Effect of Simvastatin/Ezetimibe 10/10 mg Versus Simvastatin 40 mg on Serum Vitamin D Levels

Backround: Low levels of 25-hydroxyvitamin D (25(OH)VitD) have been recognized as an emerging cardiovascular disease (CVD) risk factor. Statins are reported to increase 25(OH)VitD concentration. Animal studies suggest that ezetimibe is a moderate inhibitor of intestinal 25(OH)VitD absorption, but its effect in humans is unknown. Aim: To investigate whether combined treatment with simvastatin/ezetimibe 10/10 mg would increase 25(OH)VitD levels compared to simvastatin 40 mg monotherapy in patients with primary hypercholesterolemia. Methods: In a Prospective Randomized Open-label Blinded End point study, 50 patients with primary hypercholesterolemia received either simvastatin/ezetimibe 10/10 mg (n=25) or simvastatin 40 mg (n=25) daily for 3 months. The primary end point was between-group difference in the change of serum25(OH)VitD levels. Results: Simvastatin/ezetimibe 10/10 mg was associated with a 36.7% increase in 25(OH)VitD serum levels (from 6.8 to 9.3 ng/mL, P=.000), while simvastatin 40 mg was associated with a 79.1% increase (from 6.7 to 12.0 ng/mL, P=.008). The increase in 25(OH)VitD levels in the simvastatin 40 mg group was significantly greater compared to that in the simvastatin/ezetimibe 10/10 mg group (P=.04). Both groups exhibited similar reductions in low-density lipoprotein cholesterol (LDL-C) levels. Conclusion: For similar LDL-C lowering simvastatin 40 mg is associated with greater increase in 25(OH)VitD compared to simvastatin/ezetimibe 10/10 mg. Whether this difference is relevant in terms of CVD risk reduction is unknown.