Baseline demographics and co-morbid conditions of the entire derivation cohort, and separately for bleeding cases, and for patients with no major bleeding, at apixaban initiation
| Characteristics | All (N=28 055) | Cases (N=662) | Without bleeding (N=27 393) |
| Age, mean (SD) | 78.7 (9.0) | 80.2 (7.8) | 78.7 (9.0) |
| Age categories (years) | |||
| <65 | 2122 (7.6%) | 24 (3.6%) | 2098 (7.7%) |
| 65–74 | 6392 (22.8%) | 127 (19.2%) | 6265 (22.9%) |
| ≥75 | 19 541 (69.7%) | 511 (77.2%) | 19 030 (69.5%) |
| Sex—male | 13 483 (48.1%) | 388 (58.6%) | 13 095 (47.8%) |
| Smoking | 10 491 (37.4%) | 268 (40.5%) | 10 223 (37.3%) |
| BMI, mean (SD)* | 29.5 (5.8) | 29.1 (5.8) | 29.5 (5.8) |
| Alcohol abuse | 246 (0.9%) | 9 (1.4%) | 237 (0.9%) |
| Hypertension | 25 282 (90.1%) | 628 (94.9%) | 24 654 (90.0%) |
| Congestive heart failure | 9136 (32.6%) | 238 (36.0%) | 8898 (32.5%) |
| Diabetes mellitus | 12 991 (46.3%) | 341 (51.5%) | 12 650 (46.2%) |
| Chronic obstructive pulmonary disease | 4219 (15.0%) | 105 (15.9%) | 4114 (15.0%) |
| Active cancer | 1111 (4.0%) | 34 (5.1%) | 1077 (3.9%) |
| Prior major bleeding, any | 12 325 (43.9%) | 350 (52.9%) | 11 975 (43.7%) |
| Prior major GI bleeding | 8254 (29.4%) | 246 (37.2%) | 8008 (29.2%) |
| Prior major intracranial bleeding | 5828 (20.8%) | 167 (25.2%) | 5661 (20.7%) |
| GI disease, any | 6681 (23.8%) | 195 (29.5%) | 6486 (23.7%) |
| Peptic ulcer | 4667 (16.6%) | 129 (19.5%) | 4538 (16.6%) |
| Crohn’s disease | 102 (0.4%) | 4 (0.6%) | 98 (0.4%) |
| Ulcerative colitis | 156 (0.6%) | 7 (1.1%) | 149 (0.5%) |
| Diverticulosis | 1260 (4.5%) | 43 (6.5%) | 1217 (4.4%) |
| GI surgery | 1481 (5.3%) | 42 (6.3%) | 1439 (5.3%) |
| Fall risk, any | 11 034 (39.3%) | 305 (46.1%) | 10 729 (39.2%) |
| Fall | 7010 (25.0%) | 185 (27.9%) | 6825 (24.9%) |
| Gait problem | 4950 (17.6%) | 151 (22.8%) | 4799 (17.5%) |
| Hip fracture | 1823 (6.5%) | 41 (6.2%) | 1782 (6.5%) |
| Dementia | 2682 (9.6%) | 74 (11.2%) | 2608 (9.5%) |
| Parkinson’s disease | 856 (3.1%) | 35 (5.3%) | 821 (3.0%) |
| Liver disease | 1087 (3.9%) | 29 (4.4%) | 1058 (3.9%) |
| eGFR, mean (SD), mL/min | 63.6 (29.2) | 58.1 (24.6) | 63.8 (29.3) |
| eGFR categories, mL/min | |||
| ≥90 | 4439 (15.8%) | 69 (10.4%) | 4370 (16.0%) |
| 89–60 | 8781 (31.3%) | 188 (28.4%) | 8593 (31.4%) |
| 59–30 | 12 778 (45.5%) | 340 (51.4%) | 12 438 (45.4%) |
| ≤29 | 2057 (7.3%) | 65 (9.8%) | 1992 (7.3%) |
| Serum total cholesterol categories,† mg/dL | |||
| <160 | 14 877 (53.1%) | 404 (61.1%) | 14 473 (52.9%) |
| 160–199 | 8829 (31.5%) | 181 (27.4%) | 8648 (31.6%) |
| 200–239 | 3227 (11.5%) | 62 (9.4%) | 3165 (11.6%) |
| ≥240 | 1065 (3.8%) | 14 (2.1%) | 1051 (3.8%) |
| Serum LDL-C categories,‡mg/dL | |||
| <70 | 8028 (28.8%) | 231 (35.1%) | 7797 (28.7%) |
| 70–99 | 11 045 (39.6%) | 258 (39.2%) | 10 787 (39.6%) |
| 100–129 | 5781 (20.7%) | 112 (17.0%) | 5669 (20.8%) |
| 130–159 | 2201 (7.9%) | 40 (6.1%) | 2161 (7.9%) |
