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

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 m2 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 serelaxinhad a significantly higher decrease in peak PCWP during the first 8 h of infusion (difference vs. placebo: −2.44 mmHg, P = 0.004). Serelaxinshowed 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 serelaxininfusion (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 serelaxinvs. placeboand treatment differences reached statistical significance at some time points. Serelaxinadministration improved renal function and decreased N-terminal pro- brain natriuretic peptidelevels vs. placebo. Treatment with serelaxinwas well tolerated with no apparent safety concerns. Conclusion The haemodynamic effects of serelaxinobserved 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][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01543854&atom=%2Fehj%2F35%2F7%2F431.atom