Background
Methods
Data source and patients
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Baseline ESA nonusers: as of index date (01 April 2011), had been enrolled with the provider for ≥8 weeks without use of ESA during this period.
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Baseline ESA users: as of index date (01 April 2011), were enrolled with the provider and had received ESA within the prior 6 weeks, and did not have Hb >12.5 g/dL (to exclude potential influence of patients who were being treated off label).
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ESA naives: between 01 April 2011 and 30 June 2013 had been enrolled in with the provider for ≥90 days without ESA treatment and subsequently received ESA (index date). It is important to note that ESA naives may have been included in other groups at baseline. However, in describing the source population, such patients were not double counted.
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≤10 versus >10 g/dL for baseline non-users and ESA naives in whom the implied decision is whether to initiate ESA.
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≤11 versus >11 g/dL among baseline ESA users in whom the implied decision is to continue or discontinue ESA.
Outcomes
Analytic methods
Ethics and compliance
Results
Baseline patient characteristics
Baseline ESA Nonusers | Baseline ESA Users | ESA Naives | Source population | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Hb 8–10 g/dL (N = 761) | Hb 10.1–10.5 g/dL (N = 780) | Hb >10.5 g/dL (N = 30,658) | All (N = 32,199) | Hb 8–11 g/dL (N = 79) | Hb 11.1–12.5 g/dL (N = 30) | All (N = 109) | Hb 8–10 g/dL (N = 193) | Hb >10 g/dL (N = 73) | All (N = 266) | All (N = 35,509) | |
Age (years) mean ± SD | 78.6 ± 11.5 | 78.4 ± 11.3 | 76.1 ± 10.8 | 76.2 ± 10.8 | 78.1 ± 12.5 | 81.2 ± 7.9 | 78.9 ± 11.5 | 78.0 ± 10.7 | 79.1 ± 11.3 | 78.3 ± 10.9 | 76.1 ± 10.8 |
Sex, n (%) | |||||||||||
Male | 228 (30.0) | 220 (28.2) | 11,638 (38.0) | 12,086 (37.6) | 31 (39.2) | 9 (30.0) | 40 (36.7) | 79 (40.9) | 23 (31.5) | 102 (38.4) | 13,456 (37.9) |
Female | 533 (70.0) | 560 (71.8) | 19,020 (62.0) | 20,113 (62.5) | 48 (60.8) | 21 (70.0) | 69 (63.3) | 114 (59.1) | 50 (68.5) | 164 (61.7) | 22,053 (62.1) |
Race/ethnicity, n (%) | |||||||||||
White | 150 (19.7) | 188 (24.1) | 8821 (28.8) | 9159 (28.4) | 11 (13.9) | 3 (10.0) | 14 (12.8) | 33 (17.1) | 15 (20.6) | 48 (18.1) | 10,045 (28.3) |
Black | 58 (7.6) | 53 (6.8) | 1616 (5.3) | 1727 (5.4) | 9 (11.4) | 0 | 9 (8.3) | 16 (8.3) | 6 (8.2) | 22 (8.3) | 1912 (5.4) |
Hispanic | 91 (12.0) | 69 (8.9) | 2108 (6.9) | 2268 (7.0) | 8 (10.1) | 2 (6.7) | 10 (9.2) | 20 (10.4) | 7 (9.6) | 27 (10.2) | 2425 (6.8) |
Asian | 26 (3.4) | 30 (3.9) | 1221 (4.0) | 1277 (4.0) | 11 (13.9) | 1 (3.3) | 12 (11.0) | 13 (6.7) | 5 (6.9) | 18 (6.8) | 1410 (4.0) |
