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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.).
Insights
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.
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.
Background:
Cardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein - has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear.
Methods:
We conducted an international, double-blind, placebo-controlled trial involving patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors. Patients were randomly assigned to receive either four weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for the acute myocardial infarction. The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes from randomization through 90 days of follow-up.
Results:
A total of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in the placebo group). There was no significant difference between the groups in the risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.05; P = 0.24), at 180 days of follow-up (622 patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01), or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events was similar in the two groups; a higher number of hypersensitivity events was reported in the CSL112 group.
Conclusions:
Among patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days. (Funded by CSL Behring; AEGIS-II ClinicalTrials.gov number, NCT03473223.).
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