Targeted vitamin D supplementation and major adverse cardiovascular events after myocardial infarction: the TARGET-D trial

BACKGROUND AND AIMS: Many observational studies have reported associations between low serum 25-hydroxyvitamin D [25(OH)D] levels and adverse cardiovascular (CV) outcomes. However, randomized trials have not demonstrated a reduction in CV events with vitamin D supplementation, potentially due to fixed or non-targeted dosing strategies. The aim of this study was to determine if targeted vitamin D management among myocardial infarction (MI) patients reduces CV events. METHODS: TARGET-D is a pragmatic randomized trial, where subjects were randomized to usual care or targeted vitamin D management between April 2017 and May 2023 (average follow-up 4.2 ± 2.0 years). The treatment arm received vitamin D3 supplementation and ongoing titration based on a dosing algorithm to reach and maintain a target 25(OH)D level of >40-80 ng/mL. TARGET-D concluded follow-up on 17 March 2025, when ≥104 primary outcome events (major adverse CV events: composite of death, MI, heart failure hospitalization, and stroke) occurred. RESULTS: Participants (n = 630) had a median age of 63 (interquartile range: 55-70) years and 78.1% were men. Baseline 25(OH)D levels were 25 (interquartile range: 18-33) ng/mL, with 87.0% ≤ 40 ng/mL, and 52.4% began vitamin D3 dosing at 5000 IU. Major adverse CV events did not achieve significance [vitamin D: 15.7% vs usual care: 18.4%; hazard ratio (HR) .85, 95% confidence interval .58-1.24, P = .40]. Among secondary endpoints, outcomes for vitamin D vs usual care were 8.9% vs 9.2% for death (HR .98, P = .95), 3.8% vs 7.9% for MI (HR .48, P = .03), 4.2% vs 3.5% for heart failure hospitalization (HR 1.21, P = .65), and 1.6% vs .9% for stroke (HR 1.69, P = .47). CONCLUSIONS: Prevalence of 25(OH)D insufficiency was high among MI patients. Targeted vitamin D supplementation and ongoing titration did not significantly reduce major adverse CV events.