载脂蛋白 A1 输注与急性心肌梗死后的心血管结局。
Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction.
机构信息
From 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.).
出版信息
N Engl J Med. 2024 May 2;390(17):1560-1571. doi: 10.1056/NEJMoa2400969. Epub 2024 Apr 6.
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.).
背景
急性心肌梗死后常发生心血管事件，胆固醇外排能力降低-这一过程由载脂蛋白 A1 介导，载脂蛋白 A1 是高密度脂蛋白中的主要蛋白-与心血管事件风险增加有关。CSL112 是人载脂蛋白 A1 来源于血浆，可增加胆固醇外排能力。CSL112 输注是否能降低急性心肌梗死后复发性心血管事件的风险尚不清楚。
方法
我们进行了一项国际性、双盲、安慰剂对照试验，纳入了急性心肌梗死、多支冠状动脉疾病和其他心血管危险因素的患者。患者被随机分配接受 4 周 6 g CSL112 或匹配安慰剂治疗，首次输注在急性心肌梗死后首次医疗接触后 5 天内进行。主要终点是随机分组至 90 天随访期间的心肌梗死、卒中和心血管原因死亡的复合终点。
结果
共纳入 18219 例患者（CSL112 组 9112 例，安慰剂组 9107 例）。两组 90 天随访时主要终点事件的风险无显著差异（CSL112 组 439 例[4.8%] vs. 安慰剂组 472 例[5.2%]；风险比，0.93；95%置信区间[CI]，0.81 至 1.05；P=0.24），180 天随访时（CSL112 组 622 例[6.9%] vs. 安慰剂组 683 例[7.6%]；风险比，0.91；95%CI，0.81 至 1.01）和 365 天随访时（CSL112 组 885 例[9.8%] vs. 安慰剂组 944 例[10.5%]；风险比，0.93；95%CI，0.85 至 1.02）。两组不良事件发生率相似；CSL112 组报告的过敏反应事件较多。
结论
在急性心肌梗死、多支冠状动脉疾病和其他心血管危险因素的患者中，与安慰剂相比，每周 4 次输注 CSL112 并未降低 90 天内心肌梗死、卒中和心血管原因死亡的风险。（由 CSL Behring 资助；AEGIS-II ClinicalTrials.gov 编号，NCT03473223。）
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