背景:急性心肌梗死(AMI)后,患者仍存在随后发生心血管事件(CV)的风险.在AEGIS-II审判中,CSL112,一种来自血浆的人类载脂蛋白A-I,可增强胆固醇流出,并未显着减少CV死亡的首次发生,心肌梗死(MI),与安慰剂相比,90天或中风。然而,仅涉及第一个事件的分析可能无法捕获干预的临床影响的全部,因为患者可能经历多个事件.
目的:这项预设的探索性分析检查了CSL112对非致死性缺血事件总负担的影响(即,复发性MI和卒中)和CV死亡。
方法:共有18,219例AMI患者,多支冠状动脉疾病,和其他CV危险因素被随机分为每周4次输注6gCSL112(n=9,112)或匹配的安慰剂(n=9,107).负二项回归模型用于评估CSL112与安慰剂相比对缺血性事件发生率比(RR)的影响。
结果:对于CV死亡,MI,和中风,90天的总事件数量较少(503vs545事件;发生率[RR]:0.88;95%CI:0.76-1.03,P=0.11),名义上180天的总事件明显减少(745例vs821例,RR:0.87;95%CI:0.77-0.99;P=0.04)和365天(1,120对1,211事件;RR0.89;95%CI:0.80-0.99;P=0.04)。随后的事件占90天事件的13%,180天的17%,一年的22%。在非致命性MI和CV死亡的总发生率中也看到了类似的发现。当II型MI时,不太可能通过增强胆固醇流出来改善,被排除在外,在所有时间点,非致死性MI(不包括2型)和CV死亡的总发生率均名义上显著降低(90天:RR:0.81;95%CI:0.68-0.97;P=0.02;180天:RR:0.82;95%CI:0.71-0.95;P<0.01;365天:RR:0.86;95%CI:0.76-0.98;P=0.02).
结论:在这项AEGIS-II试验的预设探索性分析中,与安慰剂相比,在AMI后的高危患者中每周4次输注CSL112可显着降低180天和365天非致死性缺血事件和CV死亡的总负担。(AEGIS-II[研究CSL112在患有急性冠脉综合征的受试者中的研究];NCT03473223)。
BACKGROUND: Following an acute myocardial infarction (AMI), patients remain at risk for subsequent cardiovascular (CV) events. In the AEGIS-II trial, CSL112, a human apolipoprotein A-I derived from plasma that enhances cholesterol efflux, did not significantly reduce the first occurrence of CV death, myocardial infarction (MI), or stroke through 90 days compared with placebo. However, an analysis involving only the first event may not capture the totality of the clinical impact of an intervention because patients may experience multiple events.
OBJECTIVE: This prespecified exploratory analysis examines the effect of CSL112 on total burden of nonfatal ischemic events (ie, recurrent MI and stroke) and CV death.
METHODS: A total of 18,219 patients with AMI, multivessel coronary artery disease, and additional CV risk factors were randomized to either 4 weekly infusions of 6 g CSL112 (n = 9,112) or matching placebo (n = 9,107). A negative binomial regression model was applied to estimate the effect of CSL112 compared with placebo on the rate ratio (RR) of ischemic events.
RESULTS: For CV death, MI, and stroke, there were numerically fewer total events at 90 days (503 vs 545 events; rate ratio [RR]: 0.88; 95% CI: 0.76-1.03, P = 0.11), and nominally significantly fewer total events at 180 days (745 vs 821 events, RR: 0.87; 95% CI: 0.77-0.99; P = 0.04) and 365 days (1,120 vs 1,211 events; RR 0.89; 95% CI: 0.80-0.99; P = 0.04). Subsequent events constituted 13% of events at 90 days, 17% at 180 days, and 22% at 1 year. Similar findings were seen with the total occurrence of nonfatal MI and CV death. When type II MIs, unlikely to be modified by enhancing cholesterol efflux, were excluded, there were nominally significant reductions in the total occurrence of nonfatal MI (excluding type 2) and CV death at all timepoints (90 days: RR: 0.81; 95% CI: 0.68-0.97; P = 0.02; 180 days: RR: 0.82; 95% CI: 0.71-0.95; P < 0.01; 365 days: RR: 0.86; 95% CI: 0.76-0.98; P = 0.02).
CONCLUSIONS: In this prespecified exploratory analysis of the AEGIS-II trial, 4 weekly infusions of CSL112 among high-risk patients after AMI significantly reduced the total burden of nonfatal ischemic events and CV death at 180 and 365 days compared with placebo. (AEGIS-II [Study to Investigate CSL112 in Subjects With Acute Coronary Syndrome]; NCT03473223).