European Heart JournalTargeted Vitamin D Supplementation and Major Adverse Cardiovascular Events After Myocardial Infarction: The TARGET-D Trial

Observational studies have long linked low vitamin D levels with adverse cardiovascular outcomes, but prior supplementation trials have largely failed to demonstrate cardiovascular benefit. The TARGET-D trial tested whether a different strategy, individualized vitamin D₃ supplementation with dose titration to achieve serum 25-hydroxyvitamin D levels of 40 to 80 ng/mL, could improve outcomes after myocardial infarction. In this pragmatic randomized trial of 630 MI patients followed for a mean of 4.2 years, targeted vitamin D management did not significantly reduce the composite endpoint of major adverse cardiovascular events (MACE), despite a high prevalence of baseline vitamin D insufficiency.

Clinical Considerations

• 630 post-MI patients were randomized to targeted vitamin D management or usual care and followed for 4.2 ± 2.0 years.
• Baseline vitamin D insufficiency was common, with 87.0% of participants exhibiting 25(OH)D levels ≤40 ng/mL.
• The primary endpoint of MACE occurred in 15.7% of the vitamin D group versus 18.4% of usual care (HR 0.85; 95% CI 0.58–1.24; P=.40), failing to reach statistical significance.
• All-cause mortality was similar between groups (8.9% vs 9.2%; HR 0.98; P=.95).
• A secondary analysis showed fewer recurrent MI events with vitamin D supplementation (3.8% vs 7.9%; HR 0.48; P=.03), but this finding should be interpreted cautiously given the neutral primary endpoint.
• Heart failure hospitalization and stroke rates were not significantly different between treatment groups.

Practice Applications

• Recognize that correcting vitamin D insufficiency after MI did not significantly reduce overall MACE in this randomized trial.
• Interpret observational associations between low vitamin D levels and cardiovascular risk as distinct from evidence supporting supplementation for event reduction.
• Avoid using vitamin D supplementation solely for secondary cardiovascular prevention based on current evidence.
• Consider vitamin D replacement when clinically indicated for established non-cardiovascular indications rather than for proven reduction of cardiovascular events.
• Monitor future studies exploring whether specific patient subgroups derive cardiovascular benefit from targeted vitamin D strategies.