American Heart Association

American Heart Association

November 19, 2019
3 min read

Vitamin D, fish oil fail to reduce first HF hospitalization risk

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Luc Djoussé

PHILADELPHIA — Interventions with vitamin D or omega-3 failed to reduce rates of first heart failure hospitalization in a large cohort of healthy adults, although researchers observed a benefit for recurrent HF hospitalization with fish oil supplementation, according to findings from an ancillary study of the VITAL trial presented at the American Heart Association Scientific Sessions.

“We found that neither vitamin D nor omega-3 significantly reduced the rate for first heart failure hospitalization, but omega-3 supplementation resulted in a statistically significant 14% reduction in the rate of recurrent heart failure hospitalizations, our secondary endpoint, compared with placebo,” Luc Djoussé, MD, ScD, MPH, FAHA, associate epidemiologist at Brigham and Women's Hospital and associate professor of medicine at Harvard Medical School, told Healio. “Vitamin D3 supplements had no effect. Future trials are needed to confirm that omega-3 fatty acids reduce the rate of recurrent heart failure hospitalizations.”

As Healio previously reported, neither omega-3 nor vitamin D supplements for primary prevention reduced major CV events or development of invasive cancers compared with placebo over 5 years of follow-up in the large-scale VITAL trial, although investigators reported that some secondary endpoints showed promising signals.

The 25,871-patient, placebo-controlled, NIH-funded trial had a 2x2 factorial design, by which patients were randomly assigned vitamin D3 (cholecalciferol) 2,000 IU per day and omega-3 fatty acids 1 g per day, each compared with placebo. For the ancillary VITAL-HF analysis, primary outcome was first hospitalization for HF after randomization and recurrent hospitalization for HF was a prespecified secondary outcome. The ancillary study excluded 36 participants with prevalent HF.

Mean age at randomization was 67 years and 50.6% of participants were women.

During a median follow-up of 5.3 years, first HF hospitalization occurred in 499 participants, with 240 events in the vitamin D group and 259 events in the placebo group (HR = 0.93; 95% CI, 0.78-1.11). In the omega-3 group, HF hospitalization occurred in 244 in the omega-3 group and 255 in the placebo group (HR = 0.96; 95% CI, 0.8-1.14). Analyses restricted to 106 confirmed HF cases yielded similar results, with an HR of 1.12 (95% CI: 0.77-1.65) for vitamin D vs. placebo and 0.96 (95% CI, 0.66-1.41) for omega-3 fatty acids compared with placebo, Djoussé said.

In the secondary analysis, recurrent rates of HF hospitalization were not different between participants assigned vitamin D or placebo (341 vs. 364 events). However, researchers observed a 14% reduction in recurrent HF hospitalization with omega-3 supplementation compared with placebo (326 vs. 379 events; HR = 0.86; 95% CI, 0.74 to 0.998). Few events were preceded by MI, Djoussé said.


“There are no surprises here, since vitamin D intervention had no benefits on CV risk and kidney function as reported in the parent VITAL study and in another ancillary study,” Djoussé said. “In contrast, fish oil reduced the rate of MI in the parent VITAL [trial] and we know that MI can lead to heart failure.”

In an question-and-answer session following presentation of the results, Djoussé noted that the formulation of omega-3 used in VITAL — a blend of eicosapentaenoic acid (EPA) with docosahexaenoic acid (DHA) — was much different from the pharmaceutical grade icosapent ethyl (Vascepa, Amarin) used in the landmark REDUCE-IT study.

“This was a combination of 460 mg of EPA with DHA,” Djoussé said. “Those of you familiar with REDUCE-IT, where patients received 4 g, that is almost 10-fold higher than what we had in the VITAL ancillary study. There is plenty of evidence suggesting that, perhaps, EPA may have a little edge over DHA, but we don’t have a definite answer.” – by Regina Schaffer


Djoussé L, et al. Presentation MDP475. A Deeper Dive into Newer Therapies for Heart Failure II. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2019; Philadelphia.

Djousse L, et al. Circulation. 2019; doi:10.1161/CIRCULATIONAHA.119.044645.

Disclosure: Pharmavite LLC, Pronova BioPharma and BASF donated the study agents for VITAL. Djoussé reports he has received investigator-initiated grants from Amarin and

Merck. Please see the study for all other authors’ relevant financial disclosures.