Titrated vitamin D after myocardial infarction did not significantly cut cardiovascular events

Design

Pragmatic randomised trial, usual care vs algorithm-titrated vitamin D3, mean follow-up 4.2 years

Population

630 patients after myocardial infarction; median age 63 years; 87.0% had 25(OH)D at or below 40 ng/mL

Primary outcome

Major adverse cardiovascular events (death, MI, heart failure hospitalisation, stroke)

Effect

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

TARGET-D was a pragmatic randomised trial in 630 patients after myocardial infarction (median age 63 years, 78.1% men). The treatment arm received vitamin D3, with doses adjusted by an algorithm to reach and hold a 25-hydroxyvitamin D level of 40 to 80 ng/mL. Controls had usual care. Average follow-up was 4.2 years.

Baseline levels were low: median 25 ng/mL, and 87.0% were at or below 40 ng/mL. Major adverse cardiovascular events (death, MI, heart failure hospitalisation, stroke) occurred in 15.7% with vitamin D and 18.4% with usual care (HR 0.85, 95% CI 0.58 to 1.24, P = 0.40). Death was 8.9% vs 9.2%. Heart failure hospitalisation was 4.2% vs 3.5% and stroke 1.6% vs 0.9%, both with wide intervals.

Recurrent MI was 3.8% vs 7.9% (HR 0.48, P = 0.03), but that is a secondary endpoint in a trial whose primary result was null, and it should be treated as a hypothesis for testing. The trial ended once the target number of primary events had been reached.

• Do not start vitamin D after MI as a means of preventing cardiovascular events on this evidence.
• Treat deficiency on its own merits (bone health, symptoms), not as secondary prevention.
• Keep secondary prevention focused on antithrombotics, statins, blood pressure, rehabilitation and glucose control.
• Do not quote the recurrent-MI result as proof; it was a secondary finding.

Why it matters

It tests the idea that earlier vitamin D trials failed because dosing was fixed rather than titrated, and the answer is still not a clear yes.

Don't overread it

The recurrent-MI difference is a secondary endpoint and cannot be taken as a benefit; the primary result was not significant.

The statistics, in plain English

A hazard ratio of 0.85 with an interval of 0.58 to 1.24 is compatible with a 42% reduction, no effect or a 24% increase, so the trial could not settle the question. The recurrent-MI HR of 0.48 comes from one of several secondary endpoints; with multiple comparisons and a null primary result, a P of 0.03 is weak evidence.

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