OBJECTIVES: The aim of this study was to compare biweekly and monthly evolocumab with placebo and oral ezetimibe in patients with hypercholesterolemia in a phase III trial. BACKGROUND:Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced LDL-C in phase II trials. METHODS: Patients 18 to 80 years of age with fasting low-density lipoprotein cholesterol (LDL-C) ≥100 and <190 mg/dl and Framingham risk scores ≤10% were randomized (1:1:1:1:2:2) to oral placebo and subcutaneous (SC) placebo biweekly; oral placebo and SC placebo monthly; ezetimibe and SC placebo biweekly; ezetimibe and SC placebo monthly; oral placebo and evolocumab 140 mg biweekly; or oral placebo and evolocumab 420 mg monthly. RESULTS: A total of 614 patients were randomized and administered doses. Evolocumab treatment reduced LDL-C from baseline, on average, by 55% to 57% more than placebo and 38% to 40% more than ezetimibe (p < 0.001 for all comparisons). Evolocumab treatment also favorably altered other lipoprotein levels. Treatment-emergent adverse events (AEs), muscle-related AEs, and laboratory abnormalities were comparable across treatment groups. CONCLUSIONS: In the largest monotherapy trial using a PCSK9 inhibitor to date, evolocumab yielded significant LDL-C reductions compared with placebo or ezetimibe and was well tolerated in patients with hypercholesterolemia. (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 [MENDEL-2]; NCT01763827).
RCT Entities:
OBJECTIVES: The aim of this study was to compare biweekly and monthly evolocumab with placebo and oral ezetimibe in patients with hypercholesterolemia in a phase III trial. BACKGROUND:Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced LDL-C in phase II trials. METHODS:Patients 18 to 80 years of age with fasting low-density lipoprotein cholesterol (LDL-C) ≥100 and <190 mg/dl and Framingham risk scores ≤10% were randomized (1:1:1:1:2:2) to oral placebo and subcutaneous (SC) placebo biweekly; oral placebo and SC placebo monthly; ezetimibe and SC placebo biweekly; ezetimibe and SC placebo monthly; oral placebo and evolocumab 140 mg biweekly; or oral placebo and evolocumab 420 mg monthly. RESULTS: A total of 614 patients were randomized and administered doses. Evolocumab treatment reduced LDL-C from baseline, on average, by 55% to 57% more than placebo and 38% to 40% more than ezetimibe (p < 0.001 for all comparisons). Evolocumab treatment also favorably altered other lipoprotein levels. Treatment-emergent adverse events (AEs), muscle-related AEs, and laboratory abnormalities were comparable across treatment groups. CONCLUSIONS: In the largest monotherapy trial using a PCSK9 inhibitor to date, evolocumab yielded significant LDL-C reductions compared with placebo or ezetimibe and was well tolerated in patients with hypercholesterolemia. (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 [MENDEL-2]; NCT01763827).
Authors: Lotte C A Stiekema; Erik S G Stroes; Simone L Verweij; Helina Kassahun; Lisa Chen; Scott M Wasserman; Marc S Sabatine; Venkatesh Mani; Zahi A Fayad Journal: Eur Heart J Date: 2019-09-01 Impact factor: 29.983
Authors: Frederick J Raal; Robert P Giugliano; Marc S Sabatine; Michael J Koren; Dirk Blom; Nabil G Seidah; Narimon Honarpour; Armando Lira; Allen Xue; Padmaja Chiruvolu; Simon Jackson; Mei Di; Matthew Peach; Ransi Somaratne; Scott M Wasserman; Rob Scott; Evan A Stein Journal: J Lipid Res Date: 2016-04-21 Impact factor: 5.922
Authors: Alessandro Squizzato; Matteo Basilio Suter; Marta Nerone; Robert Patrick Giugliano; Francesco Dentali; Andrea Maria Maresca; Leonardo Campiotti; Anna Maria Grandi; Luigina Guasti Journal: Intern Emerg Med Date: 2017-07-10 Impact factor: 3.397