A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure

作者：Ponikowski Piotr^*; Mitrovic Veselin; Ruda Mikhail; Fernandez Alberto; Voors Adriaan A; Vishnevsky Alexander; Cotter Gad; Milo Olga; Laessing Ute; Zhang Yiming; Dahlke Marion; Zymlinski Robert; Metra Marco

来源：European Heart Journal, 2014, 35(7): 431-441.

DOI：10.1093/eurheartj/eht459

• Serelaxin
• Acute heart failure
• Haemodynamics
• Clinical trial

The aim of this study was to evaluate the haemodynamic effects of serelaxin (30 g/kg/day 20-h infusion and 4-h post-infusion period) in patients with acute heart failure (AHF). %26lt;br%26gt;This double-blind, multicentre study randomized 71 AHF patients with pulmonary capillary wedge pressure (PCWP) 18 mmHg, systolic blood pressure (BP) 115 mmHg, and estimated glomerular filtration rate 30 mL/min/1.73 m(2) to serelaxin (n 34) or placebo (n 37) within 48 h of hospitalization. Co-primary endpoints were peak change from baseline in PCWP and cardiac index (CI) during the first 8 h of infusion. Among 63 patients eligible for haemodynamic analysis (serelaxin, n 32; placebo, n 31), those treated with serelaxin had a significantly higher decrease in peak PCWP during the first 8 h of infusion (difference vs. placebo: 2.44 mmHg, P 0.004). Serelaxin showed no significant effect on the peak change in CI vs. placebo. Among secondary haemodynamic endpoints, a highly significant reduction in pulmonary artery pressure (PAP) was observed throughout the serelaxin infusion (largest difference in mean PAP vs. placebo: 5.17 mmHg at 4 h, P 0.0001). Right atrial pressure, systemic/pulmonary vascular resistance, and systolic/diastolic BP decreased from baseline with serelaxin vs. placebo and treatment differences reached statistical significance at some time points. Serelaxin administration improved renal function and decreased N-terminal pro-brain natriuretic peptide levels vs. placebo. Treatment with serelaxin was well tolerated with no apparent safety concerns. %26lt;br%26gt;The haemodynamic effects of serelaxin observed in the present study provide plausible mechanistic support for improvement in signs and symptoms of congestion observed with this agent in AHF patients. %26lt;br%26gt;ClinicalTrials.gov identifier NCT01543854.

• 出版日期2014-2