Table 2: (a) Major clinical trial data for primary and secondary prevention of cardiovascular disease. (b) Major clinical trial data on antiarrhythmic end points.
(a)

StudyDose of FAsControl FollowupPrior MI/CADMortality Nonfatal MIAll CVDeventsStroke
All-causeCardiacSCD

RCTs, blinded

Omega [54]1 g/d n-3 FAs1 g Olive oil 3851 1 Year 100%1.25
(0.90–1.72)
0.95
(0.56–1.60)
1.21
(0.96–1.52)
Alpha Omega
Trial [55]
226 mg EPA +
150 mg DHA
1.9 g ALA or placebo 4837 40 Months 100%1.01
(0.82–1.24)
0.95
(0.68–1.32)
1.1
(0.87–1.17)
GISSI-HF [56]1 g/d n-3 FAs Placebo 6975 3.9 Years 41.8%0.91
(0.83–0.99)
0.93
(0.79–1.08)
ORIGIN [64]1 g n-3 FAs1 g Olive oil12536 6 Years 59%0.98
(0.89–1.07)
1.10
(0.93–1.30)
1.01
(0.93–1.10)
0.92
(0.79–1.08)
OFAMI [74]4 g n-3 FAs4 g Corn oil 300 18 Months 100%1.0
(0.45–2.2)
1.0
(0.39–2.6)
1.4
(0.7–2.6)
1.1
(0.84–1.3)
IEIS-4 [67]1.08 g EPA2.9 ALA or placebo 360 1 Year 100%0.52
(0.29–0.95)
0.24
(0.05–1.1)
0.52
(0.3–0.9)
0.71
(0.48–1.1)

RCTs, unblended

DART [52]Fish 200–400 g/weekFruits and vegetables 2033
male
2 Years 100%0.71
(0.54–0.93)
0.84
(0.66–1.07)
GISSI [53]1 g/d n-3 FAsVitamin E or placebo11324 3.5 Years 100%0.79
(0.66–0.93)
0.65
(0.51–0.82)
0.55
(0.51–0.82)
0.91 (0.68–0.94) 0.80
(0.68–0.94)
1.2
(0.81–1.9)
JELIS [61]1800 mg EPA Statin18645 4.6 Years 20%1.09
(0.92–1.28)
0.94
(0.57–1.56)
1.06
(0.55–2.07)
0.75 (0.54–1.04)0.81
(0.69–0.95)
1.02
(0.91–1.13)
DART 2 [75]2 meals of fish/week or 3 g
n-3 FA suppl.
Intake of fruits, vegetables, and oats 3114 3–9 Years 100%1.15
(0.96–1.36)
1.26
(1.0–1.56)
1.54
(1.06–2.23)

Observational

Nurses’ Health
Study [66]
Intake of fish
(meals/week)
84688 16 Years 0% 0.55
(0.33–0.90)
0.73
(0.51–1.04)
0.66
(0.50–0.89)
The Physicians’ health study [71]Intake of fish
(meals/week)
21185 4 Years1.2
(0.6–2.2)
The Zutphen study [70]Intake of fish
(meals/week) or estimated EPA + DHA/d
1373 40 Years 0%0.73
(0.47–1.13)
0.89
(0.34–2.30)
JPHC study [60]Quintiles of fish intake41578 10 Years 0%1.08
(0.42–2.76)
1.14
(0.36–3.63)
0.43
(0.23–0.81)
WENBIT [63]Quartiles of
n-3 FA intake
2412 57 Months 90%1.11 (0.73–1.67)1.35
(0.75–2.42)

(b)

StudyInclusion criteriaPrior MI/CADDose of FAsControl FollowupEndpointEvent rate (%)

RCTs, blinded

Leaf et al. [47]ICD due to SCA, spontaneous or inducible sustained VT. 78%4 g/day
n-3 FAs
4 g corn oil 402 12 monthsTime to first ICD-event for VT/VFRate of ICD-event:
28% (n-3 FAs) versus 39%, RR 0.67 (0.47–0.95)
Brouwer et al. [78]
(SOFA)
One episode of spontaneous VT or VF in the preceding year, ICD implanted 70%0.9 g/day
n-3 FAs
2 g high-oleic acid sun-lower oil 546 12 monthsAppropriate ICD intervention for VT or VF, or all-cause death30% versus 33% with sustained ICD intervention or death
HR 0.86 (0.64–1.16)
Finzi et al. [79]
(GISSI-HF)
ICD due to SCA, sustained VT or for primary prevention of syncope. 41.7%1 g/day
n-3 FAs
Placebo 566 928 daysIncidence of ICD-interventionsICD events 27.3% versus 34.0%, HR 0.80 (0.59–1.09). Mortality 26.6% versus 24.3%, HR 1.25 (0.89–1.75)
Raitt et al. [80]ICD and a recurrent episode of VT or VF. 73%1.8 g/day
n-3 FAs
(1.3 g EPA/
DHA)
Olive oil
(73% oleic acid)
200 2 yearsTime to first ICD-event for VT/VF and frequency of recurrent VT/VF events65% versus 59% with ICD therapy. Recurrent VT/VF more common in n-3 FA group ( )

RCTs, non-blinded

Madsen et al. [81]Inducible sustained monomorphic VT 83%3.9 g
n-3 FAs
0.9% saline 6Level of stimulation required to induce monomorphic VT2 of 6 noninducible
2 of 6 increased stimulation required

Intervention studies, non-randomized

Schrepf et al. [45]Repeated episodes of sustained VT 90%3.8 g
n-3 FAs as IV infusion
10Inducibilty of sustained VT in patients with a positive test at baseline2 of 7 patients (29%)
Metcalf et al. [44]ICD and inducible sustained monomorphic VT 100%3 g/day
n-3 FAs
No dietary manipulation 26 6 weeksLevel of stimulation required to induce monomorphic VT42% versus 7% without inducible VT.

Observational

Aarsetoey et al. [82]SCA with documented VF during the ischemic phase of an MI 100%Blood omega-3 indexOmega-3 index in MI patients without SCA 195The omega-3 index in SCA patients versus MI patients free of SCA1% increase of the omega-3 index associated with 48% reduction in risk of VF

RCT: randomized controlled trial, EPA: eicosapentaenoic acid, DHA: docosahexaenoic acid, ALA: alpha-linolenic acid, VT: ventricular tachycardia, VF: ventricular fibrillation, and SCA: sudden cardiac arrest.