CKD stage, n (%) | |||||||||||
3A | 322 (42.3) | 318 (40.8) | 21,869 (71.3) | 22,509 (69.9) | 8 (10.1) | 6 (20.0) | 14 (12.8) | 19 (9.8) | 6 (8.2) | 25 (9.4) | 24,723 (69.6) |
3B | 267 (35.1) | 310 (39.7) | 7389 (24.1) | 7966 (24.7) | 19 (24.1) | 12 (40.0) | 31 (28.4) | 50 (25.9) | 28 (38.4) | 78 (29.3) | 8829 (24.9) |
4 | 151 (19.8) | 141 (18.1) | 1343 (4.4) | 1635 (5.1) | 44 (55.7) | 11 (36.7) | 55 (50.5) | 100 (51.8) | 33 (45.2) | 133 (50.0) | 1849 (5.2) |
5 | 21 (2.8) | 11 (1.4) | 57 (0.2) | 89 (0.3) | 8 (10.1) | 1 (3.3) | 9 (8.3) | 24 (12.4) | 6 (8.2) | 30 (11.3) | 108 (0.3) |
Diabetes, n (%) | 449 (59.0) | 466 (59.7) | 12,850 (41.9) | 13,765 (42.8) | 55 (69.6) | 20 (66.7) | 75 (68.8) | 128 (66.3) | 45 (61.6) | 173 (65.0) | 15,282 (43.0) |
Hypertension, n (%) | 703 (92.4) | 716 (91.8) | 26,331 (85.9) | 27,750 (86.2) | 77 (97.5) | 29 (96.7) | 106 (97.3) | 188 (97.4) | 71 (97.3) | 259 (97.4) | 30,654 (86.3) |
CHF, n (%) | 312 (41.0) | 264 (33.9) | 6641 (21.7) | 7217 (22.4) | 40 (50.6) | 10 (33.3) | 50 (45.9) | 97 (50.3) | 38 (52.1) | 135 (50.8) | 7813 (22.0) |
MI, n (%) | 148 (19.5) | 141 (18.1) | 4428 (14.4) | 4717 (14.7) | 19 (24.1) | 6 (20.0) | 25 (22.9) | 47 (24.4) | 20 (27.4) | 67 (25.2) | 5182 (14.6) |
Stroke, n (%) | 141 (18.5) | 136 (17.4) | 4175 (13.6) | 4452 (13.8) | 14 (17.7) | 7 (23.3) | 21 (19.3) | 49 (25.4) | 15 (20.6) | 64 (24.1) | 4855 (13.7) |
PVD, n (%) | 282 (37.1) | 269 (34.5) | 7599 (24.8) | 8150 (25.3) | 33 (41.8) | 12 (40.0) | 45 (41.3) | 92 (47.7) | 28 (38.4) | 120 (45.1) | 8805 (24.8) |
Albuminuria, n (%) | |||||||||||
<300 mg/dL | 273 (35.9) | 288 (36.9) | 11,084 (36.2) | 11,645 (36.2) | 26 (32.9) | 11 (36.7) | 37 (33.9) | 56 (29.0) | 26 (35.6) | 82 (30.8) | 12,459 (35.1) |
≥300 mg/dL | 109 (14.3) | 100 (12.8) | 1575 (5.1) | 1784 (5.5) | 23 (29.1) | 2 (6.7) | 25 (22.9) | 69 (35.8) | 15 (20.6) | 84 (31.6) | 1917 (5.4) |
Not available | 379 (49.8) | 392 (50.2) | 17,999 (58.7) | 18,770 (58.3) | 30 (38.0) | 17 (56.7) | 47 (43.1) | 68 (35.2) | 32 (43.8) | 100 (37.6) | 21,133 (59.5) |
eGFR, mL/min/1.73m2, mean ± SD | 40.3 ± 12.6 | 40.5 ± 11.8 | 48.3 ± 9.1 | 47.9 ± 9.4 | 27.0 ± 11.6 | 32.8 ± 12.0 | 28.6 ± 11.9 | 26.9 ± 11.6 | 29.5 ± 11.5 | 27.6 ± 11.6 | 47.8 ± 9.5 |
Hb, g/dL, mean ± SD | 9.5 ± 0.5 | 10.3 ± 0.1 | 13.3 ± 1.4 | 13.2 ± 1.6 | 9.9 ± 0.7 | 11.6 ± 0.4 | 10.4 ± 1.0 | 9.2 ± 0.5 | 11.1 ± 1.4 | 9.7 ± 1.2 | 13.1 ± 1.6 |
Ferritin, ng/mL, p50 [p25, p75] | 119 [40, 276] | 96 [45, 185] | 97 [48, 192] | 98 [47, 197] | 242 [138, 483] | 243 [141, 319] | 242 [138, 453] | 242 [106, 415] | 200 [96, 428] | 224 [104, 418] | 99 [48, 201] |
TSAT, %, mean ± SD | 22.7 ± 14.4 | 22.8 ± 11.5 | 26.0 ± 10.8 | 25.5 ± 11.3 | 28.7 ± 13.5 | 30.3 ± 15.1 | 29.0 ± 13.6 | 25.6 ± 12.2 | 29.8 ± 14.1 | 26.6 ± 12.7 | 25.6 ± 11.4 |
Longitudinal trends of anemia and anemia treatment in CKD patients
