Table 4.

Clinical studies investigating the effect of n-3 poly-unsaturated fatty acids on secondary prevention for atrial fibrillation

Study design	Population	PUFA administration	PUFA quantification	AF diagnosis	Results
Double blind-RCT[30]	109 pts, age: 70 yr; Italy; heart structural abnormality: 90%; Amiodarone + ACE-i/ARBs: 100%	N-3 PUFA (EPA/DHA 1.2:1) 2 g/d, 1 mo before and 12 after ECV vs olive oil	No PUFA dosage	Weekly ECG for the first 3 wk after ECV and ECG + Holter ECG after 1, 3, 6, 12 mo and at symptoms occurrence	Less AF relapses with PUFA
Open-label randomized[31]	178 pts, Australia. Concomitant amiodarone, sotalol, ACE-i/ARBs	N-3 PUFA (EPA/DHA 1.3:1) 1.8 g/d for approximately 56 d before ECV and 1 year thereafter vs not	Serum dosage of EPA, DHA basally, before ECV	ECG at week 2 and 6 and every 3 mo. AF: ≥ 1 wk	Less AF relapses at 90 d and 1 yr with PUFA, P < 0.001; higher serum EPA, DHA
Double blind-RCT[33]	663 pts; paroxysmal AF: 18%; age: 60.5 yr; United States. No heart abnormality. Amiodarone: 0%, antiarrhythmic drugs: 13%; ACE-i/ARBs: 39%	N-3 PUFA (EPA/DHA 4.6:3.7; load: 8 g/d for 1 wk) 4 g/d for 24 wk vs oil	Serum DHA, EPA dosage basally, after 4 and 24 wk	Biweekly transtelephonic monitoring	No lower symptomatic AF recurrence in the paroxysmal and persistent
Prospective[35]	50 pts; ≥ 2 previous AF episodes; age: 54 yr, Japan. IC antiarrhythmic drugs: 100%	Observational period: no PUFA for 6 mo. Interventional period: EPA 1.8 g/d for 6 mo	Serum EPA, DHA dosage basally and at study end	Daily ECG monitoring and at symptoms occurrence	No lower AF burden and time to first relapse
Double blind-RCT[32]	204 pts, age: 69.3 yr; Italy. LAs 45 mm. First ECV: 59%; IC antiarrhythmic drugs: 29.5%, sotalol: 12.6%, amiodarone: 27.4%	N-3 PUFA (EPA/DHA 1.2:1) 3 g/d ≥ 1 wk before and 2 g/d after ECV for 6 mo vs olive oil	N-3 PUFA serum dosage basally, 6 mo after ECV	Transtelephonic monitoring: 2/first week after ECV and 3/wk for 3 mo + clinical visits after 7 d, 1, 3, 6 mo	No difference in ECV success, AF incidence, time to first relapse. Increase of EPA and DHA
Double blind RCT[36]	337 pts; symptomatic paroxysmal or persistent AF within 6 mo of enrollment	Fish oil (4 g/d) or placebo	Followed, on average, for 271 ± 129 d	Trans-telephonic event recorder, 12-lead ECG or Holter	No lower AF with PUFA
Double blind-RCT[37]	190 pts with paroxysmal or persistent AF	N-3 PUFAs (4 g/d; n = 126) or placebo (n = 64) in a 2:1 ratio	No PUFA dosage	Not specified	No reduction of AF recurrence and inflammation markers
Double blind-RCT[34]	586 pts with symptomatic paroxysmal AF requiring ECV (n = 428), at least 2 episodes of AF in the 6 mo before (n = 55), or both (103)	N-3 PUFA (1 g/d) or placebo for 12 mo	No PUFA dosage	Not specified	No lower AF with PUFA

RCTs: Randomized controller trials; pts: Patients; PO: Post-operative; AF: Atrial fibrillation; PUFA: Poly-unsaturated fatty acids; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; ACE-I: Angiotensin converting enzyme inhibitor; ARB: Angiotensin receptor blockers.