Subgroup Placebo n/N (K-M%) Serelaxin n/N (K-M%) Favours serelaxin Favours placebo Hazard ratio Estimate (95%CI) Interaction P value Total population 65/580.

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Subgroup Placebo n/N (K-M%) Serelaxin n/N (K-M%) Favours serelaxin Favours placebo Hazard ratio Estimate (95%CI) Interaction P value Total population 65/580 (11.3)42/581 (7.3)0.63 (0.43, 0.93) Gender Male40/357 (11.3)28/368 (7.7) 0.67 (0.41, 1.08) Female25/223 (11.3)14/213 (6.7) 0.58 (0.30, 1.11) Age <65 years9/119 (7.6)11/145 (7.8) 1.01 (0.42, 2.43) ≥65 years56/461 (12.3)31/436 (7.2) 0.57 (0.37, 0.89) <75 years23/296 (7.8)24/315 (7.8) 0.98 (0.56, 1.74) ≥75 years42/284 (15.0)18/266 (6.8) 0.44 (0.25, 0.76) Region Eastern Europe35/282 (12.5)23/280 (8.3) 0.65 (0.38, 1.10) Western Europe9/101 (9.1)4/103 (4.2) 0.42 (0.13, 1.36) South America4/37 (10.9)4/34 (11.8) 1.09 (0.27, 4.37) North America5/55 (9.1)6/59 (10.2) 1.09 (0.33, 3.59) Israel12/105 (11.4)5/105 (4.8) 0.42 (0.15, 1.18) Race White / Caucasian62/552 (11.3)38/544 (7.1) 0.61 (0.41, 0.92) Other3/28 (10.7)4/37 (11.5) 0.94 (0.21, 4.21) Hosp. for CHF in past year Yes18/181 (9.9)23/216 (10.9) 1.10 (0.59, 2.04) No47/399 (11.9)19/365 (5.3) 0.42 (0.25, 0.72) SBP <140 mmHg38/284 (13.5)26/298 (8.9) 0.64 (0.39, 1.05) ≥140 mmHg27/294 (9.2)15/279 (5.5) 0.58 (0.31, 1.09) Heart rate <80 bpm32/296 (10.8)19/314 (6.1) 0.55 (0.31, 0.97) ≥80 bpm33/284 (11.8)23/267 (8.8) 0.73 (0.43, 1.24) LVEF <40%30/295 (10.2)24/303 (8.0) 0.77 (0.45, 1.32) ≥40%30/244 (12.4)16/249 (6.5) 0.51 (0.28, 0.94) History of IHD Yes38/307 (12.5)21/296 (7.1) 0.56 (0.33, 0.95) No27/273 (10.0)21/285 (7.5) 0.74 (0.42, 1.31) History of ICD or CRT Yes18/141 (12.9)17/153 (11.3) 0.87 (0.45, 1.69) No47/439 (10.8)25/428 (5.9) 0.53 (0.33, 0.87) History of DM Yes32/272 (11.8)21/279 (7.6) 0.63 (0.36, 1.10) No33/308 (10.8)21/302 (7.1) 0.64 (0.37, 1.10) History of AF Yes41/305 (13.6)23/297 (7.8) 0.56 (0.34, 0.94) No24/275 (8.8)19/284 (6.8) 0.76 (0.42, 1.39) AF at screening Yes36/246 (14.8)15/233 (6.5) 0.42 (0.23, 0.76) No29/333 (8.8)27/347 (7.9) 0.90 (0.53, 1.52) Time from present. to rand. <6 h27/266 (10.2)25/275 (9.2) 0.90 (0.52, 1.55) ≥6 h38/314 (12.2)17/306 (5.6) 0.44 (0.25, 0.79) ACEI/ARB use at baseline Yes38/398 (9.6)26/390 (6.8) 0.70 (0.42, 1.15) No27/182 (15.1)16/191 (8.5) 0.54 (0.29, 1.00) Beta-blocker use at baseline Yes43/407 (10.7)29/387 (7.6) 0.70 (0.44, 1.12) No22/173 (12.7)13/194 (6.8) 0.51 (0.26, 1.01) MRA use at baseline Yes20/173 (11.7)20/192 (10.6) 0.91 (0.49, 1.70) No45/407 (11.1)22/389 (5.7) 0.50 (0.30, 0.82) IV nitrates at baseline Yes7/42 (17.0)5/39 (12.8) 0.73 (0.23, 2.31) No58/538 (10.9)37/542 (6.9) 0.62 (0.41, 0.94) Lymphocytes at baseline ≤12%29/127 (23.2)9/110 (8.3) 0.32 (0.15, 0.69) >12%33/409 (8.1)30/425 (7.2) 0.88 (0.53, 1.44) Troponin T at baseline ≤0.024 μg/L 10/165 (6.1)6/176 (3.4) 0.56 (0.20, 1.54) –0.045 μg/L 14/196 (7.2)14/182 (7.7) 1.08 (0.52, 2.27) >0.045 μg/L 32/180 (18.0)17/175 (10.0) 0.51 (0.28, 0.92) NT-proBNP at baseline <5000 ng/L18/279 (6.5)16/288 (5.6) 0.86 (0.44, 1.69) ≥5000 ng/L41/272 (15.3)24/262 (9.3) 0.58 (0.35, 0.97) ≤3346 ng/L 9/190 (4.7)5/177 (2.8) 0.59 (0.20, 1.76) –7281 ng/L 20/174 (11.6)18/194 (9.4) 0.81 (0.43, 1.53) >7281 ng/L 30/187 (16.4)17/179 (9.6) 0.56 (0.31, 1.02) Cystatin C at baseline ≤1.26 mg/L 8/180 (4.5)11/189 (5.9) 1.33 (0.53, 3.30) –1.65 mg/L 22/191 (11.7)8/180 (4.5) 0.37 (0.17, 0.83) >1.65 mg/L 29/180 (16.2)21/181 (11.7) 0.70 (0.40, 1.23) eGFR at baseline <60 ml/min/1.73m 2 55/408 (13.6)30/409 (7.4) 0.53 (0.34, 0.83) ≥60 ml/min/1.73m 2 8/160 (5.0)10/155 (6.6) 1.30 (0.51, 3.29) <50 ml/min/1.73m 2 46/272 (17.1)21/268 (7.9) 0.44 (0.26, 0.74) ≥50 ml/min/1.73m 2 17/296 (5.8)19/296 (6.5) 1.13 (0.59, 2.17) Hazard ratio (95% CI) for all-cause mortality through Day 180