VITAL and REDUCE-IT—both highly anticipated trials revolving around the cardiovascular benefits of fish oil products—delivered mixed results at this year’s AHA Scientific Sessions in Chicago, with one trial observing few heart benefits from omega-3s while the other saw a 25 percent reduction in major cardiovascular events with a purified eicosapentaenoic acid (EPA) product.
The latter study, REDUCE-IT, was heralded as a major success for EPAs in the prevention of heart disease. Led by Deepak Bhatt, MD, MPH, of Brigham and Women’s Hospital in Boston, the trial studied the efficacy of icosapent ethyl (known commercially as Vascepa) in more than 8,000 adults with or at risk for CVD.
Bhatt’s team sliced their study population in half: a primary prevention cohort that included those with established CVD and a secondary prevention cohort that consisted of patients with diabetes and at least one other cardiovascular risk factor. All participants were 45 or older, had fasting triglyceride levels between 150 and 500 mg/dL and took statins to control their high LDL-cholesterol.
After around five years of patients taking a 4-gram-per-day dose of icosapent ethyl, Bhatt et al. noted a 25 percent composite reduction in adverse cardiovascular events, including a 31 percent lowered risk of heart attack, a 28 percent reduced risk of stroke and a 20 percent reduction in cardiovascular death.
Bhatt said the trial saw low complication rates, though patients did experience a non-statistically significant increase in serious bleeding and a “small but significant” increase in atrial fibrillation.
“It’s unclear whether that’s a true concerning safety signal or chance, but definitely merits further evaluation,” Pradeep Natarajan, MD, who was uninvolved in the study, told Cardiovascular Business. “If we can help identify the patients who are more likely to get atrial fibrillation with this medicine that would be helpful, but I think there’s lots of outstanding questions about whether that’s a real safety concern.”
Natarajan, the director of preventive cardiology at Massachusetts General Hospital, said he was somewhat disappointed by the low proportion of women in the trial. Bhatt, too, admitted some of his study’s limitations, including the fact that he couldn’t comment on the cost-effectiveness or mechanisms of benefit in the trial.
Still, Natarajan said REDUCE-IT expands treatment options for a more unique subset of CVD patients with hypertriglyceridemia.
“I think [it] provides a great additional tool to specifically treat those patients,” he said. “And I like that general approach because kind of everybody we’re giving aspirin and statins, and this is much more of a precision medicine approach.”
VITAL results, on the other hand, presented by JoAnn Manson, MD, DrPH, of Harvard Medical School, elicited a more modest reaction. VITAL, a nationwide randomized trial that ran for just over five years, tested the utility of marine omega-3 fatty acids and vitamin D3 supplementation in the primary prevention of cardiovascular disease and cancer in 25,871 Americans.
Manson emphasized the diversity of her team’s trial, which included 5,106 black patients, and noted VITAL is the first large-scale randomized fish oil study to assess primary prevention in a usual-risk group of patients. The trial was placebo-controlled and randomized its thousands of patients to daily supplementation with either 2,000 IUs of vitamin D3 or 1 gram of an omega-3.
At follow-up, Manson and her colleagues found that omega-3s seemed to be linked more to cardiovascular benefits, while vitamin D3 correlated more with cancer outcomes.
She said omega-3 supplementation was associated with a small but statistically insignificant 8 percent reduction in the study’s primary endpoint of major CVD events—a composite of myocardial infarction, stroke and cardiovascular mortality. The fatty acids were also linked to a 28 percent decreased likelihood of MI.
There weren’t significant reductions in extended endpoints like bypass surgery or angioplasty, but Manson et al. found that, in secondary analyses, omega-3s were associated with a 22 percent reduced risk of PCI, 17 percent reduced risk of total heart disease and 50 percent reduced risk of fatal MI.
“But these findings, in particular, should be interpreted with caution,” Manson said.
Subgroup analyses found patients who generally consumed the least amount of fish (less than a serving and a half per week) saw the greatest benefit from omega-3 supplementation, with a 40 percent lowered risk of heart attack. Black patients, as well, saw great benefit, reaching a 77 percent reduced risk of adverse CVD events.
Vitamin D didn’t do much for cardiovascular risk in the study, but Manson said her team found some oncologic benefit after studying patients’ baseline blood levels.
“In terms of cancer, this is where we did see a signal,” she said. “In the overall follow-up period of a median 5.3 years we saw no significant reduction in cancer or cancer death, but it was edging toward reduction for cancer death.”
That reduction ended up being 25 percent—a statistically significant drop.
Jane Armitage of the University of Oxford lauded Manson’s team for their strong adherence to interventions and the trial’s balance between patient groups. The fact that neither omega-3s nor vitamin D3 significantly reduced the study’s primary endpoints of major CVD or total invasive cancer was a robust result, she said.
Armitage said physicians should focus more on that statistic than the fact that omega-3s significantly reduced MI risk.
“I think these results need to be seen as hypothesis-generating,” she said. “I think they’re very interesting, but I think that we need to be cautious in our interpretation.”