Gad Cotter1, Adriaan A Voors2, Margaret F Prescott3, G Michael Felker4, Gerasimos Filippatos5, Barry H Greenberg6, Peter S Pang7, Piotr Ponikowski8, Olga Milo1, Tsushung A Hua3, Min Qian9, Thomas M Severin3, John R Teerlink10, Marco Metra11, Beth A Davison1. 1. Momentum Research Inc, 3100 Tower Boulevard, Durham, NC, 27707, USA. 2. University Medical Centre Groningen, Groningen, the Netherlands. 3. Novartis Pharmaceuticals Corporation, New Hanover, NJ, USA. 4. Duke Clinical Research Institute, Durham, NC, USA. 5. Athens University Hospital, Attikon, Athens, Greece. 6. University of California at San Diego, San Diego, CA, USA. 7. Indiana University School of Medicine, Indianapolis, IN, USA. 8. Medical University, Clinical Military Hospital, Wroclaw, Poland. 9. Columbia University, New York, NY, USA. 10. University of California-San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA. 11. University of Brescia, Brescia, Italy.
Abstract
BACKGROUND:Growth differentiation factor 15 (GDF-15) was found to be upregulated in patients with chronic heart failure (HF) and associated with disease severity, however, data on patients with acute heart failure (AHF) is lacking. METHODS AND RESULTS:Levels of GDF-15 were measured at pre-specified time-points (baseline and at days 2, 5, 14, and 60) in patients enrolled in the placebo-controlled RELAXin in Acute Heart Failure (RELAX-AHF) study, which examined the effect of serelaxin in 1161 patients with AHF, systolic blood pressure >125 mmHg, and mild to moderate renal impairment. Neither baseline nor changes in GDF-15 were associated with the degree of dyspnoea or dyspnoea relief. After adjustment for baseline characteristics, baseline GDF-15 was not associated with the composite endpoint of heart failure or renal failure (HF/RF) readmission at 60 days/cardiovascular (CV) death or CV death at 180 days. In contrast, larger increases in GDF-15 levels at days 2 and 14 were associated with a greater risk of 60-day HF/RF rehospitalizations/CV death and CV death at 180 days. Serelaxin treatment was associated with significantly larger decreases of GDF-15 at days 2 and 5 than placebo. CONCLUSIONS: In AHF patients enrolled in the RELAX-AHF study, increases in GDF-15 levels, but not baseline measurements, were associated with a greater likelihood of adverse outcomes. Serelaxin administration was associated with greater decreases in GDF-15 compared with placebo.
RCT Entities:
BACKGROUND:Growth differentiation factor 15 (GDF-15) was found to be upregulated in patients with chronic heart failure (HF) and associated with disease severity, however, data on patients with acute heart failure (AHF) is lacking. METHODS AND RESULTS: Levels of GDF-15 were measured at pre-specified time-points (baseline and at days 2, 5, 14, and 60) in patients enrolled in the placebo-controlled RELAXin in Acute Heart Failure (RELAX-AHF) study, which examined the effect of serelaxin in 1161 patients with AHF, systolic blood pressure >125 mmHg, and mild to moderate renal impairment. Neither baseline nor changes in GDF-15 were associated with the degree of dyspnoea or dyspnoea relief. After adjustment for baseline characteristics, baseline GDF-15 was not associated with the composite endpoint of heart failure or renal failure (HF/RF) readmission at 60 days/cardiovascular (CV) death or CV death at 180 days. In contrast, larger increases in GDF-15 levels at days 2 and 14 were associated with a greater risk of 60-day HF/RF rehospitalizations/CV death and CV death at 180 days. Serelaxin treatment was associated with significantly larger decreases of GDF-15 at days 2 and 5 than placebo. CONCLUSIONS: In AHF patients enrolled in the RELAX-AHF study, increases in GDF-15 levels, but not baseline measurements, were associated with a greater likelihood of adverse outcomes. Serelaxin administration was associated with greater decreases in GDF-15 compared with placebo.
Authors: Frank Kramer; Hani N Sabbah; James J Januzzi; Faiez Zannad; J Peter van Tintelen; Erik B Schelbert; Raymond J Kim; Hendrik Milting; Richardus Vonk; Brien Neudeck; Richard Clark; Klaus Witte; Wilfried Dinh; Burkert Pieske; Javed Butler; Mihai Gheorghiade Journal: Heart Fail Rev Date: 2017-05 Impact factor: 4.214
Authors: Balaji K Tamarappoo; Andrew Lin; Frederic Commandeur; Priscilla A McElhinney; Sebastien Cadet; Markus Goeller; Aryabod Razipour; Xi Chen; Heidi Gransar; Stephanie Cantu; Robert Jh Miller; Stephan Achenbach; John Friedman; Sean Hayes; Louise Thomson; Nathan D Wong; Alan Rozanski; Piotr J Slomka; Daniel S Berman; Damini Dey Journal: Atherosclerosis Date: 2020-11-13 Impact factor: 5.162