Effect of Vitamin D on all-causemortality in heart failure (EVITA): A 3-year randomized clinical trial with 4000 IU Vitamin D daily

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.