From the Duke Clinical Research Institute, Duke University School of Medicine, Durham (R.H.M., J.D.L., J.M., A.W., R.W.H., J.H.L., K.J.A., J.H.A.), and Tenax Therapeutics, Morrisville (R.J., D.H.) - both in North Carolina; the Canadian VIGOUR (Virtual Coordinating Centre for Global Collaborative Cardiovascular Research) Centre, University of Alberta, Edmonton (S.D., S.G.G.), Sunnybrook Health Sciences Centre, Toronto (S.F.), the Quebec Heart and Lung Institute, Quebec (D.K.), London Health Sciences Centre, London, ON (D.N.), and the Victoria Heart Institute Foundation, Victoria, BC (J.B.) - all in Canada; Cleveland Clinic Foundation (A.D., E.G.S.) and University Hospitals Cleveland Medical Center (S.P.) - both in Cleveland; Franciscan Health System, Tacoma, WA (J.L.); Columbia University Medical Center, New York (M.A.); Spectrum Health, Grand Rapids, MI (E.M.); the Heart Hospital Baylor Plano, Plano, TX (R.M.); the Medical University of Graz, Graz, Austria (W.T.); the University of Luebeck, Luebeck, Germany (M.H.); and the Department of Medicine, Stanford University, Stanford, CA (R.A.H.).
N Engl J Med. 2017 May 25;376(21):2032-2042. doi: 10.1056/NEJMoa1616218. Epub 2017 Mar 19.
Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after cardiac surgery.
In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of levosimendan in patients with a left ventricular ejection fraction of 35% or less who were undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients were randomly assigned to receive either intravenous levosimendan (at a dose of 0.2 μg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 μg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery. The two primary end points were a four-component composite of death through day 30, renal-replacement therapy through day 30, perioperative myocardial infarction through day 5, or use of a mechanical cardiac assist device through day 5; and a two-component composite of death through day 30 or use of a mechanical cardiac assist device through day 5.
A total of 882 patients underwent randomization, 849 of whom received levosimendan or placebo and were included in the modified intention-to-treat population. The four-component primary end point occurred in 105 of 428 patients (24.5%) assigned to receive levosimendan and in 103 of 421 (24.5%) assigned to receive placebo (adjusted odds ratio, 1.00; 99% confidence interval [CI], 0.66 to 1.54; P=0.98). The two-component primary end point occurred in 56 patients (13.1%) assigned to receive levosimendan and in 48 (11.4%) assigned to receive placebo (adjusted odds ratio, 1.18; 96% CI, 0.76 to 1.82; P=0.45). The rate of adverse events did not differ significantly between the two groups.
Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo among patients with a reduced left ventricular ejection fraction who were undergoing cardiac surgery with the use of cardiopulmonary bypass. (Funded by Tenax Therapeutics; LEVO-CTS ClinicalTrials.gov number, NCT02025621 .).
左西孟旦是一种正性肌力药物，小型研究表明其可预防或治疗体外循环心脏手术后的低心排血量综合征。
在一项多中心、随机、安慰剂对照、3 期临床试验中，我们评估了左西孟旦在左心室射血分数为 35%或更低且接受体外循环心脏手术的患者中的疗效和安全性。患者被随机分配接受静脉注射左西孟旦（起始剂量为 0.2μg/kg/分钟，持续 1 小时，随后 0.1μg/kg/分钟，持续 23 小时）或安慰剂，在手术前开始输注。两个主要终点是 30 天内死亡、30 天内肾脏替代治疗、5 天内心肌梗死或 5 天内心脏机械辅助装置的使用组成的 4 项复合终点；以及 30 天内死亡或 5 天内心脏机械辅助装置的使用组成的 2 项复合终点。
共 882 例患者进行了随机分组，其中 849 例接受左西孟旦或安慰剂治疗，并纳入改良意向治疗人群。4 项复合主要终点在 428 例接受左西孟旦治疗的患者中有 105 例（24.5%）和 421 例接受安慰剂治疗的患者中有 103 例（24.5%）发生（调整后的优势比，1.00；99%置信区间[CI]，0.66 至 1.54；P=0.98）。2 项复合主要终点在 428 例接受左西孟旦治疗的患者中有 56 例（13.1%）和 421 例接受安慰剂治疗的患者中有 48 例（11.4%）发生（调整后的优势比，1.18；96%CI，0.76 至 1.82；P=0.45）。两组不良事件发生率无显著差异。
在接受体外循环心脏手术的左心室射血分数降低的患者中，预防性左西孟旦并未降低短期复合终点（死亡、肾脏替代治疗、围手术期心肌梗死或使用机械心脏辅助装置）的发生率，该复合终点的发生率与安慰剂组无差异。（由 Tenax Therapeutics 资助；LEVO-CTS ClinicalTrials.gov 编号，NCT02025621）。
