Association between Serum Oxysterols and Coronary Plaque Regression during Lipid-Lowering Therapy with Statin and Ezetimibe: Insights from the CuVIC Trial

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  • Nakano Yasuhiro
    Department of Cardiovascular Medicine, Kyushu University Hospital
  • Yamamoto Mitsutaka
    Department of Cardiovascular Medicine, Harasanshin Hospital
  • Matoba Tetsuya
    Department of Cardiovascular Medicine, Kyushu University Hospital
  • Katsuki Shunsuke
    Department of Cardiovascular Medicine, Kyushu University Hospital
  • Nakashiro Soichi
    Department of Cardiovascular Medicine, Matsuyama Red Cross Hospital
  • Takase Susumu
    Department of Cardiovascular Medicine, Kyushu University Hospital
  • Akiyama Yusuke
    Department of Cardiovascular Medicine, Kyushu University Hospital
  • Nagata Takuya
    Department of Cardiovascular Medicine, Kyushu University Hospital
  • Mukai Yasushi
    Department of Cardiovascular Medicine, Japanese Red Cross Fukuoka Hospital
  • Inoue Shujiro
    Department of Cardiovascular Medicine, Aso Iizuka Hospital
  • Oi Keiji
    Department of Cardiovascular Medicine, Saiseikai Fukuoka General Hospital
  • Higo Taiki
    Department of Cardiovascular Medicine, National Hospital Organization Kyushu Medical Centre
  • Takemoto Masao
    Cardiovascular Center, Steel Memorial Yawata Hospital
  • Suematsu Nobuhiro
    Department of Cardiovascular Medicine, Saiseikai Fukuoka General Hospital
  • Eshima Kenichi
    Department of Cardiovascular Medicine, Saga-ken Medical Centre Koseikan
  • Miyata Kenji
    Department of Cardiovascular Medicine, Japan Community Health Care Organization, Kyushu Hospital
  • Usui Makoto
    Department of Cardiovascular Medicine, Hamanomachi Hospital
  • Sadamatsu Kenji
    Department of Cardiovascular Medicine, Omuta City Hospital
  • Kadokami Toshiaki
    Department of Cardiovascular Medicine, Saiseikai Futsukaichi Hospital
  • Hironaga Kiyoshi
    Department of Cardiovascular Medicine, Fukuoka City Hospital
  • Ichi Ikuyo
    Graduate School of Humanities and Science, Ochanomizu University
  • Todaka Koji
    Center for Clinical and Translational Research of Kyushu University Hospital
  • Kishimoto Junji
    Center for Clinical and Translational Research of Kyushu University Hospital
  • Tsutsui Hiroyuki
    Department of Cardiovascular Medicine, Kyushu University Hospital Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences

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  • Oxysterol: Residual Lipid Risk for Interventional Cardiology

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<p> Aim: Several clinical trials using intravascular ultrasound (IVUS) evaluation have demonstrated that intensive lipid-lowering therapy by statin or a combination therapy with statin and ezetimibe results in significant regression of coronary plaque volume. However, it remains unclear whether adding ezetimibe to statin therapy affects coronary plaque composition and the molecular mechanisms of plaque regression. We conducted this prospective IVUS analysis in a subgroup from the CuVIC trial.</p><p>Methods: The CuVIC trial was a prospective randomized, open, blinded-endpoint trial conducted among 11 cardiovascular centers, where 260 patients with coronary artery disease who received coronary stenting were randomly allocated into either the statin group (S) or the combined statin and ezetimibe group (S＋E). We enrolled 79 patients (S group, 39 patients; S＋E group, 40 patients) in this substudy, for whom serial IVUS images of nonculprit lesion were available at both baseline and after 6–8 months of follow-up.</p><p>Results: After the treatment period, the S＋E group had significantly lower level of low-density lipoprotein cholesterol (LDL-C; 80.9±3.7 vs. 67.7±3.8 mg/dL, p=0.0143). Campesterol, a marker of cholesterol absorption, and oxysterols (β-epoxycholesterol, 4β-hydroxycholesterol, and 27-hydroxycholesterol) were also lower in the S＋E group. IVUS analyses revealed greater plaque regression in the S＋E group than in the S group (−6.14% vs. −1.18% for each group, p=0.042). It was noteworthy that the lowering of campesterol and 27-hydroxycholesterol, but not LDL-C, had a significant positive correlation with plaque regression.</p><p>Conclusions: Compared with statin monotherapy, ezetimibe in combination with statin achieved significantly lower LDL-C, campesterol, and 27-hydroxycholesterol, which resulted in greater coronary plaque regression.</p>

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