Abstract 17086: Alirocumab LDL-C-Lowering Efficacy in Patients With Moderate CKD
Background: Patients with chronic kidney disease (CKD) are at increased risk of premature cardiovascular disease. Many of these patients require adjuvant lipid-lowering therapy because of dosing restrictions of some statins in patients with CKD.
Objective: To determine LDL-C lowering efficacy and safety of the PCSK9 inhibitor alirocumab (ALI) in patients with hypercholesterolemia and with or without moderate CKD.
Methods: This analysis included data from 10 ODYSSEY Phase 3 trials. Moderate CKD was defined as glomerular filtration rate 30-59 mL/min/1.73m2. LONG TERM and HIGH FH (n=2448) compared ALI 150 mg every two wks (Q2W) vs placebo. The remaining 6 trials (n=2535) evaluated ALI 75 mg Q2W vs placebo/ezetimibe, with increase to ALI 150 mg Q2W at wk 12 if LDL-C was ≥70 or ≥100 mg/dL at wk 8 depending on CV risk. Patients received stable background statin ± other LLT, except in ALTERNATIVE and MONO (no statin) and COMBO II (statin but no other LLT).
Results: Moderate CKD at baseline was present in 481/4983 (9.7%) of patients. Mean baseline LDL-C levels of patients with and without moderate CKD were 109.6 and 127.8 mg/dL, respectively, and 96.9% and 92.7% were receiving a statin. Overall, having moderate CKD did not impact the LDL-C lowering efficacy of ALI (Figure). The smaller LDL-C reduction (vs other studies) seen in alirocumab-treated patients with moderate CKD in the ALTERNATIVE study may be related to low patient number. Adverse events (AEs) were reported by 79.0% ALI vs 81.1% control patients with moderate CKD and 74.7% ALI vs 74.5% control patients without. AEs led to discontinuation in 10.0% ALI vs 8.2% control patients with moderate CKD and 6.0% ALI and 6.6% control patients without.
Conclusions: ALI consistently lowered LDL-C levels vs control regardless of baseline moderate CKD status. There was no significant difference in % AEs between patients with and without moderate CKD and a numerically higher rate of discontinuations due to AEs in patients with moderate CKD.
Author Disclosures: P.P. Toth: Speakers Bureau; Modest; Genzyme. Speakers Bureau; Significant; Amarin, AstraZeneca, GSK, Kowa, Merck and Co.. Consultant/Advisory Board; Modest; Amgen, AstraZeneca, Merck and Co, Novartis, Sanofi, Regeneron. Consultant/Advisory Board; Significant; Kowa. C.P. Cannon: Research Grant; Modest; Accumetrics. Research Grant; Significant; Arisaph, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Janssen, Merck, Takeda. Consultant/Advisory Board; Modest; CSL Behring, Essentialis, GlaxoSmithKline, Merck, Kowa, Takeda, BMS, Pfizer. Consultant/Advisory Board; Significant; Sanofi, Regeneron Pharmaceuticals, Lipimedix. J.J. Kastelein: Honoraria; Modest; Dezima Pharmaceuticals, Regeneron, Sanofi, Eli Lilly, Pfizer, Amgen, Aegerion, Esperion. Honoraria; Significant; Isis, Cymabay, Gemphire. Consultant/Advisory Board; Modest; Dezima Pharmaceuticals, Regeneron, Sanofi, Eli Lilly, Pfizer, Amgen, Aegerion, Esperion. Consultant/Advisory Board; Significant; Isis, Cymabay, Gemphire. H.M. Colhoun: Research Grant; Modest; Pfizer, Roche, AstraZeneca, Boehringer-Ingelheim, Sanofi, Eli Lilly. Speakers Bureau; Significant; Sanofi, Regeneron. Honoraria; Significant; Sanofi, Regeneron. Ownership Interest; Modest; Roche. Consultant/Advisory Board; Significant; Regeneron, Sanofi. Other; Modest; Novartis, Merck. A. Koren: Employment; Significant; Sanofi. M.J. Louie: Employment; Significant; Regeneron Pharmaceuticals, Inc. G. Asset: Employment; Significant; Sanofi. D.J. Rader: Consultant/Advisory Board; Modest; Sanofi.
- © 2015 by American Heart Association, Inc.