Vitamin D Dosing Tailored to Optimal Levels Reduced Risk of Recurrent MI by More Than Half

Data presented at the American Heart Association Scientific Sessions 2025 showed that targeted vitamin D supplementation did not reduce major adverse cardiovascular events (MACE) in adults with prior myocardial infarction (MI). However, individualized dosing was associated with a significantly lower risk of recurrent MI compared with usual care.^1,2

The TARGET-D randomized clinical trial enrolled 630 adults within the Intermountain Health system between April 2017 and May 2023 and followed participants for a mean of 4.2 years.^1,2

Participants had a mean age of 62.5 years, 78% were men, and all had sustained an MI within a month prior to enrollment. At baseline, 87% had serum 25-hydroxyvitamin D (25-[OH]D) concentrations of 40 ng/mL or lower, according to the study abstract.^1,2

Individualized Dosing: New Approach

The trial was designed to address limitations of earlier vitamin D studies that used fixed-dose regimens without establishing or achieving therapeutic serum targets. “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. "We took a different approach," principal investigator Heidi T. May, PhD, MSPH, an epidemiologist and professor of research at Intermountain Health, explained in a statement.³ "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.”³

Individuals randomized to targeted supplementation underwent a protocolized dosing strategy^1,2:

• If baseline 25-(OH)D was greater than 40 ng/mL, no supplementation was initiated and annual reassessment was performed.
• If baseline leve was 40 ng/mL or lower, vitamin D₃ supplementation was started and the participant was reassessment every 3 months until the target was achieved, after which monitoring shifted to annual intervals.

Based on this algorithm:

• 7.4% of participants required no supplementation,
• 36.3% required 1,000–4,000 IU/day
• 56.3% required 5,000 IU/day or more, substantially higher than the FDA-recommended daily intake of 800 IU

Approximately 60% of participants in the treatment arm achieved their target level by 3 months; median time to target was 5.2 months, and 21% never achieved a level above 40 ng/mL.^1,2

Primary Endpoints and Outcomes

The primary endpoint was time to first MACE (all-cause death, MI, stroke, or heart failure hospitalization). A safety endpoint tracked the development of kidney stones.

Kidney stone incidence did not differ between the treatment and usual-care groups (6.8% vs 6.6%; HR = 1.04; log-rank P = .96). Similarly, the primary endpoint showed no statistically significant difference:

• Intention-to-treat analysis:
  • MACE: 15.7% (supplementation) vs 18.4% (usual care)
  • HR = 0.85 (95% CI, 0.58–1.24); log-rank P =.40
• Per-protocol analysis (restricted to participants who achieved >40 ng/mL):
  • MACE: 11.3% vs 18.4%
  • HR = 0.74 (95% CI, 0.47–1.17); log-rank P =.14

No significant differences were seen in individual components—death, stroke, or heart failure hospitalization—although death rates were numerically lower in the per-protocol cohort.^1,2

Risk of Recurrent MI Reduced by Half

In contrast, the secondary endpoint of recurrent MI demonstrated a statistically significant benefit in the intention-to-treat population^1,2:

• Intention-to-treat:
  • MI: 3.8% (supplementation) vs 7.9% (usual care)
  • HR = 0.48 (95% CI, 0.24–0.96); log-rank P =.03
• Per-protocol:
  • MI: 4% vs 7.9%
  • HR = 0.69 (95% CI, 0.33–1.44); log-rank P =.15

Among the study limitations May et al acknowledged a modest sample size, limited racial and ethnic diversity (approximately 90% self-identified as White), and restriction to adults with established cardiovascular disease, which may limit generalizability to broader populations.³

Potential for Patient Management

The TARGET-D findings reinforce the feasibility of achieving targeted serum vitamin D concentrations through individualized dosing and suggest potential benefit for recurrent MI risk reduction within secondary-prevention populations, authors suggested in a statement. May noted that the results may have implications for patient management, stating, “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.”³

Study investigators also emphasized that additional clinical trials are needed to determine whether targeted vitamin D supplementation could play a role in primary prevention before a first cardiac event.²

References

1. 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. Abstract presented at: American Heart Association Scientific Sessions; November 7-10, 2025; New Orleans. Accessed November 11, 2025. https://news.intermountainhealth.org/targeted-vitamin-d3-supplementation-cuts-risk-of-heart-attack-patients-having-a-second-heart-attack-in-half-intermountain-study-shows/
2. Targeted vitamin D3 supplementation cuts risk of heart attack patients having a second heart attack in half, Intermountain study shows. News release. Intermountain Health. November 9, 2025. Accessed November 11, 2025.
3. Heart attack risk halved in adults with heart disease taking tailored vitamin D doses. News release. American Heart Association. November 9, 2025. Accessed November 11, 2025. https://newsroom.heart.org/news/heart-attack-risk-halved-in-adults-with-heart-disease-taking-tailored-vitamin-d-doses