Introduction
Methods
Statistical analyses
Results
Japan | Non-Japan | |||
---|---|---|---|---|
Empagliflozin (N = 304) | Placebo (N = 308) | Empagliflozin (N = 3000) | Placebo (N = 2997) | |
DEMOGRAPHICS | ||||
Age (years) | 64.4 (12.2) | 66.2 (11.8) | 63.8 (14.0) | 63.5 (14.0) |
Female sex | 86 (28.3) | 75 (24.4) | 1011 (33.7) | 1020 (34.0) |
Race | ||||
White | 0 (0.0) | 0 (0.0) | 1939 (64.6) | 1920 (64.1) |
Black | 0 (0.0) | 0 (0.0) | 128 (4.3) | 134 (4.5) |
Asian | 304 (100.0) | 308 (100.0) | 890 (29.7) | 891 (29.7) |
Mixed | 0 (0.0) | 0 (0.0) | 14 (0.5) | 7 (0.2) |
Other | 0 (0.0) | 0 (0.0) | 29 (1.0) | 45 (1.5) |
PRIOR DISEASE | ||||
Diabetes | ||||
Yes | 135 (44.4) | 155 (50.3) | 1390 (46.3) | 1360 (45.4) |
No | 169 (55.6) | 153 (49.7) | 1610 (53.7) | 1637 (54.6) |
Diabetes type | ||||
Type 1 | 0 (0.0) | 0 (0.0) | 34 (1.1) | 34 (1.1) |
Type 2 | 127 (41.8) | 148 (48.1) | 1343 (44.8) | 1318 (44.0) |
Other/unknown | 8 (2.6) | 7 (2.3) | 13 (0.4) | 8 (0.3) |
Cardiovascular disease | ||||
Yes | 40 (13.2) | 50 (16.2) | 821 (27.4) | 854 (28.5) |
No | 264 (86.8) | 258 (83.8) | 2179 (72.6) | 2143 (71.5) |
Primary kidney diagnosis | ||||
Diabetic kidney disease | 94 (30.9) | 109 (35.4) | 938 (31.3) | 916 (30.6) |
Hypertension/renovascular | 41 (13.5) | 45 (14.6) | 665 (22.2) | 694 (23.2) |
Glomerular | 102 (33.6) | 93 (30.2) | 751 (25.0) | 723 (24.1) |
Other/unknown | 67 (22.0) | 61 (19.8) | 646 (21.5) | 664 (22.2) |
CLINICAL MEASUREMENTS | ||||
Blood pressure (mmHg) | ||||
Systolic | 133.9 (16.2) | 135.9 (17.3) | 136.6 (18.3) | 136.7 (18.5) |
Diastolic | 77.4 (11.6) | 78.5 (12.5) | 78.1 (11.7) | 78.0 (11.9) |
Body mass index (kg/m2) | 25.1 (4.1) | 25.3 (4.0) | 30.2 (6.7) | 30.3 (6.9) |
LABORATORY MEASUREMENTS | ||||
Estimated GFR (mL/min/1.73m2) | ||||
Mean (SD) | 46.2 (17.9) | 44.3 (18.4) | 36.5 (13.8) | 36.5 (13.7) |
Distribution | ||||
30 | 62 (20.4) | 72 (23.4) | 1069 (35.6) | 1079 (36.0) |
≥30 < 45 | 102 (33.6) | 115 (37.3) | 1365 (45.5) | 1346 (44.9) |
≥45 | 140 (46.1) | 121 (39.3) | 566 (18.9) | 572 (19.1) |
Urinary albumin-to-creatinine ratio (mg/g) | ||||
Geometric mean (95% CI) | 566 (484–661) | 593 (508–693) | 199 (185–213) | 204 (190–220) |
Median (Q1–Q3) | 719 (293–1394) | 602 (293–1727) | 292 (39–1009) | 288 (41–1041) |
Distribution | ||||
30 | 16 (5.3) | 11 (3.6) | 649 (21.6) | 652 (21.8) |
≥30 < 300 | 61 (20.1) | 71 (23.1) | 866 (28.9) | 866 (28.9) |
≥300 | 227 (74.7) | 226 (73.4) | 1485 (49.5) | 1479 (49.3) |
NT-proBNP (ng/L) | 88 (40–208) | 103 (45–215) | 174 (76–442) | 165 (72–437) |
MEDICATIONS | ||||
RAS inhibitor | 261 (85.9) | 271 (88.0) | 2570 (85.7) | 2526 (84.3) |