Rates of cardiovascular events and death
Baseline ESA Nonusers | Baseline ESA Users | ESA Naives | ||||||||
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Hb 8–10 g/dL | Hb 10.1–10.5 g/dL | Hb >10.5 g/dL | All | Hb 8–11 g/dL | Hb 11.1–12.5 g/dL | All | Hb 8–10 g/dL | Hb >10 g/dL | All | |
(N = 761) | (N = 780) | (N = 30,658) | (N = 32,199) | (N = 79) | (N = 30) | (N = 109) | (N = 193) | (N = 73) | (N = 266) | |
eGFR, mL/min/1.73m2, mean ± SD | 40.3 ± 12.6 | 40.5 ± 11.8 | 48.3 ± 9.1 | 47.9 ± 9.4 | 27.0 ± 11.6 | 32.8 ± 12.0 | 28.6 ± 11.9 | 26.9 ± 11.6 | 29.5 ± 11.5 | 27.6 ± 11.6 |
MACE | ||||||||||
Event n | 283 | 226 | 5788 | 6297 | 28 | 8 | 36 | 55 | 22 | 77 |
Pt-year | 1345 | 1552 | 68,321 | 71,218 | 125 | 59 | 183 | 209 | 89 | 298 |
Mean follow-up, years | 1.77 | 1.99 | 2.23 | 2.21 | 1.58 | 1.95 | 1.68 | 1.08 | 1.22 | 1.12 |
Rate per 100 pt-year (95% CI) | 21.04 (18.73, 23.64) | 14.56 (12.78, 16.59) | 8.47 (8.26, 8.69) | 8.84 (8.63, 9.06) | 22.45 (15.50, 32.51) | 13.66 (6.83, 27.31) | 19.64 (14.17, 27.23) | 26.32 (20.20, 34.28) | 24.67 (16.24, 37.46) | 25.82 (20.65, 32.28) |
MACE+ | ||||||||||
Event n | 369 | 301 | 7515 | 8185 | 40 | 15 | 55 | 80 | 32 | 112 |
Pt-year | 1203 | 1428 | 65,674 | 68,305 | 106 | 48 | 154 | 178 | 78 | 257 |
Mean follow-up, years | 1.58 | 1.83 | 2.14 | 2.12 | 1.34 | 1.61 | 1.42 | 0.92 | 1.07 | 0.97 |
Rate per 100 pt-year (95% CI) | 30.66 (27.69, 33.95) | 21.08 (18.83, 23.60) | 11.44 (11.19, 11.70) | 11.98 (11.73, 12.25) | 37.78 (27.71, 51.51) | 30.98 (18.68, 51.38) | 35.65 (27.37, 46.43) | 44.84 (36.02, 55.83) | 40.85 (28.89, 57.77) | 43.62 (36.25, 52.50) |
Death | ||||||||||
Event n | 190 | 136 | 2573 | 2899 | 20 | 6 | 26 | 32 | 10 | 42 |
Pt-year | 1533 | 1734 | 73,529 | 76,796 | 142 | 61 | 202 | 235 | 102 | 337 |
Mean follow-up, years | 2.01 | 2.22 | 2.40 | 2.39 | 1.79 | 2.03 | 1.86 | 1.22 | 1.40 | 1.27 |
Rate per 100 pt-year (95% CI) | 12.39 (10.75, 14.28) | 7.84 (6.63, 9.28) | 3.50 (3.37, 3.64) | 3.77 (3.64, 3.91) | 14.12 (9.11, 21.88) | 9.87 (4.43, 21.97) | 12.84 (8.74, 18.86) | 13.63 (9.64, 19.27) | 9.82 (5.28, 18.24) | 12.48 (9.22, 16.88) |
MI | ||||||||||
Event n | 109 | 107 | 2587 | 2803 | 15 | 2 | 17 | 32 | 7 | 39 |
Pt-year | 1441 | 1629 | 70,796 | 73,866 | 128 | 59 | 187 | 216 | 96 | 312 |
Mean follow-up, years | 1.89 | 2.09 | 2.31 | 2.29 | 1.62 | 1.96 | 1.71 | 1.12 | 1.31 | 1.17 |
Rate per 100 pt-year (95% CI) | 7.57 (6.27, 9.13) | 6.57 (5.43, 7.94) | 3.65 (3.52, 3.80) | 3.79 (3.66, 3.94) | 11.72 (7.06, 19.44) | 3.41 (0.85, 13.63) | 9.11 (5.66, 14.65) | 14.78 (10.45, 20.90) | 7.31 (3.48, 15.33) | 12.49 (9.13, 17.09) |
Stroke | ||||||||||
Event n | 123 | 90 | 2840 | 3053 | 5 | 2 | 7 | 16 | 11 | 27 |
Pt-year | 1409 | 1632 | 70,395 | 73,436 | 138 | 61 | 199 | 224 | 94 | 319 |
Mean follow-up, years | 1.85 | 2.09 | 2.30 | 2.28 | 1.75 | 2.02 | 1.82 | 1.16 | 1.29 | 1.20 |
