Ezetimibe may enhance and stabilize the effects of warfarin especially in patients taking statins, a new study published in Heart & Vessels has reported.
Ezetimibe, a cholesterol absorption inhibitor, lowers plasma low-density lipoprotein cholesterol (LDL-C) by inhibiting Niemann-Pick C1-like protein (NPC1L1). This protein is known to play an important role in absorption of vitamin K and other fat-soluble vitamins.
Researchers from Kitasato University School of Medicine, conducted a study to see whether add-on ezetimibe affected anticoagulation effects in patients taking warfarin. Ezetimibe was administered to 101 outpatients who were already on warfarin for anticoagulation between October 2007 and March 2015. Patients’ blood lipid levels, prothrombin time international normalized ratio (PT-INR) and time in therapeutic INR range (TTR) were analyzed.
Study data showed 70% of patients had an increase in PT-INR after adding ezetimibe (1.96±0.45 to 2.20±0.61; P<0.001). Nine patients required a reduction in warfarin dose according to their clinical indication. Researchers observed a positive correlation between PT-INR changes and statin use at baseline (P=0.03). Patients taking a statin showed significantly larger mean value of changes in PT-INR vs. those not taking a statin (0.34±0.54 vs. 0.06±0.36,P=0.03). An increase in TTR (P<0.0001) was seen as well as a decrease in the frequency to modify the warfarin dose after ezetimibe treatment (P=0.02).
The study authors concluded a possible drug interaction between warfarin and ezetimibe may exist. However, because they did not measure NPC1L1 expression and vitamin K concentration, it is “uncertain whether an increase and stabilization in anticoagulant effect of warfarin with the ezetimibe additional treatment depend on NPC1L1 activity.”
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