AlphaOmega ‐ EPA+DHA 2010

Methods	RCT, (EPA + DHA vs MUFA), 40 months Summary risk of bias: low
Participants	60‐80 year‐olds with previous MI N: 1192 EPA/DHA intervention, 1236 control (1212 ALA + EPA/DHA intervention group) Level of risk for CVD: high Men: 78.1% intervention, 78.7% control Mean age in years (SD): 69.1 (5.6) intervention, 68.9 (5.6) control Age range: 60‐80 years Smokers: 16.8%, intervention, 18% control Hypertension: unclear Medications taken by at least 50% of those in the control group: lipid‐lowering medication, antihypertensives, antithrombotics Medications taken by 20%‐49% of those in the control group: not reported Medications taken by some, but less than 20% of the control group: antiarrythmic drugs, antidiabetic drugs Location: the Netherlands Ethnicty: not reported
Interventions	Type: supplementary margarine Comparison 1: EPA + DHA vs MUFA Intervention: 20 g of enriched margarine per day incorporating 400 mg EPA‐DHA (240 mg EPA and 160 mg DHA). Dose: average achieved 376 mg/d EPA + DHA Control: 20 g of margarine per day. No additional n‐3 PUFAs. Identical margarine (oleic acid) placebo Compliance: unused margarine tubs were returned; daily intakes of margarine and n‐3 fatty acids were calculated on the basis of the amount unused. Adherence was measured by levels of fatty acids in plasma cholesteryl esters, margarine and questionnaires. 90.5% of patients adhered to the protocol. Length of intervention: 40 months
Outcomes	Main study outcome: cardiovascular disease events   Dropouts: 95 died, 119 discontinued intervention, 93 died, 93 discontinued control Available outcomes: deaths, MI, cardiovascular events, ventricular arrhythmia, incident cardiovascular disease Response to contact: yes (data provided)
Notes	The study has three intervention arms (ALA margarine, EPA/DHA margarine, mixture of the two interventions). This table represents theEPA/DHA only intervention. Outcome data is used for the EPA/DHA group where available or for the combined (EPA/DHA arm, EPA/DHA + ALA arm) Study funding: Netherlands Heart Foundation, National Institutes of Health and Unilever R&D (latter provided unrestricted grant for distribution of trial margarines)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	On the computer by a random number generator before the start of the trial
Allocation concealment (selection bias)	Low risk	Author confirmed allocation was concealed from clinicians/ researchers
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The 4 types of margarine were "similar in taste, texture and colour". A trained test panel did not perceive a fishy taste or odour. Randomisation tables were stored safely under supervision.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Randomisation tables were stored safely under supervision. There was an independent statistician for data analysis. Quote: "Events were coded by three members of the end‐point adjudication committee who were unaware of the identity of the patient, the identity of the treating physician and the patients assigned study group".
Incomplete outcome data (attrition bias) All outcomes	Low risk	All patients were followed up for events computerised linkage with municipal registries. 2531 patients were only followed up for baseline anthropometric and medical measurements.
Selective reporting (reporting bias)	High risk	Sudden cardiac death endpoint omitted. Registered from August 2005, recruitment was from 2002 to 2006. Outcomes papers published in 2010
Attention	Low risk	All participants appear to have had similar frequency and quantity of attention and follow‐up
Compliance	Low risk	Unused margarine tubs were returned; daily intakes of margarine and n‐3 fatty acids were calculated on the basis of the amount unused. Adherence was measured by levels of fatty acids in plasma cholesteryl esters, margarine and questionnaires. 90.5% of patients adhered to the protocol and consumed 20.6 (SD 2.8) g of margarine/d
Other bias	Low risk	None noted