| ≥160 | 817 (2.9%) | 17 (2.6%) | 800 (2.9%) |
| Serum platelets count§ | |||
| Normal/mild thrombocytopaenia (≥100×103/µL) | 27 703 (98.8%) | 645 (97.4%) | 27 058 (98.8%) |
| Moderate/severe thrombocytopaenia (<99×103/µL) | 343 (1.2%) | 17 (2.6%) | 326 (1.2%) |
| Anaemia (Hb <13 g/dL (male), <12 g/dL (female)) | 12 005 (42.8%) | 358 (54.1%) | 11 647 (42.5%) |
| HAS-BLED score | |||
| ≤1 | 1231 (4.4%) | 13 (2.0%) | 1218 (4.4%) |
| 2 | 5761 (20.5%) | 85 (12.8%) | 5676 (20.7%) |
| 3 | 12 011 (42.8%) | 293 (44.3%) | 11 718 (42.8%) |
| ≥4 | 9052 (32.3%) | 271 (40.9%) | 8781 (32.1%) |
| CHA2DS2-VASc score | |||
| ≤1 | 489 (1.7%) | 3 (0.5%) | 486 (1.8%) |
| 2 | 1494 (5.3%) | 17 (2.6%) | 1477 (5.4%) |
| 3 | 3872 (13.8%) | 70 (10.6%) | 3802 (13.9%) |
| 4 | 6500 (23.2%) | 133 (20.1%) | 6367 (23.2%) |
| 5 | 6504 (23.2%) | 169 (25.5%) | 6335 (23.1%) |
| 6 | 4825 (17.2%) | 141 (21.3%) | 4684 (17.1%) |
| 7 | 2764 (9.9%) | 91 (13.7%) | 2673 (9.8%) |
| ≥8 | 1607 (5.7%) | 38 (5.7%) | 1569 (5.7%) |
| Concurrent antiplatelet therapy | 1820 (6.5%) | 67 (10.1%) | 1753 (6.4%) |
| Proton pump inhibitor | 13 914 (49.6%) | 351 (53.0%) | 13 563 (49.5%) |
| Moderate CYP3A4/Pgp inhibitor therapy | 6016 (21.4%) | 128 (19.3%) | 5888 (21.5%) |
| Strong CYP3A4/Pgp inhibitor therapy | 340 (1.2%) | 6 (0.9%) | 334 (1.2%) |
During follow-up, a total of 662 patients received a diagnosis of a major bleeding event. There were 299 GI bleeding events, 97 intracranial bleeding events, 260 other bleeding events, 5 with diagnoses of GI bleeding and other bleeding in the same hospitalisation and 1 with diagnoses of GI and intracranial bleeding in the same hospitalisation.
n(%), unless otherwise noted.
*BMI data were missing for 37 (0.1%) patients.
†Serum total cholesterol data were missing for 57 (0.2%) patients
‡Serum LDL-C data were missing for 183 (0.6%) patients.
§Platelet count data were missing for 9 (0.03%) patients.
¶HAS-BLED is a scoring system, ranging from 0 to 9 points, that includes 9 risk factors, each contributes 1 point for the score: hypertension, abnormal renal function, abnormal liver function, previous stroke, previous major bleeding or predisposition for bleeding, labile international normalized ratio (INR), elderly (age >65), drugs (antiplatelet agents or non-steroidal anti-inflammatory drugs (NSAIDs) or alcohol consumption.10 INR values are used for HAS-BLED score calculation only among patients treated with vitamin K antagonists and are not relevant for NOAC treatment, hence INR was not considered for calculation of HAS-BLED score in our cohort.
BMI, body mass index; CYP3A4/Pgp, cytochrome P 3A4/P-glycoprotein; eGFR, estimated glomerular filtration rate; GI, gastrointestinal; HAS-BLED, Hypertension, Abnormal liver/renal function, Stroke history, Bleeding history or predisposition, Labile INR, Elderly, Drug/alcohol usage; LDL-C, low-density lipoprotein cholesterol; NOAC, new oral anticoagulant.