GISSI‐P 1999.
| Methods | Gruppo Italiano per la Sperimentazione della Streptochinasi nell'Infarto Miocardico – Prevention (GISSI‐P) RCT, 2 × 2 (n‐3 EPA + DHA vs nil), 42 months Summary risk of bias: moderate or high |
|
| Participants | People with recent (≤ 3 months) MI N: 5666 intervention, 5658 control (99.9% follow‐up at trial end) Level of risk for CVD: high Men: 85.7% intervention, 84.9% control Mean age in years (SD): 59.3 (10.6) intervention, 59.5 (10.5) years control Age range: < 50 to > 80 Smokers: 42.6% intervention, 42.3% control Hypertension: 36.2% intervention, 34.9% control Medications taken by at least 50% of those in the control group: anti‐platelet Medications taken by 20%‐49% of those in the control group: ACE inhibitors, beta‐blockers Medications taken by some, but < 20% of the control group: lipid‐lowering Location: Italy Ethnicity: not reported |
|
| Interventions | Type: supplement (capsule) Comparison: EPA + DHA vs nil Intervention: gelatin capsules of omega‐3‐acid ethyl esters 90 (Omacor), 1/d (850‐882 mg/d EPA + DHA daily, ratio 1:2) Dose: ˜0.866 g/d EPA + DHA Control: nil (no placebo) Compliance: capsule counts, 11.6% had stopped taking Omacor by 12 months, 28.5% by the end of the trial Duration of intervention: median follow‐up 40 months |
|
| Outcomes | Main trial outcome: all‐cause mortality, CV mortality, stroke, MI Dropouts: unclear (however, all randomised were included in analyses) Available outcomes: total, sudden and CV deaths, MI, stroke, angioplasty or CABG, angina, CHD, cancer diagnosis, cancer death, combined CV events, side effects Response to contact: no |
|
| Notes | Numbers are slightly different in different publications (Lancet 1999 paper used as main source). Half of both groups were on vitamin E supplements (300 mg/d synthetic α‐tocopherol) as this was the other 2 × 2 intervention. Trial funding: Bristol Meyers Squibb, Pharmacia Upjohn, Societa Produtti Antibiotici, Pfizer |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Telephone/computer network, stratified by hospital, based on a biased coin algorithm |
| Allocation concealment (selection bias) | Low risk | Randomisation by telephone with the co‐ordinating centre |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | No placebo intervention (capsule vs nil) so participants not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | "validation of clinical events ... was assured by an ad‐hoc committee of expert cardiologists and neurologists blinded to patients treatment assignment" |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Clearly described, good follow‐up (< 28% dropped out over 3.5 years) |
| Selective reporting (reporting bias) | Unclear risk | No trial protocol or trials registry entry was found |
| Attention | Low risk | Slight as no placebo, otherwise similar |
| Compliance | Unclear risk | Capsule counts, 11.6% had stopped taking Omacor by 12 months, 28.5% by the end of the trial |
| Other bias | Low risk | No further bias noted |