Effect of vitamin D on all-cause mortality in heart failure (EVITA): a 3-year randomized clinical trial with 4000 IU vitamin D daily

Eur Heart J. 2017 Aug 1;38(29):2279-2286. doi: 10.1093/eurheartj/ehx235.

Abstract

Aims: Circulating 25-hydroxyvitamin D (25OHD) levels <75 nmol/L are associated with a nonlinear increase in mortality risk. Such 25OHD levels are common in heart failure (HF). We therefore examined whether oral vitamin D supplementation reduces mortality in patients with advanced HF.

Methods and results: Four hundred HF patients with 25OHD levels <75 nmol/L were randomized to receive 4000 IU vitamin D daily or matching placebo for 3 years. Primary endpoint was all-cause mortality. Key secondary outcome measures included hospitalization, resuscitation, mechanical circulatory support (MCS) implant, high urgent listing for heart transplantation, heart transplantation, and hypercalcaemia. Initial 25OHD levels were on average <40 nmol/L, remained around 40 nmol/L in patients assigned to placebo and plateaued around 100 nmol/L in patients assigned to vitamin D. Mortality was not different in patients receiving vitamin D (19.6%; n = 39) or placebo (17.9%; n = 36) with a hazard ratio (HR) of 1.09 [95% confidence interval (CI): 0.69-1.71; P = 0.726]. The need for MCS implant was however greater in patients assigned to vitamin D (15.4%, n = 28) vs. placebo [9.0%, n = 15; HR: 1.96 (95% CI: 1.04-3.66); P = 0.031]. Other secondary clinical endpoints were similar between groups. The incidence of hypercalcaemia was 6.2% (n = 10) and 3.1% (n = 5) in patients receiving vitamin D or placebo (P = 0.192).

Conclusion: A daily vitamin D dose of 4000 IU did not reduce mortality in patients with advanced HF but was associated with a greater need for MCS implants. Data indicate caution regarding long-term supplementation with moderately high vitamin D doses.

Trial registration information: clinicaltrials.gov Idenitfier: NCT01326650.

Keywords: Calcium; Heart failure; Hypercalcaemia; Mechanical circulatory support; Mortality; Randomized clinical trial; Survival; Vitamin D.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Cardiomyopathy, Dilated / complications
  • Cardiomyopathy, Dilated / mortality
  • Cause of Death
  • Dietary Supplements
  • Female
  • Heart Failure / diet therapy*
  • Heart Failure / mortality
  • Heart Transplantation / mortality
  • Heart Transplantation / statistics & numerical data
  • Heart-Assist Devices / statistics & numerical data
  • Hospitalization / statistics & numerical data
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Ischemia / complications
  • Myocardial Ischemia / mortality
  • Prospective Studies
  • Risk Factors
  • Treatment Outcome
  • Vitamin D / administration & dosage*
  • Vitamin D / analogs & derivatives
  • Vitamin D / metabolism
  • Vitamin D Deficiency / diet therapy
  • Vitamins / administration & dosage*

Substances

  • Vitamins
  • Vitamin D
  • 25-hydroxyvitamin D

Associated data

  • ClinicalTrials.gov/NCT01326650