Target-D: Optimized Vitamin D Dosage Reduces Risk of Myocardial Infarction in Heart Disease Patients

Adults with acute coronary syndrome (ACS) and a history of myocardial infarction who took vitamin D doses specifically tailored to reach optimal blood levels saw their risk of another heart attack reduced by >50% compared to those without vitamin D optimization, based on the Target-D study.1

Based on data presented at the American Heart Association’s Scientific Sessions 2025 in New Orleans, Louisiana, by Heidi May, PhD, an epidemiologist at Intermountain Heart Institute, this study emphasizes the potential therapeutic value of monitoring vitamin D levels and tailoring doses.

“Previous clinical trial research on vitamin D tested the potential impact of the same vitamin D dose for all participants without checking their blood levels first,” May said in a statement. “We took a different approach. We checked each participant’s vitamin D levels at enrollment and throughout the study, and we adjusted their dose as needed to bring and maintain them in a range of 40-80 ng/mL.”1

Target-D was a randomized clinical trial investigating whether achieving vitamin D levels >40 ng/mL among patients with ACS. A total of 4269 patients were initially screened for inclusion; of these, 3108 were excluded due to the following criteria, among others:

• Did not undergo angiography for an MI within the past month (n = 855)
• Did not receive follow-up (n = 862)
• Hypersensitivity to vitamin D (n = 6)
• Vitamin D supplementation of >1000 RJ daily for >40% of the days in the last 3 months (n = 675)
• Systemic disease with a reduced life expectancy (n = 56)
• Hypercalcemia (n = 2)
• History of psychiatric illness/condition which would interfere with the ability to understand or complete the study’s requirements (n = 418).2

Ultimately, 630 patients were randomly assigned in a 1:1 ratio to either standard of care, who did not receive vitamin D management, or tailored vitamin D supplementation, with doses adjusted every 3 months until vitamin D blood levels reached >40 ng/mL. After reaching this threshold, levels were checked annually, and doses were adjusted if vitamin D levels dropped below 40 ng/mL.2

Investigators noted a primary endpoint of time to major adverse cardiovascular events (MACE); this did not achieve statistical significance in the intention-to-treat analysis. A total of 107 MACEs, including myocardial infarction, heart failure hospitalization, stroke, or death, occurred during the study, with 15.7% in the treatment group and 18.4% in the standard care group.2

However, the component of follow-up myocardial infarction was substantially reduced in the treatment arm (7.9% versus 3.8%, log-rank P = .03). In a per-protocol analysis, although still not statistically significant, May and colleagues found clinically relevant risk reductions for MACE, death, and myocardial infarction when achieving and maintaining vitamin D levels >40 ng/mL.1

Despite these outcomes, investigators noted a few limitations. The trial exclusively included patients with a diagnosis of heart disease, meaning the results may not apply to those without. Additionally, the trial involved a relatively small number of participants, eliminating the possibility of a more complete analysis of other conditions and outcomes.2

Before altering or adding a vitamin regimen, the AHA and the trial investigators encourage patients to consult with their cardiologist.1

“We encourage people with heart disease to discuss vitamin D blood testing and targeted dosing with their health care professionals to meet their individual needs,” May said in a statement.1

References

1. Ebert A. Heart attack risk halved in adults with heart disease taking tailored vitamin D doses. heart.org. November 9, 2025. Accessed November 10, 2025. https://newsroom.heart.org/news/heart-attack-risk-halved-in-adults-with-heart-disease-taking-tailored-vitamin-d-doses

2. May H, Le V, Anderson J, et al. A Randomized Clinical Trial Evaluating Vitamin D Normalization on Major Adverse Cardiovascular-Related Events Among Acute Coronary Syndrome Patients: The TARGET-D Trial. Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.