Professor Colhoun has received research grants from Roche, Pfizer, Eli Lilly, Boehringer Ingelheim, and AstraZeneca; speakers bureau fees from Pfizer; honoraria from Pfizer; has ownership interest in Roche; and has received consultant/advisory board fees from Pfizer, Sanofi Aventis, Regeneron Pharmaceuticals, Inc

Professor Colhoun has received research grants from Roche, Pfizer, Eli Lilly, Boehringer Ingelheim, and AstraZeneca; speakers bureau fees from Pfizer; honoraria from Pfizer; has ownership interest in Roche; and has received consultant/advisory board fees from Pfizer, Sanofi Aventis, Regeneron Pharmaceuticals, Inc., Novartis, and Eli Lilly. and European lipid management guidelines support non\HDL\C and apoB as targets for lipid\lowering therapy. Methods and Results This analysis evaluated the efficacy of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, on non\HDL\C and apoB. Data were derived from 4983 patients enrolled in 10 randomized, placebo\ or ezetimibe\controlled Phase 3 ODYSSEY trials. Primary end point for this pooled analysis was percent reduction in non\HDL\C and apoB at Week 24; secondary end points included the percentage of patients achieving guideline\directed treatment goals (National Lipid Association guidelines: non\HDL\C 100 or 130?mg/dL for patients at very high and high cardiovascular risk, respectively; European Society of Cardiology/European Atherosclerosis Society guidelines: apoB 80?mg/dL for patients at very\high cardiovascular risk). Data were grouped according to comparator, Polydatin (Piceid) alirocumab starting dose, and concomitant statin use. Compared with controls, alirocumab produced significantly greater reductions in non\HDL\C and apoB at Week 24 ( em P /em 0.0001), an effect extending up to 78?weeks. More alirocumab\treated patients achieved levels of non\HDL\C 100?mg/dL and apoB 80?mg/dL ( em P /em 0.0001 versus control). By Week 24, 70% of alirocumab\treated patients on background statin achieved non\HDL\C 100 or 130?mg/dL, and apoB 80?mg/dL. Safety was comparable across pooled groups and in line with previous reports. Conclusions Alirocumab produced significant, sustained reductions in non\HDL\C and apoB, allowing more patients to achieve lipid goals compared with placebo or ezetimibe and irrespective of maximally tolerated statin use. strong class=”kwd-title” Keywords: alirocumab, apolipoprotein B, cholesterol\lowering, hypercholesterolemia, non\high\density lipoprotein cholesterol, PCSK9 strong class=”kwd-title” Subject Categories: Clinical Studies, Lipids and Cholesterol, Cardiovascular Disease Clinical Perspective What Is New? Non\high\density lipoprotein cholesterol (non\HDL\C) and apolipoprotein B (apoB) are specified as treatment targets by some international lipid guidelines. Alirocumab produced significant, sustained reductions in non\HDL\C and apoB, allowing more patients to achieve lipid goals. What Are the Clinical Implications? Non\HDL\C and apoB are better predictors of atherosclerotic cardiovascular disease risk than calculated low\density lipoprotein cholesterol alone. Alirocumab effectively reduces non\HDL\C and apoB levels, allowing for better achievement of non\HDL\C and apoB levels corresponding to guideline treatment goals. Introduction Guidelines for the management of dyslipidemia have traditionally recommended reductions in the level of low\density lipoprotein cholesterol (LDL\C) as the primary lipid target of therapy to reduce the risk of atherosclerotic cardiovascular disease (ASCVD). However, LDL\C has limitations as a predictor of ASCVD risk, particularly in patients with elevated triglyceride levels.1 Additional pro\atherogenic lipid parameters, such as non\high\density lipoprotein Polydatin (Piceid) cholesterol (non\HDL\C) and KIAA0243 apolipoprotein (apo) B, may provide important diagnostic information to guide the assessment and management of dyslipidemia and ASCVD risk.2 Current US National Lipid Association recommendations and European Society of Cardiology/European Atherosclerosis Society guidelines have?recognized the importance of these lipid parameters. The National Lipid Association recommends non\HDL\C as a co\primary therapy target?alongside LDL\C, and apoB as a secondary target, whereas European guidelines recommend both non\HDL\C and apoB as secondary targets.3, 4 Although the 2013 American College of Cardiology/American Heart Association guidelines Polydatin (Piceid) do not specify non\HDL\C treatment thresholds,5 recent recommendations from the 2016 American College of Cardiology Consensus Decision Pathway on the role of nonstatin therapies for LDL\C\lowering have introduced non\HDL\C thresholds in certain high\risk patient groups.6 Alirocumab is a monoclonal proprotein convertase subtilisin/kexin type 9 inhibitor that helps prevent Polydatin (Piceid) LDL receptor degradation, thus increasing clearance of LDL\C and decreasing LDL\C blood levels. Alirocumab was evaluated in the ODYSSEY global Phase 3 clinical trial program comprising a comprehensive set of clinical studies in various patient populations. Individual studies7, 8, 9, 10, 11, 12, 13, 14 and a pooled analysis of 8 studies in patients receiving background statin therapy15 have shown that alirocumab produces significant reductions in LDL\C compared with placebo or ezetimibe in patients at Polydatin (Piceid) high cardiovascular risk. The data for this analysis included 10 completed ODYSSEY studies in a broad range of patients with hypercholesterolemia: 8 studies including alirocumab administered to patients treated with background statin, the majority of whom received maximally tolerated statin, or other lipid\lowering therapies, and 2 studies involving alirocumab administered to patients without background statin. The main aim of the analysis was to investigate the effect of alirocumab on levels of non\HDL\C and apoB. Methods Study Designs and Participants In this analysis, data were pooled from 10 Phase 3 trials in the ODYSSEY program, involving.