Results of the RELAX-AHF trial are grounds for cautious optimism.
Persistently high hospitalization rates for acute heart failure (HF) have not given rise to effective new treatment strategies — although certainly not for lack of effort (JW Cardiol Jul 6 2011, Nov 14 2007, and Apr 4 2007). Serelaxin, a recombinant vasoactive peptide, was recently the subject of an intriguing phase II study (JW Cardiol Apr 1 2009). Now, the RELAX-AHF investigators present results of a manufacturer-sponsored, double-blinded study in 1161 patients with acute HF (mean age, 72; 55% with at least moderate left ventricular systolic dysfunction). All participants had dyspnea, radiographic pulmonary edema, elevated N-terminal-pro–B-type natriuretic peptide levels, and mild or moderate renal dysfunction. Exclusion criteria included systolic blood pressure 125 mm Hg, intravenous HF medications (aside from diuretics or nitrates), mechanical support, and recent acute coronary syndrome. Patients were randomized to continuous infusion of serelaxin (30 µg/kg/day) or placebo for 48 hours.
The primary endpoints were two measures of dyspnea improvement. Compared with placebo, serelaxin significantly improved the area under the curve of a visual analog scale to 5 days (448 mm x h) but not the proportion of patients with at least moderate improvement on the Likert scale for 24 hours (27% vs. 26%). Numerous secondary endpoints (e.g., cardiovascular death or HF readmission, renal failure) did not differ between the groups; however, total mortality at 180 days was significantly lower with serelaxin than with placebo (42 [7.2%] vs. 65 [11.2%]).
Teerlink JR et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): A randomised, placebo-controlled trial. Lancet 2012 Nov 7; [e-pub ahead of print].
Konstam MA. RELAX-AHF: Rising from the doldrums in acute heart failure. Lancet 2012 Nov 7; [e-pub ahead of print].