Vitamin D and Omega-3 Trial - VITAL

Nov 13, 2020
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Presenter/Author:
JoAnn Elisabeth Manson, MD, PhD
Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
National Institutes of Health. Pharmavite donated vitamin D and Pronova, while BioPharma and BASF donated fish oil (Omacor) (or matching placebo).
Date Presented:
11/13/2020
Date Published:
11/12/2019
Date Updated:
11/13/2020
Original Posted Date:
11/10/2018
References

Contribution To Literature:

The VITAL trial showed that supplementation with either n–3 fatty acid at a dose of 1 g/day or vitamin D3 at a dose of 2000 IU/day was not effective for primary prevention of CV or cancer events among healthy middle-aged men and women over 5 years of follow-up.

Description:

The goal of the trial was to assess the cardiovascular (CV) and cancer benefits of n–3 (also called omega-3) fatty acid and vitamin D3 supplementation compared with placebo among healthy participants.

Study Design

In a 2 x 2 factorial design, healthy participants were randomized in a 1:1 fashion to either vitamin D3 (at a dose of 2000 IU per day) (n = 12,927) or placebo (n = 12,944), or n–3 fatty acids (1 g per day as a fish-oil capsule containing 840 mg of n–3 fatty acids, including 460 mg of eicosapentaenoic acid [EPA] and 380 mg of docosahexaenoic acid [DHA]) (n = 12,933) or matching placebo (n = 12,938).

  • Total number of enrollees: 25,871
  • Duration of follow-up: 5.3 years
  • Mean patient age: 67.1 years
  • Percentage female: 51%

Inclusion criteria:

  • Men >50 years or women >55 years
  • No known cardiovascular disease or cancer

Exclusion criteria:

  • Renal failure or dialysis
  • Cirrhosis
  • History of hypercalcemia

Other salient features/characteristics:

  • African American: 20%
  • Mean body mass index: 28 kg/m2
  • Diabetes: 13.7%

Principal Findings:

The primary CV outcome of CV death, nonfatal myocardial infarction (MI), or stroke, for vitamin D3 vs. placebo, was 3.1% vs. 3.2%, hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.85-1.1, p = 0.69.

  • CV death: 1.2% vs. 1.1%, for vitamin D3 vs. placebo, respectively
  • Stroke: 1.1% vs. 1.2%
  • MI: 1.3% vs. 1.4%
  • Primary cancer outcome, invasive cancer: 6.1% vs. 6.4%, HR 0.96, 95% CI 0.88-1.06, p = 0.47

The primary CV outcome of CV death, nonfatal MI, or stroke, for n–3 fatty acid vs. placebo, was 3.0% vs. 3.2%, HR 0.92, 95% CI 0.80-1.06, p = 0.24.

  • CV death: 1.1% vs. 1.1%, for n–3 fatty acid vs. placebo, respectively
  • Stroke: 1.1% vs. 1.1%
  • MI: 1.1% vs. 1.5%, HR 0.72, 95% CI 0.59-0.90
  • Primary cancer outcome, invasive cancer: 6.3% vs. 6.2%, HR 1.03, 95% CI 0.93-1.13, p = 0.56

Secondary outcomes for vitamin D3 vs. placebo:

  • All-cause mortality: 3.8% vs. 3.8%

Secondary outcomes for n–3 fatty acid vs. placebo:

  • Total coronary heart disease: 0.3% vs. 0.4%
  • All-cause mortality: 3.8% vs. 3.7%

VITAL-CKD: Nested within the VITAL trial, VITAL-CKD sought to assess progression or development of chronic kidney disease (CKD) in patients with type 2 diabetes (n = 1,312). Mean change in estimated glomerular filtration rate from baseline to year 5:

  • Vitamin D3 vs. placebo:  −12.3 vs. −13.1 ml/min/1.73 m2 (difference, 0.9 [95% CI, −0.7 to 2.5] ml/min/1.73 m2)
  • Omega-3 fatty acid vs. placebo: −12.2 vs. −13.1 ml/min/1.73 m2 (difference, 0.9 [95% CI, −0.7 to 2.6] ml/min/1.73 m2)
  • There was no significant interaction between the two interventions.

VITAL Rhythm: Atrial fibrillation (AF) ascertainment was done by questionnaire. Patients were required to provide permission to review Centers for Medicare & Medicaid Services claims data for AF. AF events were subsequently confirmed by medical record review. Over 5.3 years, 3.6% developed incident AF. There was no difference in AF between omega-3 fatty acid vs. placebo (469 vs. 431, HR 1.09, 95% CI 0.96-1.24, p = 0.19) or vitamin D3 vs. placebo (HR 1.09, 95% CI 0.96-1.25, p = 0.19).

Interpretation:

The results of this trial indicate that supplementation with either n–3 fatty acid at a dose of 1 g/day or vitamin D3 at a dose of 2000 IU/day was not effective for primary prevention of CV or cancer events among healthy middle-aged men and women over 5 years of follow-up. There was also no difference in progression/development of CKD among patients with type 2 diabetes. This is one of the largest trials on this topic. The finding of a lower MI risk with n–3 fatty acid is hypothesis generating and deserves further study. The authors also noted some interaction with baseline fish consumption, with greater CV benefit observed among participants who had low fish intake at baseline.

References:

Presented by Dr. Christine M. Albert at the American Heart Association Virtual Scientific Sessions, November 13, 2020.

De Boer IH, Zelnick LR, Ruzinski J, et al. Effect of Vitamin D and Omega-3 Fatty Acid Supplementation on Kidney Function in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA 2019;322:1899-1909.

Manson JE, Cook NR, Lee IM, et al., on behalf of the VITAL Research Group. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med 2019;380:33-44.

Manson JE, Cook NR, Lee IM, et al., on behalf of the VITAL Research Group. Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med 2019;380:23-32.

Editorial: Keaney JF Jr, Rosen CJ. VITAL Signs for Dietary Supplementation to Prevent Cancer and Heart Disease. N Engl J Med 2019;380:91-3.

Presented by Dr. JoAnn E. Manson at the American Heart Association Annual Scientific Sessions (AHA 2018), Chicago, IL, November 10, 2018.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins

Keywords: AHA Annual Scientific Sessions, AHA18, Cholecalciferol, Coronary Disease, Docosahexaenoic Acids, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Fish Oils, Middle Aged, Myocardial Infarction, Neoplasms, Primary Prevention, Stroke, Vitamin D, Diabetes Mellitus, Type 2


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