ST 段抬高型心肌梗死中白细胞介素-1 阻断治疗时间的临床和药理学意义。
Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction.
机构信息
VCU Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, West Hospital, Richmond, Virginia (M.G.D.B., J.I.D., F.M., J.G.C., R.M., J.T., C.R.T., M.C.K., C.S.R., B.W.V.T., A.A.); Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (M.G.D.B.); Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy (M.G.D.B.); Interventional Cardiology Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina (J.I.D., J.G.C.); Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia (A.A.); Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia (L.K.); Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy (G.B.-Z.); Mediterranea Cardiocentro, Napoli, Italy (G.B.-Z.); and Department of Pharmacotherapy and Outcomes Science, MedStar Washington Hospital Center, Washington, DC (B.W.V.T.).
VCU Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, West Hospital, Richmond, Virginia (M.G.D.B., J.I.D., F.M., J.G.C., R.M., J.T., C.R.T., M.C.K., C.S.R., B.W.V.T., A.A.); Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (M.G.D.B.); Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy (M.G.D.B.); Interventional Cardiology Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina (J.I.D., J.G.C.); Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia (A.A.); Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia (L.K.); Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy (G.B.-Z.); Mediterranea Cardiocentro, Napoli, Italy (G.B.-Z.); and Department of Pharmacotherapy and Outcomes Science, MedStar Washington Hospital Center, Washington, DC (B.W.V.T.)
出版信息
J Pharmacol Exp Ther. 2023 Aug;386(2):156-163. doi: 10.1124/jpet.123.001601. Epub 2023 Apr 10.
Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has been shown to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI. We sought to determine whether time-to-treatment influences the efficacy of anakinra on systemic inflammation and incidence of HF events in patients with STEMI. We divided the cohort in two groups base6d on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF. We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271 (182-391) minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with time from PCI to treatment <271 minutes (222.6 [103.9-325.2] vs. 78.4 [44.3-131.2], < 0.001) and those with time from PCI to treatment ≥271 minute (235.2 [131.4-603.4] vs. 75.5 [38.9-171.9], < 0.001) ( > 0.05 for interaction). Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment <271 minutes (5 [11%] vs. 9n[36%], log-rank 5.985, = 0.014) as well as in patients with time from PCI to drug ≥271 minutes (2n[5%] vs. 7 [23%], log-rank 3.995, = 0.046) ( > 0.05 for interaction). IL-1 blockade with anakinra blunts the acute systemic inflammatory response and prevents HF events independent of time-to-treatment. SIGNIFICANCE STATEMENT: In patients with ST segment elevation presenting within 12 hours of pain onset and treated within 12 hours of reperfusion, interleukin-1 blockade with anakinra blunts the acute systemic inflammatory response, a surrogate of interleukin-1 activity, and prevents heart failure events independent of time-to-treatment.
白细胞介素-1 (IL-1) 阻断剂阿那白滞素在再灌注后 12 小时内给药，已被证明可减轻炎症反应，并可预防 STEMI 患者发生心力衰竭 (HF) 事件。我们试图确定治疗时间是否会影响阿那白滞素对 STEMI 患者全身炎症和 HF 事件发生率的疗效。我们根据经皮冠状动脉介入治疗 (PCI) 至研究药物的中位数时间将队列分为两组，并分析阿那白滞素对 C 反应蛋白 (CRP) 曲线下面积 (AUC-CRP) 和死亡或新发 HF 复合终点发生率的影响。我们分析了 139 名患者的数据：84 名（60%）接受阿那白滞素治疗，55 名（40%）接受安慰剂治疗。从 PCI 到研究治疗的中位时间为 271 分钟（182-391）。与安慰剂相比，阿那白滞素治疗患者的 AUC-CRP 明显升高，无论是 PCI 后治疗时间<271 分钟（222.6 [103.9-325.2] 与 78.4 [44.3-131.2]，<0.001）还是 PCI 后治疗时间≥271 分钟（235.2 [131.4-603.4] 与 75.5 [38.9-171.9]，<0.001）（交互作用>0.05）。阿那白滞素可显著降低 PCI 后治疗时间<271 分钟（5 [11%] 与 9n[36%]，log-rank 5.985，=0.014）以及 PCI 后治疗时间≥271 分钟（2n[5%] 与 7 [23%]，log-rank 3.995，=0.046）（交互作用>0.05）患者的死亡或新发 HF 复合终点事件。结论：在 ST 段抬高且胸痛发作 12 小时内且再灌注 12 小时内接受治疗的患者中，阿那白滞素阻断白细胞介素-1 可减轻急性全身炎症反应，这是白细胞介素-1 活性的替代指标，并可预防心力衰竭事件，与治疗时间无关。意义：在胸痛发作后 12 小时内接受治疗且再灌注 12 小时内接受治疗的 ST 段抬高患者中，阿那白滞素阻断白细胞介素-1 可减轻炎症反应，这是白细胞介素-1 活性的替代指标，并可预防心力衰竭事件，与治疗时间无关。
Zotero 插件