Abstract 1609: Ezetimibe Added to Statin Therapy Markedly Improved in vivo Catabolism of ApoB-containing Lipoproteins: A Stable Isotope Study
Numerous intervention trials have established that magnitude of LDL-C reduction positively correlated with relative risk reduction of cardiovascular morbidity and mortality. Ezetimibe, a selective inhibitor of Niemann-Pick C1 Like 1, exerts a synergistic LDL-C lowering effect when combined with statin. However, the exact metabolic information about the combination therapy has not been well understood. We therefore performed stable isotope kinetic studies using deuterated leucine in 6 male hypercholestsrolemic patients at baseline, 6 weeks treatment with pravastatin 10mg (P), and further 6 weeks treatment with pravastatin 10mg and ezetimibe 10mg (P/E). Tracer/tracee ratio of apoB was determined by gas-chromatography mass spectrometry and modeling program (SAAMII) was used to estimate the fractional catabolic rate (FCR) of apoB. VLDL1 and VLDL2 apoB FCR were modestly increased by P (17% and 19%), which were further increased by P/E (8% and 27% vs P). P decreased IDL apoB by 45% primarily due to 33% increase in IDL apoB FCR and P/E yielded 79% increase in IDL apoB FCR, resulting in 51% reduction of IDL apoB. LDL apoB was decreased by 13% with P, then by 34% with P/E which primarily due to the increase in FCR (19% with P and 72% with P/E) without any changes in production rates. In summary, add-on therapy of ezetimibe on standard statin provided marked improvement on apoB catabolism among entire apoB-containing lipoproteins which resulted in substantial reduction of VLDL2, IDL, and LDL apoB concentrations. Combination therapy of ezetimibe with statin thus provides long term benefit by effectively decreasing atherogenic lipoproteins including remnant and LDL.