TY - JOUR
T1 - Effect of Reconstituted Human Apolipoprotein A-I on Recurrent Ischemic Events in Survivors of Acute MI
AU - Povsic, Thomas J.
AU - Korjian, Serge
AU - Bahit, M. Cecilia
AU - Chi, Gerald
AU - Duffy, Danielle
AU - Alexander, John H.
AU - Vinereanu, Dragos
AU - Tricoci, Pierluigi
AU - Mears, Sojaita Jenny
AU - Deckelbaum, Lawrence I.
AU - Bonaca, Marc
AU - Ridker, Paul M.
AU - Goodman, Shaun G.
AU - Cornel, Jan H.
AU - Lewis, Basil S.
AU - Parkhomenko, Alexander
AU - Lopes, Renato D.
AU - Aylward, Philip
AU - Lincoff, A. Michael
AU - Heise, Mark
AU - Sacks, Frank
AU - Nicolau, Jose C.
AU - Merkely, Bela
AU - Trebacz, Jaroslaw
AU - Libby, Peter
AU - Nicholls, Stephen J.
AU - Pocock, Stuart
AU - Bhatt, Deepak L.
AU - Kastelein, John
AU - Bode, Christoph
AU - Mahaffey, Kenneth W.
AU - Steg, P. Gabriel
AU - Tendera, Michal
AU - Bainey, Kevin R.
AU - Harrington, Robert A.
AU - Mehran, Roxana
AU - Duerschmied, Daniel
AU - Kingwell, Bronwyn A.
AU - Gibson, C. Michael
AU - AEGIS-II Committees and Investigators
PY - 2024/6/4
Y1 - 2024/6/4
N2 - Background: The AEGIS-II trial hypothesized that CSL112, an intravenous formulation of human apoA-I, would lower the risk of plaque disruption, decreasing the risk of recurrent events such as myocardial infarction (MI) among high-risk patients with MI.Objectives: This exploratory analysis evaluates the effect of CSL112 therapy on the incidence of cardiovascular (CV) death and recurrent MI.Methods: The AEGIS-II trial was an international, multicenter, randomized, double-blind, placebo-controlled trial that randomized 18,219 high-risk acute MI patients to 4 weekly infusions of apoA-I (6 g CSL112) or placebo.Results: The incidence of the composite of CV death and type 1 MI was 11% to 16% lower in the CSL112 group over the study period (HR: 0.84; 95% CI: 0.7-1.0; P = 0.056 at day 90; HR: 0.86; 95% CI: 0.74-0.99; P = 0.048 at day 180; and HR: 0.89; 95% CI: 0.79-1.01; P = 0.07 at day 365). Similarly, the incidence of CV death or any MI was numerically lower in CSL112-treated patients throughout the follow-up period (HR: 0.92; 95% CI: 0.80-1.05 at day 90, HR: 0.89; 95% CI: 0.79-0.996 at day 180, HR: 0.91; 95% CI: 0.83-1.01 at day 365). The effect of CSL112 treatment on MI was predominantly observed for type 1 MI and type 4b (MI due to stent thrombosis).Conclusions: Although CSL112 did not significantly reduce the occurrence of the primary study endpoints, patients treated with CSL112 infusions had numerically lower rates of CV death and MI, type-1 MI, and stent thrombosis–related MI compared with placebo. These findings could suggest a role of apoA-I in reducing subsequent plaque disruption events via enhanced cholesterol efflux. Further prospective data would be needed to confirm these observations.
AB - Background: The AEGIS-II trial hypothesized that CSL112, an intravenous formulation of human apoA-I, would lower the risk of plaque disruption, decreasing the risk of recurrent events such as myocardial infarction (MI) among high-risk patients with MI.Objectives: This exploratory analysis evaluates the effect of CSL112 therapy on the incidence of cardiovascular (CV) death and recurrent MI.Methods: The AEGIS-II trial was an international, multicenter, randomized, double-blind, placebo-controlled trial that randomized 18,219 high-risk acute MI patients to 4 weekly infusions of apoA-I (6 g CSL112) or placebo.Results: The incidence of the composite of CV death and type 1 MI was 11% to 16% lower in the CSL112 group over the study period (HR: 0.84; 95% CI: 0.7-1.0; P = 0.056 at day 90; HR: 0.86; 95% CI: 0.74-0.99; P = 0.048 at day 180; and HR: 0.89; 95% CI: 0.79-1.01; P = 0.07 at day 365). Similarly, the incidence of CV death or any MI was numerically lower in CSL112-treated patients throughout the follow-up period (HR: 0.92; 95% CI: 0.80-1.05 at day 90, HR: 0.89; 95% CI: 0.79-0.996 at day 180, HR: 0.91; 95% CI: 0.83-1.01 at day 365). The effect of CSL112 treatment on MI was predominantly observed for type 1 MI and type 4b (MI due to stent thrombosis).Conclusions: Although CSL112 did not significantly reduce the occurrence of the primary study endpoints, patients treated with CSL112 infusions had numerically lower rates of CV death and MI, type-1 MI, and stent thrombosis–related MI compared with placebo. These findings could suggest a role of apoA-I in reducing subsequent plaque disruption events via enhanced cholesterol efflux. Further prospective data would be needed to confirm these observations.
KW - acute coronary syndrome
KW - apoA-I
KW - CSL112
KW - HDL
KW - myocardial infarction
KW - randomized clinical trial
KW - stent thrombosis
UR - http://www.scopus.com/inward/record.url?scp=85192081111&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2024.03.396
DO - 10.1016/j.jacc.2024.03.396
M3 - Article
C2 - 38588930
AN - SCOPUS:85192081111
SN - 0735-1097
VL - 83
SP - 2163
EP - 2174
JO - Journal of The American College of Cardiology
JF - Journal of The American College of Cardiology
IS - 22
ER -