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Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction.

C Michael Gibson1, Danielle Duffy1, Serge Korjian1

  • 1From the Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center (C.M.G., S.K., G.C.), and the Department of Medicine, Cardiovascular Division (P.L.), and the Center for Cardiovascular Disease Prevention (P.M.R.), Brigham and Women's Hospital (F.M.S.), Harvard Medical School, and the Harvard T.H. Chan School of Public Health (F.M.S.) - all in Boston; CSL Behring, King of Prussia, PA (D.D., M.H., P.T., L.I.D., S.J.M.); INECO Neurociencias, Rosario, Argentina (M.C.B.); Duke Clinical Research Institute, Duke Health, Durham, NC (J.H.A., R.D.L., T.J.P.); the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo (J.C.N.), and the Brazilian Clinical Research Institute (R.D.L.) - both in Sao Paulo; the Heart and Vascular Center of Semmelweis University, Budapest, Hungary (B.M.); Lady Davis Carmel Medical Center, Haifa, Israel (B.S.L.); Radboud University Medical Center, Nijmegen and Noordwest Ziekenhuisgroep, Alkmaar (J.H.C.), and the University of Amsterdam Academic Medical Center, Amsterdam (J.J.P.K.) - both in the Netherlands; Krakowski Szpital Specjalistyczny im. Jana Pawła II, Krakow (J.T.), and the Department of Cardiology and Structural Heart Disease, School of Medicine in Katowice, Medical University of Silesia, Katowice (M.T.) - both in Poland; the National Scientific Center, Kyiv, Ukraine (A.P.); the University of Colorado School of Medicine, Anschutz Medical Campus, Aurora (M.B.); the Canadian VIGOUR Centre, University of Alberta, Edmonton, and St. Michael's Hospital, Unity Health Toronto, and Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto - all in Canada (S.G.G.); Mount Sinai Fuster Heart Hospital (D.L.B.) and Zena and Michael A. Wiener Cardiovascular Institute (R.M.), Icahn School of Medicine at Mount Sinai, and Weill Cornell Medicine (R.A.H.) - both in New York; Université Paris-Cité, INSERM Unité 1148, FACT and Assistance Publique-Hopitaux de Paris, Hôpital Bichat, Paris (P.G.S.); South Australian Health and Medical Research Institute/SAHMRI, Adelaide, SA (P.A.), and Victorian Heart Institute, Monash University, Melbourne, VIC (S.J.N.) - both in Australia; the Heart Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (C.B.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); and London School of Hygiene and Tropical Medicine, London (S.J.P.).

The New England Journal of Medicine
|April 8, 2024
PubMed
Summary

CSL112 infusions did not reduce the risk of recurrent cardiovascular events after acute myocardial infarction. This study found no significant difference in major adverse cardiovascular events between CSL112 and placebo groups.

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Area of Science:

  • Cardiology
  • Biochemistry

Background:

  • Recurrent cardiovascular events are common after acute myocardial infarction.
  • Low cholesterol efflux, mediated by apolipoprotein A1 (ApoA1), is linked to increased cardiovascular risk.
  • CSL112, a plasma-derived human ApoA1, enhances cholesterol efflux capacity.

Purpose of the Study:

  • To evaluate the efficacy of CSL112 infusions in reducing recurrent cardiovascular events post-acute myocardial infarction.
  • To assess the safety profile of CSL112 in this patient population.

Main Methods:

  • An international, double-blind, placebo-controlled trial (AEGIS-II) was conducted.
  • 18,219 patients with acute myocardial infarction, multivessel coronary artery disease, and risk factors received four weekly infusions of CSL112 or placebo.
  • The primary endpoint was a composite of myocardial infarction, stroke, or cardiovascular death within 90 days.

Main Results:

  • No significant difference in the primary endpoint risk was observed at 90 days (4.8% vs. 5.2%), 180 days (6.9% vs. 7.6%), or 365 days (9.8% vs. 10.5%).
  • Hazard ratios for the primary endpoint were consistently near 1 across follow-up periods.
  • Adverse event rates were similar, with a noted increase in hypersensitivity events in the CSL112 group.

Conclusions:

  • Four weekly infusions of CSL112 did not significantly lower the risk of myocardial infarction, stroke, or cardiovascular death compared to placebo in high-risk patients post-acute myocardial infarction.
  • CSL112 did not demonstrate efficacy in preventing major adverse cardiovascular events within 90 days.
  • The study suggests CSL112 is not effective for secondary prevention of cardiovascular events in this context.