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

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

Abstract

Aims: The aim of this study was to evaluate the haemodynamic effects of serelaxin (30 µg/kg/day 20-h infusion and 4-h post-infusion period) in patients with acute heart failure (AHF).

Methods and results: 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.

Conclusion: 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. ClinicalTrials.gov identifier NCT01543854.

Keywords: Acute heart failure; Clinical trial; Haemodynamics; Serelaxin.

Figures

Figure 1
Figure 1
Patient disposition. *Between Day 3 and Day 30 for all three patients.
Figure 2
Figure 2
Effects on haemodynamic indices during the course of study in both treatment groups. Data presented as means ± standard error.
Figure 3
Figure 3
Effects on selected parameters of renal function in both treatment groups. Data presented as means ± standard error.

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