Uses and benefits of omega-3 ethyl esters in patients with cardiovascular disease

Figures & data

Figure 1 Randomized controlled trials reporting the effect of n-3 PUFA on cardiac death.

Abbreviations: CI, confidence interval; PUFA, polyunsaturated fatty acids.

Table 1 GISSI-Prevenzione. Overall efficacy profile of n-3 PUFA, vitamin E, and n-3 PUFA + vitamin E treatment

	Rate of events				Four-way analysis			Two-way analysis with interaction term	Two-way analysis without interaction term
	Omega-3 EE (n = 2835)	Vitamin E (n = 2830)	Omega-3 EE + vitamin E (n = 2830)	Control (n = 2828)	Omega-3 EE relative risk (95% CI)	Vitamin E relative risk (95% CI)	Omega-3 EE + vitamin E relative risk (95% CI)	Omega-3 EE relative risk (95% Cl)	Omega-3 EE relative risk (95% Cl)
Main endpoints
Death, nonfatal MI and nonfatal stroke	358 (12.6%)	376 (13.3%)	360 (12.7%)	419 (14.8%)	0.84 (0.73–0.97)	0.89 (0.78–1.03)	0.85 (0.74–0.98)	0.84 (0.73–0.97)	0.90 (0.81–0.99)
CVD death, nonfatal MI and nonfatal stroke	266 (9.4%)	291 (10.3%)	290 (10.3%)	330 (11.7%)	0.80 (0.68–0.94)	0.88 (0.75–1.03)	0.87 (0.74–1.02)	0.80 (0.68–0.94)*	0.89 (0.79–0.99)
Secondary analyses
All fatal events	239 (8.4%)	255 (9.0%)	238 (8.4%)	299 (10.6%)	0.80 (0.67–0.94)	0.85 (0.72–1.00)	0.79 (0.67–0.94)	0.79 (0.67–0.94)	0.85 (0.76–0.97)
CVD death	144 (5.1%)	166 (5.9%)	166 (5.9%)	204 (7.2%)	0.70 (0.56–0.86)	0.81 (0.66–0.99)	0.81 (0.66–0.99)	0.70 (0.56–0.86)**	0.83 (0.72–0.97)
Cardiac death	113 (4.0%)	134 (4.7%)	134 (4.7%)	172 (6.1%)	0.65 (0.51–0.82)	0.78 (0.62–0.97)	0.77 (0.62–0.97)	0.65 (0.51–0.82)**	0.80 (0.68–0.95)
Coronary death	101 (3.6%)	112 (4.0%)	108 (3.8%)	146 (5.2%)	0.68 (0.53–0.88)	0.76 (0.60–0.98)	0.73 (0.57–0.94)	0.68 (0.53–0.88)*	0.80 (0.67–0.97)
Sudden death	52 (1.8%)	62 (2.2%)	59 (2.1%)	92 (3.3%)	0.56 (0.40–0.79)	0.67 (0.49–0.93)	0.64 (0.46–0.88)	0.56 (0.40–0.79)**	0.72 (0.56–0.91)
Other death	95 (3.3%)	89 (3.1%)	72 (2.5%)	95 (3.4%)	0.99 (0.74–1.31)	0.93 (0.70–1.24)	0.75 (0.55–1.02)	0.99 (0.74–1.31)	0.90 (0.73–1.11)
Unknown cause	35 (1.2%)	34 (1.2%)	24 (0.9%)	51 (1.8%)	0.68 (0.44–1.04)	0.66 (0.43–1.02)	0.47 (0.29–0.76)	0.68 (0.44–1.04)	0.69 (0.49–0.96)
Non-CVD death	60 (2.1%)	55 (1.9%)	48 (1.7%)	44 (1.6%)	1.35 (0.91–1.98)	1.24 (0.84–1.85)	1.08 (0.72–1.63)	1.35 (0.91–1.98)	1.08 (0.82–1.42)
Nonfatal CVD events	138 (4.9%)	144 (5.1%)	141 (5.0%)	139 (4.9%)	0.98 (0.78–1.24)	1.03 (0.82–1.30)	1.01 (0.80–1.27)	0.98 (0.78–1.24)	0.98 (0.83–1.15)
Nonfatal MI	104 (3.7%)	120 (4.2%)	119 (4.2%)	113 (4.0%)	0.91 (0.70–1.18)	1.06 (0.82–1.37)	1.05 (0.81–1.35)	0.91 (0.70–1.18)	0.95 (0.79–1.14)
Nonfatal stroke	37 (1.3%)	27 (1.0%)	25 (0.9%)	30 (1.1%)	1.22 (0.75–1.98)	0.90 (0.53–1.51)	0.83 (0.49–1.40)	1.22 (0.75–1.98)	1.08 (0.75–1.55)
Subsidiary analyses
CHD death and nonfatal MI	198 (7.0%)	224 (7.9%)	220 (7.8%)	251 (8.9%)	0.78 (0.65–0.94)	0.89 (0.74–1.06)	0.87 (0.73–1.04)	0.78 (0.65–0.94)*	0.87 (0.77–0.99)
Fatal and nonfatal stroke	50 (1.8%)	37 (1.3%)	42 (1.5%)	40 (1.4%)	1.24 (0.82–1.87)	0.92 (0.59–1.44)	1.04 (0.67–1.60)	1.24 (0.82–1.87)	1.19 (0.88–1.60)
PTCA or CABG	588 (20.7%)	538 (19.0%)	584 (20.6%)	575 (20.3%)	1.01 (0.90–1.14)	0.93 (0.82–1.04)	1.02 (0.90–1.14)	1.01 (0.90–1.14)	1.05 (0.97–1.14)

