Prescription fish oil on front burner after huge win in REDUCE-IT
In what many clinicians believed was a rare breakthrough, the prescription fish oil icosapent ethyl cut the risk of ischaemic events among statin-treated patients with high triglyceride levels and either cardiovascular disease (CVD) or diabetes in the REDUCE-IT* trial, putting fish oil on the front burner.
While the trial demonstrated positive results for prescription fish oil, not all n-3 fatty acid preparations are equal, said lead investigator Dr Deepak Bhatt of Brigham and Women’s Hospital in Boston, Massachusetts, US who presented the findings at AHA 2018. “The result should not be generalized to other n-3 fatty acid preparations, in particular dietary-supplement preparations of n-3 fatty acid mixtures, which are variable and unregulated and have not been shown to have clinical benefits.”
Icosapent ethyl significantly reduced the primary endpoint of a composite of CV death, nonfatal MI, nonfatal stroke, coronary revascularization, and unstable angina over a median of 4.9 years (17.2 percent vs 22 percent with placebo, hazard ratio [HR], 0.75; p<0.001). [N Engl J Med 2018;doi:10.1056/NEJMoa1812792]
The key secondary endpoint of combined CV death, non-fatal MI, and non-fatal stroke also favoured icosapent ethyl (11.2 percent vs 14.8 percent, HR 0.74; p<0.001). Of note, CV death alone was reduced by 20 percent (4.3 percent vs 5.2 for placebo, HR 0.80), said Bhatt. REDUCE-IT stood out from previous trials of n-3 fatty acids and researchers theorized that it may be due to the low dose or low ratio of pure eicosapentaenoic acid (EPA) to docosahexaenoic acid used in the trial. Both the formulation (a highly purified and stable EPA ethyl ester) and dose (total daily dose, 4 g) used in REDUCE-IT were different from those in previous outcome trials of n-3 fatty acids.
Winner of fish oil battle?
There was no separation in the curves until 1 year, but the longer duration of the REDUCE-IT study could have been one of the reasons why the trial yielded positive results compared with previous studies of fish oil. To add to that, the fish oil used in REDUCE-IT is a highly purified EPA – it does not increase LDL and hence, may be superior to other fish oil supplements in the market, said the investigators.
Of importance is that the CV benefits held strong regardless of the patients’ triglyceride level at baseline and the levels achieved at 1 year, suggesting that some of the beneficial effects of icosapent ethyl (ie, lower ischaemic events risk) may be explained by metabolic effects.
The study included over 8,000 patients (median age 64 years, 28.8 percent were women) with established CVD or diabetes and other risk factors and who had elevated triglyceride levels despite being on a statin for at least 4 weeks. Seventy percent of patients were receiving treatment for secondary prevention of CV events, the rest for primary prevention. Patients received icosapent ethyl 2 g twice daily or placebo.
At 1 year, triglyceride levels in the fish oil group dropped by 18.3 percent but increased by 2.2 percent for placebo (p<0.001). LDL-cholesterol increased by 3.1 percent for fish oil but increased by 10.2 percent for placebo (p<0.001).
However, despite the reduction in other CV events, patients given fish oil were more likely to get hospitalized for atrial fibrillation or flutter (p=0.004) and numerically experienced more serious bleeding events (p=0.06). There was also no difference in heart failure rate between groups.
Another study on fish oil, the VITAL study, presented at AHA 2018 yielded negative results. Experts said patients are not going to get benefits from OTC fish-oil pills as only 300 mg of the 1,000 mg formulation is omega 3 that is known to keep heart healthy.