. 2019 Apr 26;35(4):558–564. doi: 10.1093/ndt/gfz058

Table 1.

Effect of kidney function on the efficacy of established treatments for chronic HFrEF

Trial (ref)	Intervention (sample size)	Main eligibility criteria	Follow-up (years)	Primary outcome	Overall treatment effect (95% CI)	CKD subgroups (eGFR, mL/min/ 1.73 m²)	Treatment effect in CKD	P for treatment × CKD interaction
ACEi
SOLVD-TREATMENT [31]	Enalapril versus placebo (n = 2569)	LVEF ≤35%; NYHA I–IV; creatinine <177 μmol/L	3.5	All-cause mortality	0.84 (0.74–0.95)	≥60 (n = 1466)	0.82 (0.69–0.98)	0.62
SOLVD-TREATMENT [31]	Enalapril versus placebo (n = 2569)	LVEF ≤35%; NYHA I–IV; creatinine <177 μmol/L	3.5	All-cause mortality	0.84 (0.74–0.95)	<60 (n = 1036)	0.88 (0.73–1.06)	0.62

β-blocker
CIBIS-II [32]	Bisoprolol versus placebo (n = 2647)	LVEF ≤35%; NYHA III–IV; creatinine <300 μmol/L	1.3	All-cause mortality	0.66 (0.54–0.81)	<45 (n = 450)	0.71 (0.48–1.05)	0.81
						≥45 <60 (n = 669)	0.69 (0.46–1.04)
						≥60 <75 (n = 640)	0.53 (0.34–0.82)
						>75 (n = 863)	0.64 (0.42–0.99)
MERIT-HF [33, 34]	Metoprolol versus placebo (n = 3991)	LVEF ≤40%; NYHA II–IV; ‘significant’ kidney disease	1	All-cause mortality	0.66 (0.53–0.81)	<45 (n = 493)	0.41 (0.25–0.68)	0.095
						≥45–≤60 (n = 976)	0.68 (0.45–1.02)
						>60 (n = 2496)	0.71 (0.54–0.95)
SENIORS [35, 36]	Nebivolol versus placebo (n = 2128)	LVEF <35% or hospitilization for decompensated HF; NYHA II–IV; creatinine <250 μmol/L	1.75	All-cause mortality or CV hospital admission	0.86 (0.74–0.99)	<55.5 (n = 704)	0.84 (0.67–1.07)	0.442
						55.5–72.8 (n = 704)	0.79 (0.60–1.04)
						>72.8 (n = 704)	0.86 (0.65–1.14)

Mineralocorticoid receptor antagonist
RALES [37, 38]	Spironolactone versus placebo (n = 1663)	LVEF <35%; NYHA III–IV; creatinine ≤221 μmol/L	2	All-cause mortality	0.70 (0.60–0.82)	<60 (n = 792)	0.68 (0.56–0.84)	N/A
RALES [37, 38]	Spironolactone versus placebo (n = 1663)	LVEF <35%; NYHA III–IV; creatinine ≤221 μmol/L	2	All-cause mortality	0.70 (0.60–0.82)	≥60 (n = 866)	0.71 (0.57–0.90)	N/A
EMPHASIS-HF [39]	Eplerenone versus placebo (n = 2737)	LVEF ≤35%; NYHA II; eGFR ≥30 mL/min/1.73 m²	1.75	CV death or hospitalization for HF	0.63 (0.54–0.74)	<60 (n = 912)	N/A	0.50
EMPHASIS-HF [39]	Eplerenone versus placebo (n = 2737)	LVEF ≤35%; NYHA II; eGFR ≥30 mL/min/1.73 m²	1.75	CV death or hospitalization for HF	0.63 (0.54–0.74)	≥60 (n = 1821)	N/A	0.50

Angiotensin receptor neprilysin inhibitor
PARADIGM-HF [40]	Sacubitril/valsartan versus enalapril (n = 8442)	LVEF ≤40%; NYHA II–IV; eGFR ≥30 mL/min/1.73 m²	2.25	CV death or hospitalization for HF	0.80 (0.73–0.87)	<60 (n = 3061)	N/A	0.91
PARADIGM-HF [40]	Sacubitril/valsartan versus enalapril (n = 8442)	LVEF ≤40%; NYHA II–IV; eGFR ≥30 mL/min/1.73 m²	2.25	CV death or hospitalization for HF	0.80 (0.73–0.87)	≥60 (n = 5338)	N/A	0.91

ICD
MADIT II [41]	Prophylactic ICD versus conventional medical therapy (n = 1232)	LVEF ≤30%; NYHA III; eGFR ≥15 mL/min/1.73 m²	2.67	All-cause mortality	0.69 (0.51–0.93)	<35 (n = 80)	1.09 (0.49–2.43)	0.29
						35–59 (n = 387)	0.74 (0.48–1.15)
						≥60 (n = 756)	0.66 (0.43–1.02)

CRT
CARE-HF [42]	CRT versus conventional medical therapy (n = 813)	LVEF ≤35%; NYHA III–IV;	1.5	Death from any cause or unplanned hospitalization for a major CV event	0.63 (0.51–0.77)	<60 (n = 369)	0.67 (0.50–0.89)	N/A
CARE-HF [42]	CRT versus conventional medical therapy (n = 813)	LVEF ≤35%; NYHA III–IV;	1.5		0.63 (0.51–0.77)	≥60 (n = 370)	0.57 (0.40–0.80)	N/A

Data extracted from large trials where subgroup analysis by kidney function is available. NYHA, New York Heart Association; CV, cardiovascular; N/A, not available.