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ORIGIN n-3 Fatty Acids

"N-3 Fatty Acids in High-Risk Patients with Dysglycemia". The New England Journal of Medicine. 2012. 367(4):309-318. PubMed • Full text • PDF

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

In high-risk patients with dysglycemia, does daily supplementation with n-3 fatty acids reduce the rate of cardiovascular events?

Bottom Line

Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in high-risk patients with dysglycemia.

Major Points

Patients with type 2 diabetes or at high risk for diabetes are at an increased risk of cardiovascular events. Previous studies have suggested that n-3 fatty acids may have cardiovascular benefits, but evidence in patients with dysglycemia has been limited.

Guidelines

At the time of the study publication, the usage of n-3 fatty acids for the reduction of cardiovascular events in high-risk patients with dysglycemia was not established in guidelines.

Design

- Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial
- N=12,536
- Interventions: 1 g capsule of at least 900 mg (90% or more) ethyl esters of n-3 fatty acids (n=6,281) or placebo (n=6,255)
- Median follow-up: 6.2 years

Population

- Inclusion Criteria: Patients ≥50 years old with impaired fasting glucose, impaired glucose tolerance, or diabetes at high risk for cardiovascular events
- Exclusion Criteria: Unwillingness to discontinue non-study n-3 supplements, HbA1c ≥9%, recent CABG without subsequent cardiovascular event, severe heart failure, active cancer affecting survival
- Baseline Characteristics: Mean age 64 years, 65% men, 59% had previous myocardial infarction, stroke, or revascularization

Interventions

- 1 g capsule of n-3 fatty acids daily containing 465 mg of EPA and 375 mg of DHA
- Placebo capsule containing approximately 1 g of olive oil

Outcomes

Primary Outcome
- Death from cardiovascular causes: 9.1% in n-3 fatty acids group vs. 9.3% in placebo group (HR 0.98; 95% CI, 0.87 to 1.10; P=0.72)

Secondary Outcomes
- Major vascular events: 16.5% vs. 16.3% (HR 1.01; 95% CI, 0.93 to 1.10; P=0.81)
- Death from any cause: 15.1% vs. 15.4% (HR 0.98; 95% CI, 0.89 to 1.07; P=0.63)
- Death from arrhythmia: 4.6% vs. 4.1% (HR 1.10; 95% CI, 0.93 to 1.30; P=0.26)
- Triglyceride levels reduced by 14.5 mg per deciliter more in n-3 fatty acids group (P<0.001)

Criticisms

- The daily dose of n-3 fatty acids may have been too low to demonstrate a benefit.
- Assessment of the effect of n–3 fatty acids based on dietary intake was conducted through a questionnaire rather than serum level measurement.

Funding

- Funded by Sanofi, with study drugs provided by Pronova BioPharma Norge.