Herzzentrum der Universität zu Köln, Cologne, Germany.
Eur Heart J. 2013 Jan;34(1):57-67. doi: 10.1093/eurheartj/ehs196. Epub 2012 Jul 9.
Cinaciguat (BAY 58-2667) is a novel soluble guanylate cyclase activator. This study evaluated the haemodynamic effect and safety of cinaciguat added to standard therapy in patients with acute decompensated heart failure (ADHF).
In this placebo-controlled, phase IIb study (NCT00559650), 139 patients admitted with ADHF, pulmonary capillary wedge pressure (PCWP) ≥18 mmHg, left ventricular ejection fraction <40%, and a pre-existing need for invasive haemodynamic monitoring were randomized 2:1 to cinaciguat:placebo (continuous i.v. infusion). The dose was titrated for 8 h and maintained for 16-40 h (starting dose: 100 μg/h). At 8 h, mean PCWP changed from 25.7 ± 5.0 mmHg by -7.7 mmHg with cinaciguat and from 25.0 ± 5.3 mmHg by -3.7 mmHg with placebo (P < 0.0001). The mean right atrial pressure changed from 12.4 ± 5.3 mmHg by -2.7 mmHg with cinaciguat and from 11.8 ± 4.9 mmHg by -0.6 mmHg with placebo (P= 0.0019). Cinaciguat also decreased the pulmonary and systemic vascular resistance and the mean arterial pressure, and increased the cardiac index (all P < 0.0001 vs. placebo). Systolic blood pressure changed by -21.6 ± 17.0 mmHg with cinaciguat and -5.0 ± 14.5 mmHg with placebo. Adverse events were experienced by 71 and 45% of patients receiving cinaciguat and placebo, respectively. No adverse effects on the 30-day mortality were seen; however, the trial was stopped prematurely due to an increased occurrence of hypotension at cinaciguat doses ≥200 µg/h.
Cinaciguat unloaded the heart in patients with ADHF. However, high doses were associated with hypotension.
西那卡塞（BAY 58-2667）是一种新型可溶性鸟苷酸环化酶激活剂。本研究评估了西那卡塞联合标准治疗对急性失代偿性心力衰竭（ADHF）患者的血流动力学效应和安全性。
在这项安慰剂对照、IIb 期研究（NCT00559650）中，139 名因 ADHF 入院、肺毛细血管楔压（PCWP）≥18mmHg、左心室射血分数<40%且需要进行侵入性血流动力学监测的患者，按 2:1 随机分为西那卡塞：安慰剂（连续静脉输注）组。在 8 小时内进行滴定剂量，然后维持 16-40 小时（起始剂量：100μg/h）。在 8 小时时，西那卡塞组的平均 PCWP 从 25.7±5.0mmHg 降低了-7.7mmHg，而安慰剂组从 25.0±5.3mmHg 降低了-3.7mmHg（P<0.0001）。西那卡塞组的平均右心房压从 12.4±5.3mmHg 降低了-2.7mmHg，而安慰剂组从 11.8±4.9mmHg 降低了-0.6mmHg（P=0.0019）。西那卡塞还降低了肺血管阻力、全身血管阻力和平均动脉压，并增加了心指数（均 P<0.0001 与安慰剂相比）。西那卡塞组的收缩压降低了-21.6±17.0mmHg，而安慰剂组降低了-5.0±14.5mmHg。接受西那卡塞和安慰剂的患者分别有 71%和 45%发生不良事件。未观察到 30 天死亡率的不良影响；然而，由于西那卡塞剂量≥200μg/h 时低血压的发生率增加，该试验提前终止。
西那卡塞使 ADHF 患者心脏负荷减轻。然而，高剂量与低血压有关。
