急性心肌梗死患者经皮冠状动脉介入治疗前的环孢素。
Cyclosporine before PCI in Patients with Acute Myocardial Infarction.
机构信息
From Centre Hospitalier Universitaire (CHU) Arnaud de Villeneuve (T.-T.C.) and Clinique du Millénaire (C.P.), Montpellier, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Strasbourg (O.M.), CHU de Nimes, Nimes (G.C.), Hôpital Cardiovasculaire Louis Pradel (G. Rioufol, E.B.-C., C.B., I.B., C.J., G.D., N.M., M.O.), Claude Bernard University (G. Rioufol, E.B.-C., C.B., I.B., C.J., G.D., N.M., M.O.), Centre Hospitalier Saint-Joseph et Saint-Luc (J.-F.A.), Clinique de la Sauvegarde (V.M.), Clinique du Tonkin (P.S.), Clinical Investigation Center and Explorations Fonctionnelles Cardiovasculaires (C.B., I.B., C.J., G.D., N.M., M.O.), Lyon, CHU de Tours (D.A.) and Clinique Saint-Gatien (D.B.), Tours, Hôpital Guillaume et René Laennec, Nantes (P.G.), CHU de Rangueil, Toulouse (M.E.), Centre Hospitalier de Pau, Pau (N.D.), Hôpital Haut Lévèque, Bordeaux (P. Coste), Hôpital A. Michallon-CHU de Grenoble, Grenoble (G.V.), Hôpital Henri Duffau, Avignon (M.M.), Centre Hospitalier du Pays d'Aix, Aix-en-Provence (B.J.), Hôpital Gabriel Montpied, Clermont Ferrand (P.M.), Hôpital Charles Nicolle, Rouen (C.T.), Clinique de la Fourcade, Bayonne (J.-N.L.), Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris (P.G.S.), Hôpital du Bocage, Dijon (Y.C.), Centre Hospitalier General, Chartres (G. Range), Centre Hospitalier de Compiègne, Compiègne (J.C.), CHU d'Angers, Angers (F.P.), CHU de Nancy-Brabois, Vandœuvre-lès-Nancy (F.M.), CHU de Mulhouse (O.R.) and Clinique du Diaconat (O.I.), Mulhouse, Centre Hospitalier d'Annecy, Annecy (L.B.), Polyclinique des Fleurs, Ollioules (P.B.), Hôpital de La Cavale Blanche, Brest (M.G.), Clinique Esquirol, Agen (P. Colin, F.D.P.), Institut Jacques Cartier, Massy (M.-C.M.), Centre Hospitalier Henri Mondor, Créteil (J.-L.D.-R.), Hôpital Claude Galien, Quincy sous Sénat (T.U.), Hôpital Pontchaillou, Rennes (H.L.B.), Clinique de l'Ormeau, Tarbes (T.B.), Hôpital de la Côte de Nacre, Caen (G.G.), and Hôpital Cardi
出版信息
N Engl J Med. 2015 Sep 10;373(11):1021-31. doi: 10.1056/NEJMoa1505489. Epub 2015 Aug 30.
BACKGROUND
Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling.
METHODS
In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume.
RESULTS
A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups.
CONCLUSIONS
In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).
背景
实验和临床证据表明，环孢素可能减轻再灌注损伤并减少心肌梗死面积。我们旨在检验环孢素是否会改善临床结局并预防不良的左心室重构。
方法
在一项多中心、双盲、随机试验中，我们将 970 例急性前壁 ST 段抬高型心肌梗死（STEMI）患者纳入研究，这些患者在症状发作后 12 小时内行经皮冠状动脉介入治疗（PCI），且罪犯冠状动脉完全闭塞。患者在冠状动脉再通前接受静脉注射环孢素（剂量为 2.5mg/kg 体重）或匹配安慰剂的负荷剂量注射。主要终点为 1 年时的任何原因死亡、初始住院期间心力衰竭恶化、因心力衰竭再次住院或不良的左心室重构复合终点。不良的左心室重构定义为左心室舒张末期容积增加 15%或以上。
结果
环孢素组 395 例患者和安慰剂组 396 例患者接受了分配的研究药物治疗，并且在 1 年时可评估主要终点数据。环孢素组和对照组的主要终点发生率分别为 59.0%和 58.1%（比值比，1.04；95%置信区间[CI]，0.78 至 1.39；P=0.77）。环孢素并未降低主要终点的各单独临床组分发生率或其他事件发生率，包括再发梗死、不稳定型心绞痛和卒中等。两组治疗的安全性特征无显著差异。
结论
对于接受直接 PCI 的前壁 STEMI 患者，静脉注射环孢素并未改善临床结局，与安慰剂相比，1 年时也未预防不良的左心室重构。（由法国卫生部和 NeuroVive 制药公司资助；CIRCUS ClinicalTrials.gov 编号，NCT01502774；EudraCT 编号，2009-013713-99.）
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