CV Benefits of Vitamin D Capsules Suggested in Huge D-Health Trial

Adults aged 60 or over who have taken high monthly doses of Vitamin D for 5 years failed to show a significant reduction in risk of cardiovascular (CV) events overall, but may have benefited from other CV outcomes in an analysis of a large prospective randomized trial.

Risk reductions on vitamin D in the mixed population in primary and secondary prevention were small in absolute terms but reached a significant level of 19% in the case of myocardial infarction (MID).

Over 5 years, 6.6% of people in the placebo group had major CV events, the primary endpoint, compared with 6% in the vitamin D group. The difference, which was 5.8 fewer events per 1000 participants, was not significant in the adjusted analysis.

Yet vitamin D supplementation was associated with the potential benefit of MI and an 11% lower risk of coronary revascularization.

Additionally, a subgroup analysis hinted at a potentially reduced risk of a CV event due to vitamin D supplementation in people who participated in the trial on statins or other CV drugs in general.

“Most other studies have not found vitamin D benefits for major CV events,” said lead researcher Rachel E. Neale, PhD. theheart.org/Medscape Cardiology. Although there was a significant effect for MI, the difference in the composite primary endpoint was not significant, “in agreement with other studies”.

“However, the effects of myocardial infarction in people taking statins or cardiovascular disease medications at baseline suggest benefit,” said Neale, of the QIMR Berghofer Medical Research Institute, Queensland, Australia. Still, “it’s important to keep in mind that these may be incidental findings.”

The analysis based on the D-Health the study was published online June 28 at The BMJ.

Minimal benefits

The 21,302 patients in the trial, called D-Health and conducted in Australia from 2014 to 2020, were randomly assigned in a double-blind fashion to receive either a placebo or vitamin D.₃ supplements for 5 years planned. They were asked to take a placebo or one vitamin D capsule monthly, with each active capsule containing 60,000 IU of the vitamin.

People with self-reported hypercalcemia, hyperparathyroidism, kidney stones, osteomalaciaOr sarcoidosis, and those taking > 500 IU/day of vitamin D supplements were excluded from enrollment. Participants were aged 60 to 84 at the time of randomization and 46% were female.

With 80% of 10,658 participants assigned to vitamin D and 78% of 10,644 control subjects completing the 5-year intervention, 6% and 6.6%, respectively, achieved the primary endpoint of a major CV event, defined as MI, strokeor coronary revascularization.

The hazard ratio ( RR ) for an effect of vitamin D on the primary endpoint was 0.91 (95% CI 0.81, 1.01). The number needed to treat to prevent a major CV event was 172.

The RR for MI was 0.81 (95% CI, 0.67, 0.98), for coronary intervention was 0.89 (0.78, 1.01), and for stroke was 0.99 (0.80 – 1.23).

Adverse event rates were similar at around 16% in both groups and included hypercalcemia, kidney stones, gastrointestinal problems and rash.

Vitamin D in moderate doses has low toxicity, Neale said, “so I think it would be reasonable for clinicians to consider supplementing older people who have no contraindications, especially those with underlying risk factors for CV disease,” Neale said. But patients should be told that the evidence for such a recommendation is not strong, so they can make an informed decision, she added.

Also, in general, “we would be cautious about extrapolating to formulations other than those used in the study,” Neale said. “However, in this case, I think it would be reasonable to extrapolate to using 2000 IU per day orally, provided that the same compliance can be maintained for a long period of time.”

Chance finds?

Based on the current study and in light of previous research, “it is premature to specifically recommend vitamin D supplementation for the prevention of cardiovascular disease,” said Nour Makarem, PhD, of the Mailman School of Public Health. , Columbia University, New York. theheart.org/Medscape Cardiology.

“Previous clinical trials have not shown an association between vitamin D supplementation and cardiovascular events,” observed Makarem, not affiliated with the current study. Also, she agreed, he looked at “multiple results, which increases the likelihood that the results were due to chance.”

In addition, she said, the study authors observed a possible protective effect of vitamin D “in people who had enough vitamin D at baseline, but not among those who had insufficient vitamin D. It It is important to interpret this result with caution, as they used predicted, not measured, vitamin D status for these analyses.”

There is a need for studies in other populations, including younger people and “especially populations with higher rates of vitamin D deficiency,” Makarem observed. Additionally, further research should aim to “understand the interactions between vitamin D supplementation and cardiovascular medications, including statins.”

The D-Health trial is funded by project grants from the National Health and Medical Research Council. Neale was supported by NHMRC scholarships. Neither she nor Makarem reported relevant financial relationships.

BMJ. Posted June 28. Full Text

Follow Marilynn Larkin on Twitter: @MarilynL .

Learn more at heart.org | Medscape Cardiology, follow us on Twitter And Facebook