Patients with two or more events of different types appear more than once in columns but only once in rows. P value for interaction.

* <0.10;

** <0.05. Relative risk, calculated by Cox regression analysis.

Abbreviations: CVD, cardiovascular disease; MI, myocardial infarction; CHD, coronary heart disease; PTCA, coronary angioplasty; CABG, coronary artery bypass grafting.

Table 2 GISSI-HF primary outcomes, secondary outcomes, and causes of death

	n-3 PUFA (n = 3494)	Placebo (n = 3481)	Adjusted HR (95% CI)*	Pvalue
Primary outcomes
Deaths from any cause	955 (27.3%)	1014 (29.1%)	0.91 (0.833–0.998)	0.041
Deaths from any cause or admitted in hospital for CV reasons	1981 (56.7%)	2053 (58.9%)	0.92 (0.849–0.999)	0.009
Secondary outcomes
Deaths from a CV cause	712 (20.4%)	765 (22.0%)	0.90 (0.81–0.99)	0.045
Patients who had a SCD	307 (8.8%)	325 (9.3%)	0.93 (0.79–1.08)	0.333
Patient admissions:	1986 (56.8%)	2028 (58.3%)	0.94 (0.88–1.00)	0.049
For a CV reason	1635 (46.8%)	1687 (48.5%)	0.93 (0.87–0.99)	0.026
For HF	978 (28.0%)	995 (28.6%)	0.94 (0.86–1.02)	0.147
Deaths from a CV cause or admitted for any reason	2157 (61.7%)	2202 (63.3%)	0.94 (0.89–0.99)	0.043
Patients with fatal and nonfatal MI	107 (3.1%)	129 (3.7%)	0.82 (0.63–1.06)	0.121
Patients with fatal and nonfatal stroke	122 (3.5%)	103 (3.0%)	1.16 (0.89–1.51)	0.271
Causes of death
Acute MI	20 (0.6%)	25 (0.7%)	0.77 (0.43–1.39)	0.382
Worsening HF	319 (9.1%)	332 (9.5%)	0.92 (0.79–1.07)	0.275
Presumed arrhythmic	274 (7.8%)	304 (8.7%)	0.88 (0.75–1.04)	0.141

Notes:

* 95% CI was calculated with a Cox proportional hazards model with adjustment for admission to hospital for heart failure in the preceding year, previous pacemaker, and aortic stenosis. Data are number (%) unless otherwise stated.

Abbreviations: CI, confidence interval; CV, cardiovascular; HF, heart failure; HR, hazards ratio; MI, myocardial infarction; PUFA, polyunsaturated fatty acids; SCD, sudden cardiac death.

Figure 2 GISSI-Prevenzione study: Number of lives saved in every 1000 post-MI patients treated with omega-3 EE 1000 mg/day for one year.

Abbreviations: CV, cardiovascular; EE, ethyl esters; MI, myocardial infarction.

Figure 3 GISSI-HF study: Number of events avoided every 1000 HF patients treated with omega-3 EE 1000 mg/day for one year.

Abbreviations: CV, cardiovascular; EE, ethyl esters; MI, myocardial infarction.