Any diuretic therapy | 61 (20.1) | 64 (20.8) | 1301 (43.4) | 1389 (46.3) |
Any lipid-lowering therapy | 182 (59.9) | 193 (62.7) | 2008 (66.9) | 1995 (66.6) |
Japan | Non-Japan | Overall | ||||||
---|---|---|---|---|---|---|---|---|
Empagliflozin (N = 304) | Placebo (N = 308) | Empagliflozin (N = 3000) | Placebo (N = 2997) | Empagliflozin (N = 3304) | Placebo (N = 3305) | Overall HR (95% CI) | Japan vs. non-Japan Phet | |
n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | |||
Primary outcome: progression of kidney disease or death from cardiovascular causes | 33 (10.9) | 64 (20.8) | 399 (13.3) | 494 (16.5) | 432 (13.1) | 558 (16.9) | 0.72 (0.64–0.82) | 0.06 |
Key secondary outcomesa | ||||||||
Hospitalization for heart failure or death from cardiovascular causes | 6 (2.0) | 11 (3.6) | 125 (4.2) | 141 (4.7) | 131 (4.0) | 152 (4.6) | 0.84 (0.67–1.07) | 0.56 |
Death from any cause | 7 (2.3) | 7 (2.3) | 141 (4.7) | 160 (5.3) | 148 (4.5) | 167 (5.1) | 0.87 (0.70–1.08) | 0.52 |
Other secondary outcomes | ||||||||
Progression of kidney disease | 31 (10.2) | 63 (20.5) | 353 (11.8) | 441 (14.7) | 384 (11.6) | 504 (15.2) | 0.71 (0.62–0.81) | 0.04 |
Death from cardiovascular causes | 3 (1.0) | 1 (0.3) | 56 (1.9) | 68 (2.3) | 59 (1.8) | 69 (2.1) | 0.84 (0.60–1.19) | – |
End-stage kidney disease or death from cardiovascular causesb | 10 (3.3) | 16 (5.2) | 153 (5.1) | 201 (6.7) | 163 (4.9) | 217 (6.6) | 0.73 (0.59–0.89) | 0.88 |
Safety outcomes | ||||||||
Serious urinary tract infection | 1 (0.3) | 2 (0.6) | 51 (1.7) | 52 (1.7) | 52 (1.6) | 54 (1.6) | 0.94 (0.64–1.37) | 0.67 |
Serious genital infection | 0 (0.0) | 0 (0.0) | 1 (< 0.1) | 1 (< 0.1) | 1 (< 0.1) | 1 (< 0.1) | – | – |
Serious hyperkalemia | 1 (0.3) | 2 (0.6) | 91 (3.0) | 107 (3.6) | 92 (2.8) | 109 (3.3) | 0.83 (0.63–1.09) | 0.76 |
Serious acute kidney injury | 1 (0.3) | 4 (1.3) | 106 (3.5) | 131 (4.4) | 107 (3.2) | 135 (4.1) | 0.78 (0.60–1.00) | 0.35 |
Serious dehydration | 2 (0.7) | 3 (1.0) | 28 (0.9) | 21 (0.7) | 30 (0.9) | 24 (0.7) | 1.25 (0.73–2.14) | 0.62 |
Liver injury | 2 (0.7) | 0 (0.0) | 11 (0.4) | 12 (0.4) | 13 (0.4) | 12 (0.4) | 1.09 (0.50–2.38) | 0.99 |
Ketoacidosisc | 0 (0.0) | 0 (0.0) | 6 (0.2) | 1 (< 0.1) | 6 (0.2) | 1 (< 0.1) | – | – |
Lower-limb amputation | 2 (0.7) | 0 (0.0) | 26 (0.9) | 19 (0.6) | 28 (0.8) | 19 (0.6) | 1.43 (0.80–2.57) | 0.98 |
Bone fracture | 17 (5.6) | 14 (4.5) | 116 (3.9) | 109 (3.6) | 133 (4.0) | 123 (3.7) | 1.08 (0.84–1.38) | 0.66 |
Severe hypoglycemiad | 10 (3.3) | 6 (1.9) | 67 (2.2) | 71 (2.4) | 77 (2.3) | 77 (2.3) | 1.00 (0.73–1.37) | 0.21 |
Symptomatic dehydratione | 6 (2.0) | 6 (1.9) | 77 (2.6) | 70 (2.3) | 83 (2.5) | 76 (2.3) | 1.10 (0.81–1.51) | 0.96 |