Efficacy and safety of alirocumab in statin-intolerant patients over 3 years: open-label treatment period of the ODYSSEY ALTERNATIVE trial.

Journal Article (Journal Article)

BACKGROUND: The 24-week randomized, double-blind ODYSSEY ALTERNATIVE trial (NCT01709513) demonstrated significant low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 inhibitor alirocumab vs ezetimibe in statin-intolerant patients, with significantly fewer skeletal muscle events (SMEs; 32.5%) vs atorvastatin (46.0%; hazard ratio: 0.61, 95% confidence interval: 0.38 to 0.99, P = .042). OBJECTIVE: ALTERNATIVE participants could enter an open-label treatment period (OLTP) for assessment of long-term safety. METHODS: Two hundred and eighty one patients entered the OLTP; 93.7%, 84.0%, and 92.9% of patients who received atorvastatin, ezetimibe, and alirocumab, respectively, during double-blind treatment, including 216 patients (76.9%) who completed double-blind treatment, as well as patients who either prematurely discontinued treatment due to SME (n = 51 [18.1%]) or other reasons (n = 14 [5.0%]) but completed week 24 assessments. All patients in the OLTP received alirocumab (75 or 150 mg every 2 weeks based on investigator decision) for ∼3 years or until commercial availability, whichever came first. RESULTS: SMEs were reported by 38.4% of patients in the OLTP. Safety results from the OLTP were similar to those of the alirocumab group in the double-blind period, except for a lower rate of discontinuations due to SMEs observed with alirocumab in the OLTP (3.2% vs 15.9% in the double-blind period). At OLTP week 8, mean LDL-C reduction from baseline (=week 0 of double-blind period) was 52.0%, with reductions sustained through to the end-of-treatment visits (55.4% and 53.7% reduction at weeks 100 and 148, respectively). CONCLUSIONS: In this population of statin-intolerant patients, alirocumab was well tolerated and produced durable LDL-C reductions over 3 years.

Full Text

Duke Authors

Cited Authors

  • Moriarty, PM; Thompson, PD; Cannon, CP; Guyton, JR; Bergeron, J; Zieve, FJ; Bruckert, E; Jacobson, TA; Baccara-Dinet, MT; Zhao, J; Donahue, S; Ali, S; Manvelian, G; Pordy, R

Published Date

  • 2020

Published In

Volume / Issue

  • 14 / 1

Start / End Page

  • 88 - 97.e2

PubMed ID

  • 32192644

International Standard Serial Number (ISSN)

  • 1933-2874

Digital Object Identifier (DOI)

  • 10.1016/j.jacl.2020.01.001


  • eng

Conference Location

  • United States