Table 1.
Demographic and clinical characteristics of cases of serious bleeding and matched controls within AF and DVT/PE DOAC‐treated patients; and cases with CVA/SE and matched controls within patients with AF; Clalit 2010–2020, N(%)
| Characteristic | Cases of serious bleeding and matched controls | Cases with CVA/SE and matched controls | ||||
|---|---|---|---|---|---|---|
|
Controls N = 29,764 |
Cases N = 1,587 |
P value |
Controls N = 21,685 |
Cases N = 1,116 |
P value | |
| Age a | 80.0 ± 7.9 | 80.0 ± 8.6 | 0.863 | 79.0 ± 8.6 | 78.9 ± 9.1 | 0.746 |
| Sex a , male | 14,965 (50.3) | 799 (50.3) | 0.958 | 9,538 (44.0) | 491 (44.0) | 0.994 |
| Ethnicity, Jewish | 27,766 (93.3) | 1,442 (90.9) | < 0.0001 | 19,997 (92.2) | 1,012 (90.7) | 0.063 |
| Socioeconomic status | ||||||
| Low | 8,331 (28.0) | 466 (29.4) | 0.213 | 6,173 (29.0) | 351 (32.7) | 0.002 |
| Medium | 13,12 (45.4) | 721 (45.4) | 9,911 (46.6) | 507 (47.2) | ||
| High | 7,379 (24.8) | 364 (22.9) | 5,171 (24.3) | 216 (20.1) | ||
| DOAC type a | 0.176 | 0.757 | ||||
| Apixaban | 14,048 (47.2) | 721 (45.4) | 10,406 (48.0) | 526 (47.1) | ||
| Dabigatran | 5,411 (18.2) | 316 (19.9) | 4,359 (20.1) | 234 (21.0) | ||
| Rivaroxaban | 10,305 (34.6) | 550 (34.7) | 6,920 (31.9) | 356 (31.9) | ||
| Comorbidities | ||||||
| Hyperlipidemia | 26,197 (88.0) | 1,420 (89.5) | 0.080 | 19,091 (88.0) | 1,008 (90.3) | 0.021 |
| Hypertension | 22,910 (77.0) | 1,273 (80.2) | 0.003 | 16,635 (76.7) | 915 (82.0) | < 0.0001 |
| Ischemic heart disease | 15,324 (51.5) | 909 (57.3) | < 0.0001 | 11,069 (51.0) | 644 (57.7) | < 0.0001 |
| Diabetes mellitus | 12,969 (43.6) | 785 (49.5) | < 0.0001 | 9,363 (43.2) | 570 (51.1) | < 0.0001 |
| Chronic renal failure | 6,136 (20.6) | 419 (26.4) | < .0001 | 4,339 (20.0) | 247 (22.1) | 0.084 |
| Malignancy | 6,380 (21.4) | 393 (24.8) | 0.002 | 4,457 (20.6) | 226 (20.3) | 0.807 |
| Chronic lung disease | 3,931 (13.2) | 251 (15.8) | 0.003 | 2,920 (13.5) | 155 (13.9) | 0.686 |
| Dementia | 2,803 (9.4) | 196 (12.4) | < 0.0001 | 2,040 (9.4) | 155 (13.9) | < 0.0001 |
| Parkinson's disease | 899 (3.0) | 54 (3.4) | 0.387 | 628 (2.9) | 35 (3.1) | 0.641 |
| Liver disease | 861 (2.9) | 64 (4.0) | 0.009 | 686 (3.2) | 46 (4.1) | 0.077 |
| Obesity (BMI > 25 kg/m2) | 23,334 (78.5) | 1,192 (75.3) | 0.002 | 16,826 (77.8) | 845 (76.1) | 0.162 |
| Smoking | 11,849 (39.8) | 618 (38.9) | 0.491 | 8,253 (38.1) | 428 (38.4) | 0.844 |
| Drug abuse | 76 (0.3) | 5 (0.3) | 0.607 | 82 (0.4) | 4 (0.4) | > 0.99 |
| Relevant medications use at cohort entry | ||||||
| Antiplatelet therapy | 15,924 (53.5) | 892 (56.2) | 0.035 | 11,875 (54.8) | 632 (56.6) | 0.221 |
| Proton pump inhibitors | 14,072 (47.3) | 784 (49.4) | 0.099 | 10,254 (47.3) | 544 (48.7) | 0.341 |
| H2 receptor blockers | 1,941 (6.5) | 125 (7.9) | 0.034 | 1,481 (6.8) | 100 (9.0) | 0.006 |
| Prednisone | 1,991 (6.7) | 141 (8.9) | 0.001 | 1,515 (7.0) | 85 (7.6) | 0.422 |
| Hormonal treatment | 711 (2.4) | 21 (1.3) | 0.006 | 566 (2.6) | 28 (2.5) | 0.836 |
| Laboratory values | ||||||
| Creatinine > 1.5 mg/dL | 2,190 (7.4) | 185 (11.7) | < 0.0001 | 1,699 (7.8) | 102 (9.1) | 0.115 |
| Thrombocytopenia (PLT < 100,000/mm3) | 287 (1.0) | 22 (1.4) | 0.098 | 191 (0.9) | 14 (1.3) | 0.197 |
Case‐control analysis of serious bleeding included 1,526 cases and 28,958 controls within patients with AF, and 61 cases and 806 controls within patients with DVT/PE. For 1,389 patients, (87%) 20 controls were successfully matched; for 107(6.7%) patients 10–19 controls were matched; for 91 patients (5.7%) 1–9 controls were successfully matched; for other 9 bleeding cases (0.56%) controls could not be matched and were not included. Within bleeding cases 58.1% received reduced‐dose DOAC at cohort entry and the rest received full dose; while within controls 53.0% received reduced‐dose and the rest received full dose (P < 0.0001). In CVA/SE case‐control analysis within AF patients, each of 1,024 cases (91.8%) was successfully matched to 20 controls; for 61 (5.5%) cases only 10–19 controls were successfully matched to each case; and for 31 (2.8%) cases only 1–9 controls could be successfully matched to each case. Within CVA/SE cases 55.7% received reduced‐dose DOAC at cohort entry and the rest received full dose; while within controls 53.3% received reduced‐dose DOAC, and the rest received full dose (P = 0.11).
AF, atrial fibrillation; BMI, body mass index; CVA/SE, cerebrovascular accident/systemic emboli; DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; PE, pulmonary embolism.
Matching variables, along with indication for DOAC‐treatment, year of cohort entry, and length of follow up.