Renal Hemodynamic Effects of Serelaxin in Patients With Chronic Heart Failure

Abstract

Background— Serelaxin is a promising therapy for acute heart failure. The renal hemodynamic effects of serelaxin in patients with chronic heart failure are unknown. Methods and Results— In this double-blind, randomized, placebo-controlled, multicenter study, patients with New York Heart Association Class II to III chronic heart failure, left ventricular ejection fraction ≤45%, and estimated glomerular filtration rate (GFR) 30 to 89 mL/min per 1.73 m 2 received intravenous serelaxin 30 μg/kg per day or placebo for 24 hours. Primarily, we assessed the difference between serelaxin and placebo on renal plasma flow (para-aminohippuric acid clearance) and GFR (iothalamate clearance) over 8 to 24 hours. All 22 patients from 1 clinical site were excluded from primary analyses before unblinding because of implausible measurements. The primary analysis comprised 65 patients, mean age was 68 (±10) years, 89% were male, mean estimated GFR was 64 (±19) mL/min per 1.73 m 2 , and 34% had New York Heart Association Class III symptoms. Renal plasma flow increased by 29% with serelaxin and 14% with placebo (13% relative increase with serelaxin; P =0.0386), whereas GFR changes did not differ significantly during 8 to 24 hours. Filtration fraction increased by 36% with serelaxin and 62% with placebo (16% relative decrease with serelaxin; P =0.0019) during 8 to 24 hours. Changes in systolic blood pressure were largely similar, and creatinine clearance did not differ between groups. Adverse event rates were similar with serelaxin (20.5%) and placebo (25.0%). Conclusions— In patients with chronic heart failure, serelaxin increased renal plasma flow and reduced the increase in filtration fraction compared with placebo, but did not affect GFR. These results suggest beneficial renal hemodynamic effects in patients with chronic heart failure. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01546532.

Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX‐AHF‐2 study

“…therapy are enrolled. The inclusion of at least mild renal dysfunction among the entry criteria allows selection of a higher‐risk patient population, where serelaxin's potential renoprotective properties could provide benefit 20, 25. Enrolling patients with normal‐to‐elevated blood pressure (SBP ≥125 mmHg) selects patients most likely to benefit from the vasodilatory properties of serelaxin and those less likely to suffer from the untoward effects of hypotension.…”

Serelaxin and acute heart failure

“…To further evaluate the potential beneficial renal haemodynamic effects of serelaxin, Voors et al enrolled 65 patients with New York Heart Association class II–III chronic heart failure, left ventricular ejection fraction (LVEF) ≤45% and eGFR 30–89 mL/min/1.73 m 2 , randomising them to intravenous serelaxin (30 µg/kg/day) or placebo for 24 h 19. Serelaxin resulted in a significant increase in renal plasma flow, compared with placebo, as well as a relative decrease in the increased filtration fraction and no change in creatinine clearance.…”

Serelaxin a novel treatment for acute heart failure

“…FF increased at all time points in both serelaxin and placebo group. However, the change observed with serelaxin was lower compared with placebo (16% relative decrease with serelaxin versus placebo; p = 0.0019) [35]. This may be one of the mechanisms that explain the renal-protective properties of serelaxin.…”