Michel Farnier1, Daniel Gaudet2, Velichka Valcheva3, Pascal Minini4, Kathryn Miller5, Bertrand Cariou6. 1. Lipid Clinic, Point Médical, Dijon, France. Electronic address: michelfarnier@nerim.net. 2. Lipidology Unit, Community Genomic Medicine Center, Department of Medicine, Université de Montréal and ECOGENE-21 Clinical and Translational Research Center, Chicoutimi, Quebec, Canada. 3. Global Medical Affairs, Sanofi, Paris, France. 4. Biostatistics and Programming, Sanofi, Chilly-Mazarin, France. 5. Biostatistics and Data Management, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. 6. Department of Endocrinology, l'Institut du Thorax, Nantes University Hospital, Nantes, France.
Abstract
OBJECTIVES: Despite maximally tolerated statin therapy, many patients with high cardiovascular risk, with or without heterozygous familial hypercholesterolemia may require additional low-density lipoprotein cholesterol (LDL-C) reduction. We report pooled alirocumab (ALI) efficacy and safety data from eight Phase 3 trials in 4629 hypercholesterolemia patients, receiving background statin therapy. MATERIAL AND METHODS: Studies were pooled by ALI dose and control: ALI 75/150mg every 2weeks (Q2W; dose increased to 150mg Q2W at Week 12 based on Week 8 LDL-C) versus ezetimibe (EZE; Pool 1) or placebo (PBO; Pool 2), and ALI 150mg Q2W versus PBO (Pool 3). RESULTS:Mean baseline LDL-C was 109 vs. 105mg/dL (Pool 1), 129 vs. 130mg/dL (Pool 2) and 126 vs. 125mg/dL (Pool 3). ALI 75/150mg Q2W reduced LDL-C by 48.9% (vs. -19.3% EZE) and 48.6% (vs. +4.2% PBO) from baseline to Week 24, and ALI 150mg Q2W reduced LDL-C by 60.4% (vs. +0.5% PBO; all p<0.0001). LDL-C reductions were sustained to Week 104. Risk-based LDL-C goals (<70mg/dL or <100mg/dL) were achieved by 78.0%, 75.2%, and 79.0% (Pool 1-3) of ALI-treated patients (vs. 52.4%, 6.4%, and 8.4%, respectively, for controls) at Week 24. Consistent reductions were observed in apolipoprotein B, non-high-density lipoprotein cholesterol, and lipoprotein (a) (p<0.0001 vs. control). Common adverse events in ALI-treated patients were nasopharyngitis, injection-site reactions, upper respiratory tract infections, and influenza. CONCLUSIONS:Alirocumab treatment significantly reduced LDL-C in high cardiovascular risk patients, enabling most to achieve risk-based LDL-C goals.
RCT Entities:
OBJECTIVES: Despite maximally tolerated statin therapy, many patients with high cardiovascular risk, with or without heterozygous familial hypercholesterolemia may require additional low-density lipoprotein cholesterol (LDL-C) reduction. We report pooled alirocumab (ALI) efficacy and safety data from eight Phase 3 trials in 4629 hypercholesterolemiapatients, receiving background statin therapy. MATERIAL AND METHODS: Studies were pooled by ALI dose and control: ALI 75/150mg every 2weeks (Q2W; dose increased to 150mg Q2W at Week 12 based on Week 8 LDL-C) versus ezetimibe (EZE; Pool 1) or placebo (PBO; Pool 2), and ALI 150mg Q2W versus PBO (Pool 3). RESULTS: Mean baseline LDL-C was 109 vs. 105mg/dL (Pool 1), 129 vs. 130mg/dL (Pool 2) and 126 vs. 125mg/dL (Pool 3). ALI 75/150mg Q2W reduced LDL-C by 48.9% (vs. -19.3% EZE) and 48.6% (vs. +4.2% PBO) from baseline to Week 24, and ALI 150mg Q2W reduced LDL-C by 60.4% (vs. +0.5% PBO; all p<0.0001). LDL-C reductions were sustained to Week 104. Risk-based LDL-C goals (<70mg/dL or <100mg/dL) were achieved by 78.0%, 75.2%, and 79.0% (Pool 1-3) of ALI-treated patients (vs. 52.4%, 6.4%, and 8.4%, respectively, for controls) at Week 24. Consistent reductions were observed in apolipoprotein B, non-high-density lipoprotein cholesterol, and lipoprotein (a) (p<0.0001 vs. control). Common adverse events in ALI-treated patients were nasopharyngitis, injection-site reactions, upper respiratory tract infections, and influenza. CONCLUSIONS:Alirocumab treatment significantly reduced LDL-C in high cardiovascular risk patients, enabling most to achieve risk-based LDL-C goals.
Authors: Pragyi Shrestha; Saritha Adepu; Romain R Vivès; Rana El Masri; Astrid Klooster; Fleur Kaptein; Wendy Dam; Stephan J L Bakker; Harry van Goor; Bart van de Sluis; Jacob van den Born Journal: J Am Soc Nephrol Date: 2021-03-23 Impact factor: 14.978
Authors: Lawrence A Leiter; Bertrand Cariou; Dirk Müller-Wieland; Helen M Colhoun; Stefano Del Prato; Francisco J Tinahones; Kausik K Ray; Maja Bujas-Bobanovic; Catherine Domenger; Jonas Mandel; Rita Samuel; Robert R Henry Journal: Diabetes Obes Metab Date: 2017-10-10 Impact factor: 6.577