Subgroup  

Placebon/N (%)

Serelaxinn/N (%)

Favours placebo Favours serelaxin

Odds ratioEstimate (95%CI)

InteractionP value

Total population 150/580 (25.9) 156/581 (26.9) 1.05 (0.81, 1.37)Gender Male 85/357 (23.8) 85/368 (23.1)     0.96 (0.68, 1.36) 0.3867

Female 65/223 (29.2) 71/213 (33.3)     1.22 (0.81, 1.82)  

Age <65 years 32/119 (26.9) 50/145 (34.5)     1.43 (0.84, 2.43) 0.1706

≥65 years 118/461 (25.6) 106/436 (24.3)     0.93 (0.69, 1.26)

<75 years 78/296 (26.4) 93/315 (29.5)     1.17 (0.82, 1.67) 0.3559

≥75 years 72/284 (25.4) 63/266 (23.7)     0.91 (0.62, 1.35)   

Region Eastern Europe 89/282 (31.6) 87/280 (31.1)     0.98 (0.68, 1.40) 0.9358

Western Europe 17/101 (16.8) 20/103 (19.4)     1.19 (0.58, 2.43)  

South America 18/37 (48.7) 16/34 (47.1)     0.94 (0.37, 2.38)  

North America 20/55 (36.4) 25/59 (42.4)     1.29 (0.61, 2.73)  

Israel 6/105 (5.7) 8/105 (7.6)     1.36 (0.46, 4.07)  

Race White / Caucasian 142/552 (25.7) 139/544 (25.6)     0.99 (0.76, 1.30) 0.1656

Other 8/28 (28.6) 17/37 (50.0)     2.13 (0.75, 6.04)  

Hosp. for CHF in past yearP

Yes 43/181 (23.8) 56/216 (25.9)     1.12 (0.71, 1.78) 0.7604

No 107/399 (26.8) 100/365 (27.4)     1.03 (0.75, 1.42)  

SBP <140 mmHg 66/284 (23.2) 68/298 (22.8)     0.98 (0.66, 1.44) 0.4985

≥140 mmHg 83/294 (28.2) 88/279 (31.5)     1.17 (0.82, 1.68)  

Heart rateP <80 bpm 78/296 (26.4) 72/314 (22.9)     0.83 (0.58, 1.20) 0.0691

≥80 bpm 72/284 (25.4) 84/267 (31.5)     1.35 (0.93, 1.96)  

LVEF 

<40% 79/295 (26.8) 76/303 (25.1)     0.92 (0.63, 1.32) 0.4556 ≥40% 62/244 (25.4) 69/249 (27.7)     1.13 (0.75, 1.68)

History of IHD Yes 69/307 (22.5) 64/296 (21.6)     0.95 (0.65, 1.40) 0.5226

No 81/273 (29.7) 92/285 (32.3)     1.13 (0.79, 1.62)  

History of ICD or CRT

Yes 27/141 (19.2) 35/153 (22.9)     1.25 (0.71, 2.20) 0.5142

No 123/439 (28.0) 121/428 (28.3)     1.01 (0.75, 1.36)  

History of DM Yes 63/272 (23.2) 76/279 (27.2)     1.24 (0.84, 1.83) 0.2547

No 87/308 (28.3) 80/302 (26.5)     0.92 (0.64, 1.31)  

History of AF Yes 69/305 (22.6) 74/297 (24.9)     1.13 (0.78, 1.65) 0.5625

No 81/275 (29.5) 82/284 (28.9)     0.97 (0.68, 1.40)  

AF at screening Yes 55/246 (22.4) 55/233 (23.6)     1.07 (0.70, 1.64) 0.8382

No 95/333 (28.5) 100/347 (28.8)      1.01 (0.73, 1.41)  

Time frompresent. to rand.

