Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study

作者：Erik S.G. Stroes, John R. Guyton, Norman E. Lepor, Fernando Civeira, Daniel Gaudet, Gerald F. Watts, Marie T. Baccara‐Dinet, Guillaume Lecorps, Garen Z. Manvelian, Michel Farnier, Karam Kostner, Sam J. Lehman, Olivier S Descamps, Lien Gheyle, Chantal Mathieu, Jean Bergeron, Tom Elliott, Gabriel Girard, Arpeta Gupta, Gordon N. Hoag, Jens Dahlgaard Hove, Jørgen Jeppesen, J.H. Kjærulf, KIM KLARLUND, K.K. Thomsen, Dick C.G. Basart, Adriaan Kooy, Anho H Liem, H. Swart, Roland P.T. Troquay, J Van Het Hof‐Wiersma, P. P. Viergever, Frank L.J. Visseren, Robert Neil Doughty, Robert C. Scott, Carlos Calvo, José Luis Díaz-Díaz, Francisco Fuentes, Blas Gil Extremera, Carlos Rilova Jericó, Laia Matas Pericas, Juan Díaz García, D. Eric Bolster, Michael J. Koren, Mahfouz El Shahawy, Gil M. Vardi, Debra L. Weinstein, K. Zuzarte, Henry N. Ginsberg, Jennifer G. Robinson, Daniel James Rader, Christopher Paul Cannon, Helen Martina Colhoun, John J.P. Kastelein, Yong Huo, ANDERS G. OLSSON, David D. Waters, Dominique G. Larrey, Robert S. Rosenson, PETER A. PATRIARCA, Geert Molenberghs, Pierluigi Tricoci, Kenneth W. Mahaffey, Renato D. Lópes, Bimal R. Shah, Rajendra H. Mehta, Matthew T. Roe, Zubin J. Eapen, Luciana Vidal Armaganijan, Adriana Bertolami, Sergio Leonardi, Brad J. Kolls, J. Dedrick Jordan, Grégory Ducrocq, Étienne Puymirat, Robin Mathews · 发表于：Journal of the American Heart Association · 年份：2016 · DOI：10.1161/jaha.116.003421 · 被引用次数：102 · 研究领域：Lipoproteins and Cardiovascular Health、Diabetes, Cardiovascular Risks, and Lipoproteins、Rheumatoid Arthritis Research and Therapies

BACKGROUND: The PCSK9 antibody alirocumab (75 mg every 2 weeks; Q2W) as monotherapy reduced low-density lipoprotein-cholesterol (LDL-C) levels by 47%. Because the option of a monthly dosing regimen is convenient, ODYSSEY CHOICE II evaluated alirocumab 150 mg Q4W in patients with inadequately controlled hypercholesterolemia and not on statin (majority with statin-associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone. METHODS AND RESULTS: Patients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment to 150 mg Q2W at week (W) 12 if W8 predefined LDL-C target levels were not met. The primary efficacy endpoint was LDL-C percentage change from baseline to W24. Mean baseline LDL-C levels were 163.9 mg/dL (alirocumab 150 mg Q4W, n=59), 154.5 mg/dL (alirocumab 75 mg Q2W, n=116), and 158.5 mg/dL (placebo, n=58). In the alirocumab 150 mg Q4W and 75 mg Q2W groups (49.1% and 36.0% of patients received dose adjustment, respectively), least-squares mean LDL-C changes from baseline to W24 were -51.7% and -53.5%, respectively (placebo [+4.7%]; both groups P<0.0001 versus placebo). In total, 63.9% and 70.3% of alirocumab-treated patients achieved their LDL-C targets at W24. Treatment-emergent adverse events occurred in 77.6% (alirocumab 150 mg Q4W), 73.0% (alirocumab 75 mg Q2W), and 63.8% (placebo) of patients, with injection-site reactions among the most common treatment-emergent adverse events. CONC...