruitment: Patients were recruited from primary care clinics and were participants of the AFORRD trial
- Design: A randomized controlled two-by-two factorial trial
- Blinding used: Patients and study staff were masked to the study medication group assignemnts.
Intervention
- A total of 800 eligible patients were randomized to double-blind study medication two weeks after their screening visit
- Computerized central randomization was used to allocate them in a two-by-two factorial manner to atorvastatin (Lipitor, 20mg per day) or matching placebo and, simultaneously, to omega-3 EE90 (Omacor, two grams per day) or matching placebo (olive oil, two grams per day)
- Omega-3 capsules contained 46% EPA and 38% DHA
- Lipid profiles were measured at entry and at four months, with CVD risks estimated using the UK Prospective Diabetes Study risk engine
- A central computer randomized 800 patients in 59 UK general practices to atorvastatin (N=401, 20mg per day) or placebo (N=399) and omega-3 EE90 (N=397, two grams per day) or placebo (N=403) in a concealed factorial manner.
Statistical Analysis
- The X2 and Wilcoxon tests were used for categorical and continuous variables respectively to compare between-group differences
- A 10-year CVD risk was estimated from age, duration of diagnosed diabetes, sex, self-reported ethnicity, smoking status, HbA1c, systolic BP and total cholesterol-to-HDL-C ratio, using the UKPDS risk engine
- Study medication interaction effects were analyzed using the general linear model.
Data Collection Summary:
Timing of Measurements
- Baseline measurements for HbA1c and lipid profile were conducted
- At four months, HbA1c and lipid profile were collected.
Dependent Variables
- HbA1c (measured by liquid chromatography)
- Total cholesterol
- HDL-cholesterol (HDL-C kit)
- LDL-cholesterol
- TG (colorimetric)
- Blood pressure.
Omega-3 supplementation.
Control Variables
All demographic variables.
Description of Actual Data Sample:
Initial N
- Total: 800
- Atorvastatin + omega-3: 200
- Atorvastatin + placebo: 201
- Omega-3 + placebo: 197
- Placebo + placebo: 202.
Attrition (Final N)
- Total: 732 (8.5% attrition)
- Atorvastatin + omega-3: 188
- Atorvastatin + placebo: 183
- Omega-3 + placebo: 183
- Placebo + placebo: 178.
Age
Mean age was 63.5±11.7 years and 57% were males (N=459 out of 800).Ethnicity
90.4% were white.Anthropometrics
Mean BMI was 30.8±6.2kg/m2 and was not different among groupsMean WC was 103±14cm and was not different among groups.
Summary of Results:
Key Findings
- Of 732 patients with four months of data, more allocated to atorvastatin (N=371), compared with placebo (N=361), achieved LDL-C of less than 2.6mmol per L (91% vs. 24%, P<0.001) and had estimated 10-year CVD risks of less than 20% (38% vs. 26%, P<0.001)
- No differences were noticed between Omega-3 and Placebo Groups for participants achieving triacyglycerol below 1.5mmol per L (65% vs. 60%, P=0.18) or estimated 10-year CVD risks below 20% (34% vs. 30%, P=0.18)
- There was a reduction in mean triacylglyceraol of 0.09mmol per L (5.6%, P=0.003) but no significant changes in LDL-C, 10-year CVD risk, total cholesterol, systolic or diastolic blood pressure of HbA1c.
Author Conclusion:
- Omega-3 has no impact on CVD risk factors
- Triglycerides levels do indicate some reduction after omega-3 supplementation levels, however other lipids labs show no change after omega-3 supplementation.
Funding Source:
Industry: |
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Reviewer Comments:
Quality Criteria Checklist: Primary Research
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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? | Yes | |
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? | N/A | |
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? | Yes | |
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)? | No | |
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? | Yes | |
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? | No | |
10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
10.2. | Was the study free from apparent conflict of interest? | Yes | |