n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia.
BACKGROUND
The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown.


METHODS
In this double-blind study with a 2-by-2 factorial design, we randomly assigned 12,536 patients who were at high risk for cardiovascular events and had impaired fasting glucose, impaired glucose tolerance, or diabetes to receive a 1-g capsule containing at least 900 mg (90% or more) of ethyl esters of n-3 fatty acids or placebo daily and to receive either insulin glargine or standard care. The primary outcome was death from cardiovascular causes. The results of the comparison between n-3 fatty acids and placebo are reported here.


RESULTS
During a median follow up of 6.2 years, the incidence of the primary outcome was not significantly decreased among patients receiving n-3 fatty acids, as compared with those receiving placebo (574 patients [9.1%] vs. 581 patients [9.3%]; hazard ratio, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72). The use of n-3 fatty acids also had no significant effect on the rates of major vascular events (1034 patients [16.5%] vs. 1017 patients [16.3%]; hazard ratio, 1.01; 95% CI, 0.93 to 1.10; P=0.81), death from any cause (951 [15.1%] vs. 964 [15.4%]; hazard ratio, 0.98; 95% CI, 0.89 to 1.07; P=0.63), or death from arrhythmia (288 [4.6%] vs. 259 [4.1%]; hazard ratio, 1.10; 95% CI, 0.93 to 1.30; P=0.26). Triglyceride levels were reduced by 14.5 mg per deciliter (0.16 mmol per liter) more among patients receiving n-3 fatty acids than among those receiving placebo (P<0.001), without a significant effect on other lipids. Adverse effects were similar in the two groups.


CONCLUSIONS
Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).
Jackie
J
Bosch
Hertzel C
HC
Gerstein
Gilles R
GR
Dagenais
Rafael
R
Díaz
Leanne
L
Dyal
Hyejung
H
Jung
Aldo P
AP
Maggiono
Jeffrey
J
Probstfield
Ambady
A
Ramachandran
Matthew C
MC
Riddle
Lars E
LE
Rydén
Salim
S
Yusuf
D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D017211:Treatment Failure; D014280:Triglycerides / Q000097:blood
D015525:Fatty Acids, Omega-3; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D014280:Triglycerides; D000069036:Insulin Glargine; D002784:Cholesterol