A randomized trial in patients with diabetes without evidence of cardiovascular disease has shown there to be no significant difference in the risk of serious cardiovascular events in those administered omega−3 fatty acids as compared to placebo.
In a population of patients with diabetes who are at a high risk of cardiovascular disease, the investigators aimed to determine if there were any options for supplements such as omega-3 fatty acids to have added effects on cardiovascular risk. The interest in omega-3 fatty acids stemmed from observational data, dating back several decades where there had been consistent observations that an increased dietary intake of fish was associated with a lower risk of cardiovascular disease. When the recruitment for the ASCEND trial began in 2005, the results from a trial conducted in Italy had shown promise. It was a trial of 11,000 heart attack survivors where the use of omega-3 fatty acids supplements in the same dose had indeed shown some benefits in terms of protection of cardiovascular events. Therefore, it was hypothesized that taking supplements including fatty acids might reduce cardiovascular risk in diabetics.
The ASCEND study collaborative group conducted a 2X2 factorial design trial, where patients were randomized to Aspirin or placebo. There was a second randomization where a total of 15, 480 patients were randomly assigned to receive 1-g capsules containing either omega−3 fatty acids or placebo (olive oil) daily, with a mean follow up duration of 7.4 years. The primary outcome was a serious vascular event which was a composite of nonfatal myocardial infarction or stroke, transient ischemic attack, or vascular death, excluding any hemorrhagic stroke. The secondary outcome comprised of a first serious vascular event or any arterial revascularization. The rate of adherence to the assigned treatment was 76%.
“Our study population was extremely well treated in terms of cardiovascular risk factors. About three-fourths of patients were on a statin, the majority of them were on antihypertensives, and diabetes was well controlled. In the context of all of those cardiovascular protective agents, the added benefit of other items such as omega- 3 fatty acids may as well be limited.”- Dr. Louise Bowman, M.D.
The results of the study were discouraging. A serious vascular event occurred in 8.9% of patients in the fatty acid group vs 9.2% in the placebo group (rate ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.55). There was no significant change in the composite outcome of a serious vascular event or revascularization, which occurred in 11.4% and 11.5% of patients of the fatty acid and placebo groups, respectively (rate ratio, 1.00; 95% CI, 0.91 to 1.09). Even death from any cause showed no difference with rates of 9.7% in the fatty acid group and 10.2% of the placebo group (rate ratio, 0.95; 95% CI, 0.86 to 1.05). Moreover, no significant between-group differences were reported in the rates of nonfatal serious adverse events.
Although disappointed by the findings, Dr. Louise Bowman, MD, of the University of Oxford in England stressed on the importance of the study saying, “Our study population was extremely well treated in terms of cardiovascular risk factors. About three-fourths of patients were on a statin, the majority of them were on antihypertensives, and diabetes was well controlled. In the context of all of those cardiovascular protective agents, the added benefit of other items such as omega- 3 fatty acids may as well be limited. Times have moved in terms of clinical practice. It’s great that we are doing a good job in treating these patients with diabetes and indeed cardiovascular risk was lower than expected when we first set out on the trial.”
In a contemporary diabetes population, well managed with cardioprotective agents, the evidence is increasingly consistent that there are no overall benefits that would justify the use of this 1g dose in a widespread fashion. However, Bowman acknowledged that there is interest in high dose (2-4g range of omega 3 fatty acid supplements), where an effect on triglyceride levels begins to be seen. Whether this mechanism translates into cardiovascular benefit remains unanswered. To throw further light on this, results from two ongoing trials (REDUCE-IT and STRENGTH trials), using a full therapeutic dose of 4g are eagerly awaited.