Rate per 100 pt-year (95% CI) | 8.73 (7.32, 10.42) | 5.51 (4.49, 6.78) | 4.03 (3.89, 4.19) | 4.16 (4.01, 4.31) | 3.62 (1.51, 8.70) | 3.29 (0.82, 13.17) | 3.52 (1.68, 7.38) | 7.14 (4.37, 11.65) | 11.65 (6.45, 21.03) | 8.47 (5.81, 12.36) |
CHF hospitalization | ||||||||||
Event n | 261 | 224 | 4443 | 4928 | 31 | 14 | 45 | 66 | 23 | 89 |
Pt-year | 1291 | 1497 | 68,827 | 71,614 | 112 | 48 | 161 | 188 | 84 | 272 |
Mean follow-up, years | 1.70 | 1.92 | 2.24 | 2.22 | 1.42 | 1.62 | 1.47 | 0.98 | 1.15 | 1.02 |
Rate per 100 pt-year (95% CI) | 20.22 (17.91, 22.83) | 14.97 (13.13, 17.06) | 6.46 (6.27, 6.65) | 6.88 (6.69, 7.08) | 27.67 (19.46, 39.34) | 28.88 (17.11, 48.77) | 28.03 (20.93, 37.55) | 35.05 (27.53, 44.61) | 27.50 (18.27, 41.38) | 32.73 (26.59, 40.28) |
Risk Factors | 0 factor | Any factor | 1 factor | 2 factors | ≥ 3 factors |
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Baseline ESA Nonusers | |||||
(N = 2226) | (N = 29,973) | (N = 10,537) | (N = 9334) | (N = 10,102) | |
MACE | |||||
Event n | 92 | 6205 | 1192 | 1679 | 3334 |
Pt-year | 5181 | 66,036 | 24,811 | 21,209 | 20,016 |
Mean follow-up years | 2.33 | 2.20 | 2.35 | 2.27 | 1.98 |
Rate per 100 pt-year (95% CI)a | 1.78 (1.45, 2.18) | 9.40 (9.17, 9.63) | 4.80 (4.54, 5.08) | 7.92 (7.55, 8.30) | 16.66 (16.10, 17.23) |
Death | |||||
Event n | 19 | 2880 | 511 | 781 | 1588 |
Pt-year | 5277 | 71,519 | 25,855 | 22,590 | 23,073 |
Mean follow-up years | 2.37 | 2.39 | 2.45 | 2.42 | 2.28 |
Rate per 100 pt-year (95% CI)a | 0.36 (0.23, 0.56) | 4.03 (3.88, 4.18) | 1.98 (1.81, 2.16) | 3.46 (3.22, 3.71) | 6.88 (6.55, 7.23) |
Baseline ESA Users | |||||
(N = 1) | (N = 108) | (N = 17) | (N = 29) | (N = 62) | |
MACE | |||||
Event n | 0 | 36 | 1 | 6 | 29 |
Pt-year | 1.1 | 182 | 36 | 58 | 88 |
Mean follow-up years | 1.05 | 1.69 | 2.12 | 2.00 | 1.42 |
Rate per 100 pt-year (95% CI)a | NA | 19.75 (14.25, 27.38) | 2.78 (0.39, 19.70) | 10.35 (4.65, 23.03) | 32.87 (22.84, 47.30) |
Death | |||||
Event n | 0 | 26 | 1 | 2 | 23 |
Pt-year | 1.1 | 201 | 36 | 60 | 106 |
Mean follow-up years | 1.05 | 1.87 | 2.12 | 2.06 | 1.70 |
Rate per 100 pt-year (95% CI)a | NA | 12.91 (8.79, 18.96) | 2.78 (0.39, 19.70) | 3.34 (0.84, 13.37) | 21.78 (14.47, 32.78) |
ESA Naives | |||||
(N = 5) | (N = 261) | (N = 30) | (N = 68) | (N = 163) | |
MACE | |||||
Event n | 0 | 77 | 3 | 19 | 55 |
Pt-year | 3.9 | 294 | 39 | 84 | 171 |
Mean follow-up years | 0.78 | 1.13 | 1.29 | 1.24 | 1.05 |
Rate per 100 pt-year (95% CI)a | NA | 26.16 (20.93, 32.71) | 7.73 (2.49, 23.97) | 22.52 (14.36, 35.30) | 32.14 (24.67, 41.86) |
Death | |||||
Event n | 0 | 42 | 2 | 9 | 31 |
Pt-year | 3.9 | 333 | 30 | 97 | 197 |
Mean follow-up years | 0.78 | 1.27 | 1.30 | 1.43 | 1.20 |
Rate per 100 pt-year (95% CI)a | NA | 12.62 (9.33, 17.08) | 5.11 (1.28, 20.45) | 9.28 (4.83, 17.84) | 15.76 (11.08, 22.41) |