HARP 1995.
| Methods | Harvard Atherosclerosis Reversibility Project (HARP) RCT, (n‐3 EPA + DHA vs MUFA), 24 months Summary risk of bias: moderate or high |
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| Participants | Patients with coronary heart disease N: 41 intervention, 39 control (99.9% follow‐up at study end) Level of risk for CVD: high Men: 93.5% intervention, 92.9 % control Mean age in years (SD): 62 (7) intervention, 62 (7) years control Age range: 30‐75 Smokers: 0% (exclusion criteria) Hypertension: 48% intervention, 36% control Medications taken by at least 50% of those in the control group: beta blockers, antiplatelet agents Medications taken by 20%‐49% of those in the control group: calcium channel blockers, nitrates Medications taken by some, but less than 20% of the control group: ACE inhibitors, oral hypoglycaemic drugs Location: USA Ethnicity: not reported |
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| Interventions | Type: supplement (capsule) Comparison: LCn3 vs MUFA Intervention: 12 fish oil capsules/day (Promega, Parke‐Davis) in divided doses, preferably after meals. Each fish oil capsule contained 500 mg of n‐3 polyunsaturated fatty acids composed of EPA (240 mg), DHA (160 mg) and other (100 mg) (mainly DPA) providing total daily dose of 6 g of n‐3 fatty acids. Dose: 6 g/d LCn3 Control: olive oil capsules identical in appearance to the fish oil capsules. Compliance: capsule counts and serum level measurements. Adherence averaged 80% intervention, and 90% control with significant levels of adipose n‐3 fatty acids in the fish oil group. Duration of intervention: average 28 months |
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| Outcomes | Main study outcome: regression of coronary artery lesions Dropouts: 10 intervention, 11 control Available outcomes: all‐cause and CV deaths, fatal and non‐fatal MI, stroke, angioplasty or CABG, unstable angina, CHD, cancer diagnosis, combined CV events, side effects Response to contact: yes | |
| Notes | Study funding: National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland, Warner Lambert‐Parke Davis, East Hanover, New Jersey; and by an Established Investigator Award to Dr Sacks from the American Heart Association, Dallas, Texas | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "randomization" stratified by clinical management regime and total/HDL cholesterol ratio |
| Allocation concealment (selection bias) | Unclear risk | No further details |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Quote: "patients and personnel responsible for lab measurements, cardiac catheterization, and analysis of angiography films were blinded to the treatment assignment". Although capsules were identical in appearance, no information on their taste and smell |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "patients and personnel responsible for lab measurements, cardiac catheterization, and analysis of angiography films were blinded to the treatment assignment" |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Low attrition rate over 28 months and all reasons are well documented |
| Selective reporting (reporting bias) | High risk | Trial registered retrospectively after publication |
| Attention | Low risk | Nothing in description implies the arms were treated differently |
| Compliance | Low risk | Very clear (P < 0.001) differences between arms for the 3 main n‐3 components in the fish oil |
| Other bias | Low risk | None noted |