Apolipoprotein A-I infusions and cardiovascular outcomes in acute myocardial infarction according to baseline LDL-cholesterol levels: the AEGIS-II trial
C Michael Gibson, Danielle Duffy, M. Cecilia Bahit, Gerald Chi, Harvey White, Serge Korjian, John H. Alexander, A. Michael Lincoff, Mark Heise, Bronwyn A. Kingwell, José Carlos Nicolau, Renato D. Lópes, Jan H Cornel, Basil S. Lewis, Dragoş Vinereanu, Shaun G Goodman, Christoph Bode, Philippe Gabríel Steg, Peter Libby, Frank M. Sacks, Kevin R. Bainey, Paul M Ridker, Kenneth W. Mahaffey, Philip E. Aylward, Stephen J. Nicholls, Stuart Pocock, Roxana Mehran, Robert A. Harrington, C Michael Gibson, John H Alexander, Philip E. Aylward, Deepak L. Bhatt, Christoph Bode, Shaun G Goodman, Robert A. Harrington, Kenneth W. Mahaffey, A. Michael Lincoff, Roxana Mehran, Stephen J. Nicholls, Stuart Pocock, Paul M Ridker, Philippe Gabríel Steg, Michał Tendera, Danielle Duffy, Pierluigi Tricoci, C Michael Gibson, John H Alexander, John J.P. Kastelein, A. Michael Lincoff, Roxana Mehran, Stuart Pocock, Philippe Gabríel Steg, Danielle Duffy, C Michael Gibson, Cecilia Bahit, Gemma A. Figtree, Kurt Huber, Pascal Vranckx, Renato D. Lópes, José Carlos Nicolau, Nina Gotcheva, Kevin Bainey, Juan Carlos Prieto, Miguel Urina‐Triana, Miroslav Solař, Margus Viigimaa, Mika Laine, Gilles Montalescot, Tamaz Shaburishvili, Daniel Duerschmied, Dimitris Tousoulis, Michael Lee, Béla Merkely, Basil S. Lewis, Giuseppe Ambrosio, Ospedale S di Perugia, Satoshi Yasuda, Andrejs Ērglis, Rimvydas Šlapikas, Alan Yean Yip Fong, Jose Luis Leiva Pons, Jan H Cornel, Harvey White, Vibeke Juliebø, Manuel Horna, Jarosław Trębacz, João Morais, Dragoş Vinereanu, Sergey Zenin, Nebojša Tasić, Jack Tan, Jan Murin, Lesley Burgess, Hyun Jae Kang, Angel Cequier Fillat, Emil Hagström, Stephan Windecker, Jiunn-Lee Lin, Piyamitr Sritara, Ümit Güray
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 < 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.