Serelaxin improves renal plasma flow in chronic heart failure
Presented at the Heart Failure Society of America Meeting
Patients with chronic heart failure have an improved renal plasma flow after treatment with serelaxin, as is shown in the small randomised RELAX-AHF study.
Serelaxin is a peptide hormone that relaxes blood vessels, thereby improving blood flow to the organs. It is derived from relaxin, a naturally occurring hormone mostly associated with pregnancy, although men also express it.
Patients receiving serelaxin (n=28) showed an increase in renal plasma flow of 29% over 8-24 hours as opposed to baseline, while the increase in the placebo arm (n-37) was only 14% (P=0.038). Comparable differences were seen with regard to the increase in renal plasma flow over 0-24 hours (31% vs 13% in placebo, P=0.004) and over 24-48 hours (35% vs. 16%, P=0.011).
These results suggest that patients with acute heart failure with renal failure can benefit from serelaxin. A subgroup analysis of the phase II Pre-RELAX-AHF and the phase III RELAX-AHF studies showed that serelaxin was associated with lower serum creatinin and plasma cystatin-C values in the first five days after enrolment, and with a lower incidence of worsening renal function on day two.
A more recent subgroup analysis of the phase III study showed a larger decrease of cardiovascular mortality and all-cause mortality in those patients in the treatment arm who had an estimated glomerular filtration rate (eGFR) lower than 50 mL/min/m2, as compared to placebo.
The current study was set up in response to the evidence of possible benefits for renal function. No difference was seen in the co-primary endpoint eGRF, at any time. Because renal plasma flow was higher in the serelaxin arm, this group had a lower calculated filtration fraction (P=0.002), which suggests a lower glomerular pressure.
Serelaxin had no effect on systolic blood pressure, but it did result in a significantly lower diastolic blood pressure. Urinary sodium excretion was not altererd.
Although increased GFR and/or sodium excretion would have been welcomed, these findings point to benefits of serelaxin for renal haemodynamics in patients with chronic heart failure.