Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione.
BACKGROUND
Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction.


RESULTS
In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths.


CONCLUSIONS
The early effect of low-dose (1 g/d) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies.
Marchioli
Roberto
R
Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy. marchioli@negrisud.it
Barzi
Federica
F
Bomba
Elena
E
Chieffo
Carmine
C
Di Gregorio
Domenico
D
Di Mascio
Rocco
R
Franzosi
Maria Grazia
MG
Geraci
Enrico
E
Levantesi
Giacomo
G
Maggioni
Aldo Pietro
AP
Mantini
Loredana
L
Marfisi
Rosa Maria
RM
Mastrogiuseppe
G
G
Mininni
Nicola
N
Nicolosi
Gian Luigi
GL
Santini
Massimo
M
Schweiger
Carlo
C
Tavazzi
Luigi
L
Tognoni
Gianni
G
Tucci
Corrado
C
Valagussa
Franco
F
D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016757:Death, Sudden, Cardiac / Q000517:prevention & control*; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000401:mortality
D000889:Anti-Arrhythmia Agents; D015525:Fatty Acids, Omega-3; D008055:Lipids