GISSI‐HF 2008

Methods	Gruppo Italiano per la Sperimentazione della Streptochinasi nell'Infarto Miocardico – Heart Failure (GISSI‐HF) RCT, parallel, 2 arms (n‐3 EPA + DHA vs MUFA), 3.9 years Summary risk of bias: moderate or high
Participants	Patients with chronic heart failure N: 3494 intervention, 3481 control Level of risk for CVD: high Men: 77.8% intervention, 78.8% control Mean age: 67 (11) intervention,67 (11) control Age range: 18+ years Smokers: 14.4% intervention, 13.9% control Hypertension: 54.0% intervention, 55.2% control Medications taken by at least 50% of those in the control group: ACE inhibitors, beta‐blockers, diuretics Medications taken by 20%‐49% of those in the control group: spironolactone, digitalis, oral anticoagulants, aspirin, nitrates, statin Medications taken by some, but less than 20% of the control group: ARBs, other antiplatelets, calcium channel blockers, amiodarone Location: Italy Ethnicity: unclear
Interventions	Type: supplement (capsule) Comparison: EPA + DHA vs MUFA Intervention:1 capsule per day of 1 g n‐3 mainly EPA and DHA as ethyl esters in the average ratio of 1:1.2. Dose: ˜0.866 g/d EPA + DHA Control: 1 g/d matching olive oil placebo capsule Compliance: unclear Length of intervention: median 3.9 years
Outcomes	Main study outcome: time to death or admission to hospital for cardiovascular reasons Dropouts: 34 intervention, 46 control (1004 intervention and 1029 control stopped study treatment) Available outcomes: mortality, CV mortality, MI, stroke, new heart failure, incident AF, resumed arrhythmia gatalitis Response to contact: yes (no data provided)
Notes	Study funding: funders included Pfizer, AstraZeneca and others
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomly assigned (with stratification by site) to treatment groups
Allocation concealment (selection bias)	Low risk	Randomly assigned (with stratification by site) to treatment groups by a concealed computerised telephone randomisation system
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double blinding stated, but taste not reported as masked and blinding of participants not checked
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All events "adjudicated blindly by an ad‐hoc committee on the basis of pre‐agreed definitions and procedures"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Reasons for attrition and exclusion were stated and addressed. Numbers in each intervention compared to numbers were similar.
Selective reporting (reporting bias)	Unclear risk	Published rationale and design (Tavazzi 2004) suggested primary outcomes were deaths and death or CV hospitalisation (published). Secondary outcomes not stated and no trials registry entry found
Attention	Low risk	Scheduled clinic visits at 1, 3, 6 months then 6 monthly until the end of the trial (for both arms)
Compliance	Unclear risk	No details
Other bias	Low risk	No further bias noted