<6 h 58/266 (21.8) 65/275 (23.6)     1.11 (0.74, 1.66) 0.7585

≥6 h 92/314 (29.3) 91/306 (29.7)     1.02 (0.72, 1.44)  

ACEI/ARB use at baselineP

Yes 103/398 (25.9) 97/390 (24.9)     0.95 (0.69, 1.31) 0.2840

No 47/182 (25.8) 59/191 (30.9)     1.28 (0.82, 2.02)  

Beta-blocker use at baselineP

Yes 89/407 (21.9) 96/387 (24.8)     1.18 (0.85, 1.64) 0.1959

No 61/173 (35.3) 60/194 (30.9)     0.82 (0.53, 1.27)  

MRA use at baselineP

Yes 43/173 (24.9) 48/192 (25.0)     1.01 (0.63, 1.62) 0.8174

No 107/407 (26.3) 108/389 (27.8)     1.08 (0.79, 1.47)  

IV nitrates at baseline

Yes 14/42 (33.3) 16/39 (41.0)     1.39 (0.56, 3.44) 0.5315

No 136/538 (25.3) 140/542 (25.8)     1.03 (0.78, 1.35)  

Lymphocytes at baselineP

≤12% 32/127 (25.2) 24/110 (21.8)     0.83 (0.45, 1.52) 0.5269

>12% 113/409 (27.6) 120/425 (28.2)     1.03 (0.76, 1.39)  

Troponin T at baselineM

≤0.024 μg/L 44/165 (26.7) 42/176 (23.9)     0.86 (0.53, 1.41) 0.8953

0.025–0.045 μg/L 53/196 (27.0) 47/182 (25.8)     0.94 (0.59, 1.48)  

>0.045 μg/L 52/180 (28.9) 51/175 (29.1)     1.01 (0.64, 1.60)  

NT-proBNP at baseline

<5000 ng/L 73/279 (26.2) 74/288 (25.7)     0.98 (0.67, 1.42) 0.7799

≥5000 ng/L 76/272 (27.9) 68/262 (26.0)     0.90 (0.62, 1.33)  

≤3346 ng/L 50/190 (26.3) 48/177 (27.1)     1.04 (0.66, 1.65) 0.4540

3347–7281 ng/L 43/174 (24.7) 51/194 (26.3)     1.09 (0.68, 1.74)  

>7281 ng/L 56/187 (30.0) 43/179 (24.0)     0.74 (0.46, 1.18)  

Cystatin C at baseline

≤1.26 mg/L 47/180 (26.1) 50/189 (26.5)     1.02 (0.64, 1.62) 0.9215

1.27–1.65 mg/L 57/191 (29.8) 50/180 (27.8)     0.90 (0.58, 1.42)  

>1.65 mg/L 45/180 (25.0) 42/181 (23.2)     0.91 (0.56, 1.47)  

eGFR at baseline

<60 ml/min/1.73m2 104/408 (25.5) 113/409 (27.6)     1.12 (0.82, 1.52) 0.3844

≥60 ml/min/1.73m2 45/160 (28.1) 39/155 (25.2)     0.86 (0.52, 1.42)  

<50 ml/min/1.73m2 74/272 (27.2) 72/268 (26.9)     0.98 (0.67, 1.44) 0.6976

≥50 ml/min/1.73m2 75/296 (25.3) 80/296 (27.0)     1.09 (0.76, 1.57)  

Odds ratio (95%CI) for moderate or marked improvement in dyspnoea at 6,12 and 24 hours (Likert)

0.1 1 10

Abbreviations for the figure legendACEI = angiotensin converting enzyme inhibitor; AF = atrial fibrillation; ARB = angiotensin receptor blocker; bpm = beats per minute; CRT = cardiac resynchronization therapy; DM = diabetes mellitus; eGFR = estimated glomerular filtration rate; h = hours; hosp. = hospitalization; ICD = implantable cardioverter defibrillator; IHD = ischemic heart disease; IV = intravenous; LVEF = left ventricular ejection fraction; NT-proBNP = N-terminal prohormone B-type natriuretic peptide; MRA = mineralocorticoid receptor antagonist; present. = presentation; rand. = randomization; SBP = systolic blood pressure