A race-specific interaction between vitamin K status and statin use

Authors: KELLY, JENNIFER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; HARSHMAN, STEPHANIE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BRENSINGER, COLLEEN - University Of Pennsylvania; BARGER, KATHRYN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; KIMMEL, STEPHAN - University Of Pennsylvania; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Annals of Medicinal Chemistry and Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/16/2017
Publication Date: 8/18/2017
Citation: Kelly, J.M., Harshman, S.G., Brensinger, C.M., Barger, K., Kimmel, S.E., Booth, S.L. 2017. A race-specific interaction between vitamin K status and statin use. Annals of Medicinal Chemistry and Research. 3(1):1019.

Interpretive Summary: The oral anticoagulant warfarin is a vitamin K antagonist. Phylloquinone, the primary circulating form of vitamin K, is transported by triglyceride-rich lipoproteins and shares a metabolic pathway with cholesterol. Thus, there is biological plausibility for an interaction between serum phylloquinone and lipid-lowering medications (statins) in warfarin therapy. The objective of this study was to examine if serum phylloquinone and statin treatment interact during the initiation period of anticoagulation treatment in African Americans and Caucasians participating in the International Normalized Ratio Adherence and Genetics II cohort. Outcomes used to evaluate the potential interaction were: (1) the time to achieve stability in oral anticoagulation; and (2) the percent time in the therapeutic range achieved through stable anticoagulation. Among Caucasians taking statins, those who had average serum phylloquinone concentrations took longer to achieve anticoagulation stability than those who have very high or very low serum phylloquinone concentrations. The time required to achieve stable oral anticoagulation did not differ between any quartiles among Caucasians not taking statins. In African Americans, serum phylloquinone was not associated with the time to achieve oral anticoagulant stability, regardless of statin use. Serum phylloquinone and statin use were not associated significantly with the percent time in therapeutic range in either race. In conclusion, race may be an consideration in this diet-drug-drug interaction. Future studies are warranted to validate these findings and clarify the clinical relevance.

Technical Abstract: The oral anticoagulant warfarin is a vitamin K antagonist. Phylloquinone, the primary circulating form of vitamin K, is transported by triglyceride-rich lipoproteins and shares a metabolic pathway with cholesterol. Thus, there is biological plausibility for an interaction between serum phylloquinone and lipid-lowering medications (statins) in warfarin therapy. The objective of this study was to examine if serum phylloquinone and statin treatment interact during the initiation period of anticoagulation treatment in African Americans and Caucasians participating in the 2009-2013 International Normalized Ratio Adherence and Genetics II cohort. In a race-specific, cross-sectional analysis, the primary exposures were serum phylloquinone and statin use. Outcomes included days to maintenance and percent time in the therapeutic range (PTTR). A significant interaction between serum phylloquinone quartile and statin use with respect to days to maintenance was detected in Caucasians only (p=0.04). In Caucasians taking statins, those in the second and third serum phylloquinone quartiles reached maintenance 91% (HR=0.09, 95% CI 0.03-0.35) and 83% (HR=0.17, 95% CI 0.05-0.54) slower, respectively, compared to those in the lowest quartile. Days to maintenance did not differ between any quartiles among Caucasians not taking statins. In African Americans, serum phylloquinone was not associated with days to maintenance regardless of statin use. Serum phylloquinone and statin use were not associated significantly with PTTR in either race. In conclusion, race may be an important consideration in this diet-drug-drug interaction. Future studies are warranted to validate these findings and clarify the clinical relevance.