Long-term efficacy and safety data of PCSK9 antibody in post-ACS patients

Long-Term Efficacy, Safety, and Tolerability of Alirocumab in 8242 Patients Eligible for 3 to 5 Years of Placebo-Controlled Observation in the ODYSSEY OUTCOMES Trial

Literature - Goodman SG, Steg PS, Poulouin Y, et al - J Am Heart Assoc. 2023 Sep 19;12(18):e029216. doi: 10.1161/JAHA.122.029216

Introduction and methods

Background and aim of the study

In the ODYSSEY OUTCOMES trial, the PCSK9 antibody alirocumab significantly lowered LDL-c levels, and the risk of MACE and death in patients with recent ACS over a median follow-up of 2.8 years [1-2]. The aim of this post-hoc analysis of the ODYSSEY OUTCOMES trial was to assess the long-term efficacy, safety and tolerability of alirocumab compared with placebo in patients eligible for 3 to 5 years of follow-up.


The ODYSSEY OUTCOMES trial was a double-blind, placebo-controlled trial in which 18,924 patients with recent ACS (1–12 months prior) and elevated levels of atherogenic lipoproteins despite high-intensity or maximum-tolerated statin therapy were randomized to alirocumab (75 mg subcutaneously every 2 weeks) or placebo. 8242 patients were eligible for 3 to 5 years of follow-up (n=4116 in the alirocumab group, and n=4126 in the placebo group; median follow-up of 3.3 years; 24.610 patient-years of observation), 6651 patients were eligible for 3 to 4 years of follow-up, and 1574 patients were eligible for 4 to 5 years of follow-up.

Main results

Efficacy outcomes

  • Over a 4-year period, the incidence rate of cardiovascular death was 3.9% in the alirocumab group vs. 5.0% in the placebo group (HR: 0.81; 95%CI: 0.65-1.01; P=0.06; NNT=91).
  • Alirocumab also reduced the risk of MACE (consisting of CHD, nonfatal MI, fatal or nonfatal ischemic stroke, and unstable angina requiring hospitalization) compared with placebo over 4 years (HR: 0.83; 95%CI: 0.74-0.94; P=0.003; NNT=42).

Safety outcomes

  • 3217 (78.3%) patients in the alirocumab group experienced at least 1 adverse event compared with 3303 (80.25) patients in the placebo group. 27.5% of patients in the alirocumab group vs. 29.4% of patients in the placebo group experienced a serious adverse event.
  • Local injection site reactions occurred more frequently in the alirocumab group compared with the placebo group (HR: 1.71; 95%CI: 1.34-2.17). Nevertheless, the incidence of these reactions was lower than 5% over the 4-year period and mostly occurred within the first 6 months.
  • Other adverse events occurred with a similar frequency in both treatment groups, which included new-onset diabetes, worsening or complications of diabetes, neurocognitive events, elevations in ALT, AST, bilirubin, or creatine phosphokinase, and permanent discontinuation of study drug due to adverse event.


This post-hoc analysis of the ODYSSEY OUTCOMES trial showed that alirocumab reduces MACE in post-ACS patients who were treated maximum-tolerated statin therapy during the extended follow-up period (3 to 5 years). Treatment with alirocumab was safe, and well-tolerated, and only associated with a small increase in local injection-site reactions.


1. Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018 Nov 29;379(22):2097-2107.

2. Steg PG, Szarek M, Bhatt DL, et al. Effect of alirocumab on mortality after acute coronary syndromes. Circulation. 2019 Jul 9;140(2):103-112.

Find this article online at J Am Heart Assoc.

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