Table 1.

Summary of post-hoc analyses of RELAX-AHF

Study, year	Topic of investigation	Results	Notes	Ref.
Metra et al, Jan 2013	Biomarkers of organ damage in patients with acute heart failure	Improvement in cardiac (troponin T), renal (creatinine and cystatin-C) and liver (ALT, AST) biomarkers upon administration of serelaxin, correlating with reduced 180-day mortality		[75]
Metra et al, Oct 2013	Assessment of dyspnea relief, CV and 180-day mortality in patient sub-groups with AHF upon treatment with serelaxin	Forest plots of subgroup analyses show no subgroup based variations in dyspnea relief upon treatment. CV mortality was reduced in patients ≥ 75 years (P=0.0337), and with no HF hospitalization in previous year (P = 0.0119), no baseline beta blocker use (P=0.0432) and with ≤12% blood lymphocytes (P = 0.0137) and eGFR < 50 ml/min/m2 (P=0.0286). Similar subgroup based trends observed in 180 day all-cause mortality reductions	Pre-defined subgroups: demographic (age, race, sex, region), time from presentation to randomization, eGFR, SBP, past medical history (AF, diabetes, ischemic heart disease, cardiac devices and i.v. adminstration at the time of randomization)	[76]
Filippatos et al, Apr 2014	Response of AHF patients with HFpEF to serelaxin treatment	Serelaxin well tolerated in patients with HFpEF. Dyspnea relief measured via VAS-AUC was similar to observed results in patients with HFrEF; however, Likert scale results for moderate or marked dyspnea improvement at 6,12 and 24 hours show difference in effects, with increased odds ratio for improvement in patients with HFpEF (P=0.03). Survival outcomes were similar in both groups	26% of recruited patients in RELAX-AHF had HFpEF	[77]
Cotter et al, Nov 2015	Association of growth differentiation factor – 15 (GDF 15) levels with RELAX AHF end points	Large increase in GDF-15 associated with higher risk of 60 and 180-day CV mortality. Randomization to serelaxin treatment correlated with decrease in GDF-15 levels at days 2 and 5.	GDF-15 is a member of the TGF-ß super family, and is associated with poor outcomes in chronic heart failure	[78]
Liu et al, Sept 2016	Effect of treatment with serelaxin on renal function	Renal impairment was defined in patients with an eGFR < 60 ml/min/1.73 m2. Renally impaired patients on serelaxin had further all-cause mortality reduction (HR 0.53, 95% CI 0.34–0.83), compared to patients without impairment (HR 1.30, 95% CI 0.51–3.29)	Renal dysfunction led to an overall increase in CV and all-cause mortality in RELAX AHF	[79]
Filippatos et al, Feb 2017	Assessment of RELAX-AHF endpoints in patients with and without AF	Serelaxin demonstrated similar efficacy and safety profile in patients with and without atrial fibrillation. Although stroke incidence was higher in AF patients in general, a trend of lower incidence was observed in patients treated with serelaxin (OR 0.31, P=0.0759) versus placebo (OR 3.88, P=0.2255; interaction P=0.0518)		[80]