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Ezetimibe in Combination With Statins Ameliorates Endothelial Dysfunction in Coronary Arteries After Stenting: The
Susumu Takase1, Tetsuya Matoba2, Soichi Nakashiro1
1From the Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan (S.T., T.M., S.N., T.H., K. Egashira, K. Sunagawa); Department of Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan (S.T., T.M., S.N., Y.M., S.I., K.O., T.H., S.K., M.T., K. Sunagawa); Japanese Red Cross Fukuoka Hospital, Japan (N.S.); St. Mary's Hospital, Kurume, Japan (K. Eshima); Japan Community Health Care Organization, Kyushu Hospital, Fukuoka, Japan (K.M.); Harasanshin Hospital, Fukuoka, Japan (M.Y.); Hamanomachi Hospital, Fukuoka, Japan (M.U.); Saga-ken Medical Centre Koseikan, Saga, Japan (K. Sadamatsu); National Hospital Organization Kyushu Medical Centre, Fukuoka, Japan (S.S.); Saiseikai Futsukaichi Hospital, Chikushino, Japan (T.K.); Saiseikai Fukuoka General Hospital, Japan; Fukuoka City Hospital, Japan (K.H.); Graduate School of Humanities and Science, Ochanomizu University, Tokyo, Japan (I.I.); Center for Clinical and Translational Research, Kyushu University, Fukuoka, Japan (K.T., J.K.); and Department of Research and Development of Next Generation Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan (J.K.).
Objectives:
We sought to investigate whether treatment with ezetimibe in combination with statins improves coronary endothelial function in target vessels in coronary artery disease patients after coronary stenting.
Approach And Results:
We conducted a multicenter, prospective, randomized, open-label, blinded-end point trial among 11 cardiovascular treatment centers. From 2011 to 2013, 260 coronary artery disease patients who underwent coronary stenting were randomly allocated to 2 arms (statin monotherapy, S versus ezetimibe [10 mg/d]+statin combinational therapy, E+S). We defined target vessel dysfunction as the primary composite outcome, which comprised target vessel failure during treatment and at the 6- to 8-month follow-up coronary angiography and coronary endothelial dysfunction determined via intracoronary acetylcholine testing performed in cases without target vessel failure at the follow-up coronary angiography. Coadministration of ezetimibe with statins further lowered low-density lipoprotein cholesterol levels (83±23 mg/dL in S versus 67±23 mg/dL in E+S; P<0.0001), with significant decreases in oxidized low-density lipoprotein and oxysterol levels. Among patients without target vessel failure, 46 out of 89 patients (52%) in the S arm and 34 out of 96 patients (35%) in the E+S arm were found to have coronary endothelial dysfunction (P=0.0256), and the incidence of target vessel dysfunction at follow-up was significantly decreased in the E+S arm (69/112 (62%) in S versus 47/109 (43%) in E+S; P=0.0059). A post hoc analysis of post-treatment low-density lipoprotein cholesterol-matched subgroups revealed that the incidence of both target vessel dysfunction and coronary endothelial dysfunction significantly decreased in the E+S arm, with significant reductions in oxysterol levels.
Conclusions:
The CuVIC trial (Effect of Cholesterol Absorption Inhibitor Usage on Target Vessel Dysfunction after Coronary Stenting) has shown that ezetimibe with statins, compared with statin monotherapy, improves functional prognoses, ameliorating endothelial dysfunction in stented coronary arteries, and was associated with larger decreases in oxysterol levels.
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