Trial assesses cardiovascular benefit in patients with diabetes.
There exists a fair body of evidence that suggests a correlation between regular ingestion / supplementation of omega 3 fatty acids and reduced cardiovascular risk. Consequently, the American Heart Association suggests use of omega 3 fatty acid supplements for prevention of secondary coronary heart disease. Likewise, several heart disease prevention guidelines include a recommendation to regularly consume fish as a means of primary prevention. However, the vast majority of supporting literature consists of observational studies. This correlation has, thus far, remained unsubstantiated by more robust randomized controlled trials. The randomized controlled trials that were conducted looked mostly at relatively healthy individuals with few comorbidities. Patients with diabetes are roughly 2 to 3 times as likely to develop cardiovascular disease as their counterparts without diabetes. With this in mind, even a slight cardiovascular benefit may have a relatively large impact in the population of patients who have diabetes (one that might not have been noticed in a population without diabetes). This trial aims to evaluate the utility of omega 3 fatty acid supplementation for the prevention of cardiovascular disease in patients with diabetes.
As this trial’s aim is to determine causality, a randomized controlled factorial trial was selected as the study design. The outcome of interest was the occurrence of the first major cardiovascular event. A composite outcome of a first occurrence of a cardiovascular event in addition to any arterial revascularization was assessed secondarily. Patients were considered for inclusion if they were at least 40 years of age with any form of diabetes and no prior history or evidence of cardiovascular disease. The principle exclusion criteria were any clear indication / contraindication for use of omega 3 fatty acids or aspirin. Once deemed eligible, patients were randomized into either the intervention group (receiving a 1-gram capsule containing 380 mg of docosahexanoic acid and 460 mg of eicosapentaenoic acid, to be taken once daily) or the control group (receiving a placebo in an identical dosage form, to be taken once daily). The same group of participants were then re-randomized to receive either 100 mg of aspirin or identical placebo, thus creating 2 subgroups for each of the intervention groups (omega 3 fatty acid ± aspirin and placebo ± aspirin). Patients were assessed via mailed questionnaires sent at 6-month intervals during the 7.5-year study. Statistical significance was determined via the log rank test.
A total of 121,254 individuals were assessed for eligibility. Of those, 105,774 were excluded due to ineligibility or refusal to participate. There were 15,480 participants who were ultimately deemed eligible and randomized into their respective groups, achieving a reported power of 90% for detecting a difference between intervention groups for the primary outcome.
Baseline characteristics between groups were equivalent. For the primary outcome, there were 689 major cardiovascular events in the fatty acid group (8.9%) compared to 712 in the placebo group (9.2%). When analyzed, there was found to be no statistically significant difference between groups (p=0.55). Likewise, no significant difference existed between groups for the secondary outcome (major cardiovascular event or arterial revascularization). Analysis of the study subgroups yielded similarly insignificant results.
The results of this study suggest that supplementation of omega 3 fatty acids does not significantly affect risk of major cardiovascular events in patients with diabetes. These results align with those of previous randomized controlled trials which focused on general populations rather than specifically on patients with diabetes. Consequently, omega 3 fatty acid supplementation should not be routinely recommended for the prevention of cardiovascular events and certainly should not be considered as an alternative for an agent with proven cardiovascular benefit.
- Evidence suggests that supplementation of omega 3 fatty acids does not significantly reduce the risk of a major cardiovascular event in patients with diabetes.
- Omega 3 fatty acid supplementation should not be routinely recommended for the prevention of cardiovascular events in patients with diabetes.
- Omega 3 fatty acid supplementation should not be considered an alternative to agents with proven cardiovascular benefit.
Bowman, Louise, et al., “Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus.” The New England Journal of Medicine, vol. 379, 2018, pp. 1540-1550, doi: 10.1056/NEJMoa1804989
Michael Zaccaro, Pharm. D. Candidate 2019, LECOM School of Pharmacy