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Review
. 2024 Jul 16;10(4):342-352.
doi: 10.1093/ehjcvp/pvae025.

Safety of the PCSK9 inhibitor alirocumab: insights from 47 296 patient-years of observation

Shaun G Goodman  1   2 , Philippe Gabriel Steg  3 , Michael Szarek  4   5 , Deepak L Bhatt  6 , Vera A Bittner  7 , Rafael Diaz  8 , Robert A Harrington  9 , J Wouter Jukema  10   11 , Harvey D White  12 , Andreas M Zeiher  13 , Garen Manvelian  14 , Robert Pordy  14 , Yann Poulouin  15 , Wanda Stipek  14 , Genevieve Garon  16 , Gregory G Schwartz  17 ; ODYSSEY OUTCOMES Investigators
Collaborators, Affiliations
Review

Safety of the PCSK9 inhibitor alirocumab: insights from 47 296 patient-years of observation

Shaun G Goodman et al. Eur Heart J Cardiovasc Pharmacother. .

Abstract

The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

Keywords: Alirocumab; Cholesterol; PCSK9; Safety.

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Figures

Graphical Abstract
Graphical Abstract
Overview of the clinical efficacy and safety of alirocumab as observed in the ODYSSEY OUTCOMES clinical trial. MACE, major adverse cardiovascular event.
Figure 1
Figure 1
Frequency of laboratory abnormalities and adverse events in the (A) overall patient population and (B) subgroup of 8228 patients (43.5%) eligible for 3−5 years of treatment (modified with permission) in the ODYSSEY OUTCOMES trial., ALN, alanine transaminase; AST, aspartate aminotransferase; CK, creatine kinase; ULN, upper limit of normal.
Figure 2
Figure 2
Kaplan–Meier cumulative incidence for time to first local injection site reaction in the subgroup of 8228 patients (43.5%) eligible for 3−5 years of treatment over ∼4 years. CI, confidence interval; HR, hazard ratio. (Reproduced with permission).
Figure 3
Figure 3
Risk of any fatal or non-fatal stroke, ischaemic stroke, and haemorrhagic stroke in the ODYSSEY OUTCOMES trial.,
See this image and copyright information in PMC

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