Tamio Teramoto1, Makiko Usami2, Yoshiharu Takagi3, Marie T Baccara-Dinet4. 1. Teikyo Academic Research Center, Teikyo University. 2. Cardiovascular Medical, Sanofi. 3. Clinical Sciences and Operations, Sanofi. 4. PCSK9 Development and Launch Unit, Sanofi.
Abstract
AIM: To examine the efficacy and safety of alirocumab in Japanese patients with dyslipidemia with or without diabetes mellitus (DM). METHODS: Patients (n=216) with heterozygous familial hypercholesterolemia (heFH), non-FH at high cardiovascular risk with coronary artery disease (CAD), or category III (primary prevention) were enrolled; 148 (68.5%) patients had a diagnosis of DM at baseline. Patients were randomized (2:1), with stratification factor (heFH, non-FH), to alirocumab (75 mg every 2 weeks [Q2W] with increase to 150 mg if week 8 LDL-C was above predefined limits) or placebo subcutaneously for 52 weeks on top of stable statin therapy. RESULTS: At Week 24, least square (LS) mean±standard error changes in low-density lipoprotein cholesterol (LDL-C) concentration from baseline in alirocumab-treated patients were －63.1±1.6% and －60.8±2.7% in those with and without DM. These LDL-C reductions were maintained to Week 52: －63.0±1.6% (LS mean difference vs placebo －62.4±3.0%; P＜0.0001) with DM and －61.3±2.8% (LS mean difference vs placebo －53.4±4.0%; P＜0.0001) without DM. The most common adverse events in the alirocumab group were nasopharyngitis, back pain, injection site reaction, and fall. No particular safety signals or concerns were noted between DM and non-DM groups at 52 weeks. A dose-increase in alirocumab from 75 to 150 mg Q2W was necessary in two heFH patients, neither of whom had DM. CONCLUSIONS: In high-cardiovascular-risk Japanese patients with hypercholesterolemia on stable statin therapy, alirocumab produced substantial and sustained LDL-C reductions throughout the 52-week study regardless of DM status at baseline, with a similar safety profile to placebo.
RCT Entities:
AIM: To examine the efficacy and safety of alirocumab in Japanese patients with dyslipidemia with or without diabetes mellitus (DM). METHODS:Patients (n=216) with heterozygous familial hypercholesterolemia (heFH), non-FH at high cardiovascular risk with coronary artery disease (CAD), or category III (primary prevention) were enrolled; 148 (68.5%) patients had a diagnosis of DM at baseline. Patients were randomized (2:1), with stratification factor (heFH, non-FH), to alirocumab (75 mg every 2 weeks [Q2W] with increase to 150 mg if week 8 LDL-C was above predefined limits) or placebo subcutaneously for 52 weeks on top of stable statin therapy. RESULTS: At Week 24, least square (LS) mean±standard error changes in low-density lipoprotein cholesterol (LDL-C) concentration from baseline in alirocumab-treated patients were －63.1±1.6% and －60.8±2.7% in those with and without DM. These LDL-C reductions were maintained to Week 52: －63.0±1.6% (LS mean difference vs placebo －62.4±3.0%; P＜0.0001) with DM and －61.3±2.8% (LS mean difference vs placebo －53.4±4.0%; P＜0.0001) without DM. The most common adverse events in the alirocumab group were nasopharyngitis, back pain, injection site reaction, and fall. No particular safety signals or concerns were noted between DM and non-DM groups at 52 weeks. A dose-increase in alirocumab from 75 to 150 mg Q2W was necessary in two heFHpatients, neither of whom had DM. CONCLUSIONS: In high-cardiovascular-risk Japanese patients with hypercholesterolemia on stable statin therapy, alirocumab produced substantial and sustained LDL-C reductions throughout the 52-week study regardless of DM status at baseline, with a similar safety profile to placebo.