Prevention of sudden cardiac death with omega-3 fatty acids in patients with coronary heart disease: A meta-analysis of randomized controlled trials

Figures & data

Table

SCD	sudden cardiac death
CHD	coronary heart disease
MI	myocardial infarction
RCT	randomized controlled trials
PTCA	percutaneous transluminal coronary angioplasty
EPA	eicosapentaenoic acid
DHA	docosahexaenoic acid
CART	the Coronary Angioplasty Restenosis Trial
JELIS	Japan eicosapentaenoic acid lipid intervention study
GISSI-P	the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico
CI	confidence interval
RR	relative risk
ATPase	adenosine triphosphatase
CAST	Cardiac Arrhythmia Suppression Trial

Figure 1.  The selection process for RCTs of omega-3 fatty acids. The Quality of Reporting of Meta-analyses (QUOROM) flow diagram describes the screening process and exclusion criteria for RCTs of omega-3 fatty acids. Eight trials met the inclusion criteria. (RCT = randomized controlled trial.)

Table I.  Characteristics of randomized controlled trials of omega-3 fatty acid in the meta-analysis.

Study	Inclusion criteria	Regimen	History of MI (%)	Regimen	Age (years)	Men (%)	Mean follow-up (month)	Statin (%)	Beta-blocker (%)	Jadad ^a
de Lorgeril 1994	Post MI	Intervention	100	Alpha-linolenic acid, ∼2 g/d	53.5	89.4	46	-	60.2	3
		Control	100	Dietary advice	53.5	92.1		-	63.4
Leaf A 1994	CHD with PTCA	Intervention	33	4.1 g/d EPA; 2.8 g/d DHA	63	77	6	-	-	3
		Control	33	Corn oil	58	81		-	-
Singh RB 1997	Suspected AMI	Intervention	90.1	1.08 g/d EPA; 0.72 g/d DHA	48.5	91.8	12	-	29.4	5
		Control	84.6	Al(OH)3, 0.1 g/d	49.2	93.3		-	24.9
CART 1999	CHD with PTCA	Intervention	51	Omega-3 fatty acid 5.1 g/d	60	74.5	6	9.2	76.5	5
		Control	50	Corn oil	59	80.7		16.7	72.9
GISSI-P 2002	Post MI	Intervention	100	EPA, 0.3 g/d; DHA 0.6 g/d	59.2	85.7	42	4.6	43.9	2
		Control	100	No intervention	59.4	84.9		4.9	44.2
Singh RB 2002	High risk CHD	Intervention	83	Rich in linolenic acid (3.487–4.963 g/d) ^b	49	91	24	7	-	3
		Control	83	Diet	48	88		6	-
Burr 2003	Stable angina	Intervention	0	Oily fish 2 portions/week or fish oil (Maxepa) 3 g/day (0.54 g/d EPA; 0.36 g/d DHA) ^c	61	100	108	-	42.4	2
		Control	0	Fruit vegetables and oats	61	100		-	40.6
JELIS 2007	CHD	Intervention	30.0	EPA, 1.8 g/d with statin	61	32	55	97	9	3
		Control	27.2	Statin alone	61	31		98	8

^aUsed to assess the quality of randomized controlled trials (range 1–5).

^bThe food composition was available in the web site: http://www.nal.usda.gov/fnic/foodcomp/search/ and http://www.nutritiondata.com/facts/fats-and-oils/507/2.

^cThe Maxepa composition was available in the web site: http://www.epgonline.org/viewdrug.cfm/letter/M/language/LG0001/drugId/DR001189/drugName/MAXEPA

AMI = acute myocardial infarction; CART = the Coronary Angioplasty Restenosis Trial; CHD = coronary heart disease; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; GISSI-P = the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico; JELIS = Japan eicosapentaenoic acid lipid intervention study. MI = myocardial infarction; PTCA = percutaneous transluminal coronary angioplasty;-= not available.

Table II.  Data on cardiac death and SCD in randomized controlled trials of omega-3 fatty acid.

Study	Regimen	No. of patients	SCD	Cardiac death	All-cause mortality
de Lorgeril 1994	Intervention	302	0	3	8
	Control	303	8	16	20
Leaf A 1994	Intervention	275	0	0	0
	Control	276	1	2	2
Singh RB 1997	Intervention	122	2	14	14
	Control	118	8	26	26
CART 1999	Intervention	250	1	1	1
	Control	250	1	3	3
GISSI-P 2002	Intervention	5665	111	247	477
	Control	5658	154	306	554
Singh RB 2002	Intervention	499	6	18	24
	Control	501	16	33	38
Burr 2003	Intervention	1571	73	180	283
	Control	1543	47	139	242
JELIS 2007	Intervention	1823	13	18	-
	Control	1841	13	21	-

CART = the Coronary Angioplasty Restenosis Trial; GISSI-P = the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico; JELIS = Japan eicosapentaenoic acid lipid intervention study; SCD = sudden cardiac death;- = not available.

Figure 2.  Prevention of sudden cardiac death with omega-3 fatty acids. Analysis of the randomized controlled trial (RCT) subgroup with a low proportion of myocardial infarction patients revealed a statistically non-significant trend of reduced sudden cardiac death. However, the subgroup with high proportion of myocardial infarction patients demonstrated a significant reduction in sudden cardiac death (SCD). Individual and pooled analysis demonstrated a non-significant 29% relative risk reduction (relative risk reduction = 1–relative risk, so one minus the relative risk of SCD (0.71) = 0.29) in sudden cardiac death.

Figure 3.  Prevention of cardiac death with omega-3 fatty acids. The high-incidence myocardial infarction subgroup showed a significant reduction in cardiac death. Individual and pooled analysis demonstrated a non-significant 29% relative risk reduction (relative risk reduction = 1–relative risk, so one minus the relative risk of sudden cardiac death (SCD) (0.71) = 0.29) in cardiac death.

Figure 4.  Effect of omega-3 fatty acids on all-cause mortality. The high-incidence myocardial infarction subgroup experienced a significant reduction in all-cause mortality. Individual and pooled analysis demonstrated a non-significant 23% relative risk reduction (relative risk reduction = 1–relative risk, so one minus the relative risk of sudden cardiac death (SCD) (0.77) = 0.23) in all-cause mortality.

Figure 5.  Effect of dietary or supplement sources of omega-3 fatty acids on sudden cardiac death. Sudden cardiac death was reduced in the randomized controlled trials (RCTs) in which omega-3 fatty acids were administered as a supplement (RR = 0.72; 95% CI: 0.58–0.91), but not in RCTs with diet or dietary advice (RR = 0.52; 95% CI: 0.12 to 2.22).