Open Access

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

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Date: 12 May 2017
Journal: European Heart Journal , Volume 38 , Issue 29 , Pages 2279 - 2286
Topic: HEART FAILURE, Chronic Heart Failure
Authors: A. Zittermann , J. Ernst , S. Prokop , U. Fuchs , J. Dreier , J. Kuhn , C. Knabbe , I. Birschmann , U. Schulz , H. Berthold , S. Pilz , I. Gouni-Berthold , J. Gummert , M. Dittrich , J. Börgermann

ESC Journals

AbstractAims

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.

About the contributors

Armin Zittermann

Role: Author

Jana B. Ernst

Role: Author

Sylvana Prokop

Role: Author