LOS ANGELES – Oral vitamin D3 may have a future as adjunctive therapy in patients with heart failure, according to Dr. Rebecca S. Boxer.
Six months of oral vitamin D3 therapy at 50,000 IU/wk resulted in a 37% decrease in serum aldosterone level in a randomized, double-blind, placebo-controlled trial conducted in vitamin D–deficient patients with heart failure.
Moreover, parathyroid hormone levels, which were elevated at baseline, fell by 41% in the active treatment arm, she reported at the annual scientific sessions of the American Heart Association.
The study involved 64 patients with New York Heart Association class II-IV heart failure, all having a baseline serum vitamin D level below 20 ng/mL. All participants were on maximum tolerated doses of standard heart failure medications. The patients were randomized to oral vitamin D3 at 50,000 IU/wk plus 400 mg of calcium citrate twice daily for 6 months or to calcium plus placebo.
Mean serum vitamin D levels climbed from 19 ng/mL to 60 ng/mL in treated patients while remaining unchanged over time in controls.
Serum aldosterone levels fell from 10.0 ng/mL to 6.3 ng/dL in the active treatment group and remained static in controls. The mean serum parathyroid hormone level dropped from 62.3 pg/mL to 37.1 pg/mL with vitamin D therapy but stayed steady in controls, said Dr. Boxer of Case Western Reserve University, Cleveland.
The primary endpoint in this randomized trial was change in aerobic capacity; vitamin D supplementation had no effect on this endpoint. Nor did it have any significant impact on heart failure symptoms, echocardiographic findings, body weight, blood pressure, serum renin, or C-reactive protein levels in this relatively small study.
Nonetheless, the finding of a moderate reduction in serum aldosterone level indicates that the effects of vitamin D3 on the renin-angiotensin-aldosterone system (RAAS) in patients with heart failure warrants further study, including assessment of possible long-term clinical benefit.
Dr. Boxer pointed out that serum aldosterone level in patients with heart failure predicts mortality. And aldosterone blockade with an aldosterone antagonist has been shown to improve clinical outcomes in heart failure patients with a depressed left ventricular ejection fraction in RALES, the Randomized Aldactone Evaluation Study (N. Engl. J. Med. 1999;341:709-17) and EPHESUS, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (N. Engl. J. Med. 2003;348:1309-21). Aldosterone blockade is also actively under study in heart failure patients with preserved systolic function in the ongoing TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) study, due to report results next year.
"There may be certain patient groups that could greatly benefit from vitamin D3 therapy, particularly patients who may not be able to tolerate RAAS blockade or those who have aldosterone escape," she said.
The mechanism by which oral vitamin D3 reduces serum aldosterone is unknown. The mechanism is clearly non–renin-dependent, given that serum renin level remained unchanged. In vitro studies suggest that vitamin D might act through a direct effect on steroidogenesis in adrenal cortical cells, Dr. Boxer said.
The study was funded by the American Heart Association. Dr. Boxer reported having no relevant financial conflicts.