Apolipoprotein A-I infusions and cardiovascular outcomes in acute myocardial infarction according to baseline LDL-cholesterol levels: the AEGIS-II trial
Authors: Gibson C Michael , Duffy Danielle , Bahit Maria Cecilia , Chi Gerald , White Harvey , Korjian Serge , Alexander John H , Lincoff A Michael , Heise Mark , Kingwell Bronwyn A , Nicolau Jose C , Lopes Renato D , Cornel Jan H , Lewis Basil S , Vinereanu Dragos , Goodman Shaun G , Bode Christoph , Steg Ph Gabriel , Libby Peter , Sacks Frank M , Bainey Kevin R , Ridker Paul M , Mahaffey Kenneth W , Aylward Philip , Nicholls Stephen J , Pocock Stuart J , Mehran Roxana , Harrington Robert A ,   for the AEGIS-II Committees and Investigators, Gibson C Michael , Alexander John H , Aylward Philip A , Bhatt Deepak L , Bode Christoph , Goodman Shaun G , Harrington Robert A , Mahaffey Kenneth W , Lincoff A Michael , Mehran Roxana , Nicholls Stephen J , Pocock Stuart J , Ridker Paul M , Steg P Gabriel , Tendera Michal , Duffy Danielle , Tricoci Pierluigi , Gibson C Michael , Alexander John H , Kastelein John J P , Lincoff A Michael , Mehran Roxana , Pocock Stuart J , Steg P Gabriel , Duffy Danielle , Gibson C Michael , Bahit Cecilia , Figtree Gemma , Huber Kurt , Vranckx Pascal , Lopes Renato D , Nicolau Jose Carlos , Gotcheva Nina , Bainey Kevin , Prieto Juan Carlos , Triana Miguel Urina , Solar Miroslav , Viigimaa Margus , Laine Mika , Montalescot Gilles , Shaburishvili Tamaz , Duerschmied Daniel , Tousoulis Dimitris , Lee Michael , Merkely Bela , Lewis Basil , Ambrosio Giuseppe , di Perugia Ospedale S , Yasuda Satoshi , Erglis Andrejs , Slapikas Rimvydas , Fong Alan , Pons Jose Luis Leiva , Cornel Jan H , White Harvey , Juliebø Vibeke , Horna Manuel , Trebacz Jaroslaw , Morais João , Vinereanu Dragos , Zenin Sergey , Tasic Nebojsa , Tan Jack , Murin Jan , Burgess Lesley , Kang Hyun Jae , Fillat Angel Cequier , Hagström Emil , Windecker Stephan , Lin Jiunn-Lee , Sritara Piyamitr , Guray Umit , Kunadian Vijay , Parkhomenko Alexandr , Bonaca Marc , Povsic Thomas J , Gershlick Anthony , Betriu Amadeu 
Published: September 2024

Abstract

Background and Aims
In the AEGIS-II trial (NCT03473223), CSL112, a human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity, did not significantly reduce the risk of the primary endpoint through 90 days vs. placebo after acute myocardial infarction (MI). Nevertheless, given the well-established relationship between higher low-density lipoprotein cholesterol (LDL-C) and plaque burden, as well as greater risk reductions seen with PCSK9 inhibitors in patients with baseline LDL-C ≥ 100 mg/dL on statin therapy, the efficacy of CSL112 may be influenced by baseline LDL-C.

Methods
Overall, 18 219 patients with acute MI, multivessel coronary artery disease, and additional risk factors were randomized to either four weekly infusions of 6 g CSL112 or placebo. This exploratory post-hoc analysis evaluated cardiovascular outcomes by baseline LDL-C in patients prescribed guideline-directed statin therapy at the time of randomization (n = 15 731).

Results
As baseline LDL-C increased, the risk of the primary endpoint at 90 days lowered in those treated with CSL112 compared with placebo. In patients with LDL-C ≥ 100 mg/dL at randomization, there was a significant risk reduction of cardiovascular death, MI, or stroke in the CSL112 vs. placebo group at 90, 180, and 365 days [hazard ratio .69 (.53–.90), .71 (.57–.88), and .78 (.65–.93)]. In contrast, there was no difference between treatment groups among those with LDL-C &lt; 100 mg/dL at baseline.

Conclusions
In this population, treatment with CSL112 compared to placebo was associated with a significantly lower risk of recurrent cardiovascular events among patients with a baseline LDL-C ≥ 100 mg/dL. Further studies need to confirm that CSL112 efficacy is influenced by baseline LDL-C.