Titrating vitamin D to target after MI did not reduce major cardiovascular events

Design

Pragmatic randomised controlled trial, open-label, mean follow-up 4.2 years

Population

630 patients after myocardial infarction, median 25(OH)D 25 ng/mL

Primary outcome

MACE: death, MI, heart failure hospitalisation, stroke

Effect

15.7% vs 18.4%; HR 0.85 (95% CI 0.58–1.24), P = 0.40

TARGET-D was a pragmatic randomised trial of 630 patients after myocardial infarction (median age 63, 78% men). The intervention arm received vitamin D3, titrated by algorithm to keep serum 25(OH)D above 40 ng/mL (up to 80); the control arm had usual care. Mean follow-up was 4.2 years.

Insufficiency was common: median baseline 25(OH)D was 25 ng/mL and 87% were at or below 40. Yet major adverse cardiovascular events (death, MI, heart failure admission, stroke) occurred in 15.7% with vitamin D against 18.4% with usual care (HR 0.85, 95% CI 0.58 to 1.24, P = 0.40). Death was identical (8.9% vs 9.2%). Recurrent MI was lower (3.8% vs 7.9%, HR 0.48, P = 0.03), but this was one of several secondary endpoints.

The trial was designed to answer the criticism that earlier vitamin D trials failed because of fixed, non-targeted dosing. Titrating to a level did not change the primary result. It is small, open-label and underpowered for secondary outcomes, so the MI signal is a question for a larger trial, not a reason to prescribe.

• Do not add vitamin D after MI to reduce cardiovascular events; the primary endpoint was neutral.
• Low vitamin D after MI is common and can be treated for bone health, but not as cardiac therapy.
• The lower recurrent-MI rate is a secondary finding from a small trial and should not guide prescribing.
• Spend the consultation on statin intensity, antiplatelet adherence, blood pressure and smoking instead.

Why it matters

Targeted dosing was a leading remaining argument for vitamin D as cardiovascular therapy, and in this trial it did not hold up.

Don't overread it

The halved recurrent-MI rate is a secondary endpoint in a small trial and does not establish benefit.

The statistics, in plain English

The hazard ratio of 0.85 has a 95% confidence interval from 0.58 to 1.24, which crosses 1.0; the data fit anything from a 42% reduction to a 24% increase, so no benefit is shown. The recurrent-MI result (P = 0.03) is one of four secondary comparisons in a trial of 630 people; with that many looks, a chance finding is plausible.

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