Demographics and clinical characteristics of patients with 365-day baseline after s-IPTW
| Variables | Warfarin n=19 059 | Apixaban 5/2.5 mg twice daily n=22 752 | Dabigatran 150/110 mg twice daily n=8003 | Edoxaban 60/30 mg once daily n=12 592 | Rivaroxaban 15/10 mg once daily n=17 481 | ||||
| N (%) | N (%) | Std. diff.* | N (%) | Std. diff.* | N (%) | Std. diff.* | N (%) | Std. diff.* | |
| Sex category (male)† | 11 656 (61.2) | 13 912 (61.2) | −0.0002 | 4963 (62.0) | 0.0176 | 7691 (61.1) | −0.0018 | 10 672 (61.1) | −0.0022 |
| Age, years | |||||||||
| Mean±SD† | 76.1±11.9 | 76.1±10.8 | −0.0016 | 75.6±10.3 | −0.0464 | 76.2±10.8 | 0.0048 | 76.2±10.6 | 0.0074 |
| <65 | 2542 (13.3) | 2829 (12.4) | −0.0270 | 954 (11.9) | −0.0428 | 1586 (12.6) | −0.0222 | 2119 (12.1) | −0.0365 |
| 65–74 | 4707 (24.7) | 5984 (26.3) | 0.0368 | 2330 (29.1) | 0.0996 | 3249 (25.8) | 0.0254 | 4679 (26.8) | 0.0473 |
| ≥75 | 11 809 (62.0) | 13 939 (61.3) | −0.0144 | 4719 (59.0) | −0.0612 | 7757 (61.6) | −0.0074 | 10 683 (61.1) | −0.0175 |
| BMI, kg/m2 | |||||||||
| <18 | 1170 (6.1) | 1048 (4.6) | −0.0679 | 286 (3.6) | −0.1193 | 614 (4.9) | −0.0553 | 878 (5.0) | −0.0486 |
| 18 to <22 | 3925 (20.6) | 3555 (15.6) | −0.1293 | 1123 (14.0) | −0.1741 | 1858 (14.8) | −0.1536 | 2587 (14.8) | −0.1524 |
| 22 to <25 | 3541 (18.6) | 3123 (13.7) | −0.1322 | 1185 (14.8) | −0.1012 | 1572 (12.5) | −0.1690 | 2356 (13.5) | −0.1394 |
| ≥25 | 3193 (16.8) | 2671 (11.7) | −0.1438 | 1024 (12.8) | −0.1117 | 1320 (10.5) | −0.1837 | 2181 (12.5) | −0.1213 |
| Missing | 7230 (37.9) | 12 354 (54.3) | 0.3328 | 4384 (54.8) | 0.3428 | 7229 (57.4) | 0.3975 | 9479 (54.2) | 0.3313 |
| Dose group | |||||||||
| Reduced | – | 12 539 (55.1) | NA | 6557 (81.9) | NA | 9376 (74.5) | N/A | 9221 (52.8) | N/A |
| Standard | – | 10 213 (44.9) | NA | 1445 (18.1) | NA | 3216 (25.5) | N/A | 8260 (47.3) | N/A |
| CHADS2 | |||||||||
| Mean±SD | 2.3±1.6 | 2.3±1.5 | −0.0216 | 2.2±1.6 | −0.0466 | 2.3±1.6 | −0.0176 | 2.3±1.5 | −0.0211 |
| 0 | 2003 (10.5) | 2914 (12.8) | 0.0715 | 1007 (12.6) | 0.0650 | 1648 (13.1) | 0.0800 | 2107 (12.1) | 0.0487 |
| 1 | 4517 (23.7) | 5246 (23.1) | −0.0152 | 1861 (23.3) | −0.0105 | 2889 (22.9) | −0.0180 | 4089 (23.4) | −0.0073 |
| 2 | 4511 (23.7) | 4863 (21.4) | −0.0550 | 1858 (23.2) | −0.0106 | 2669 (21.2) | −0.0594 | 3881 (22.2) | −0.0349 |
| ≥3 | 8028 (42.1) | 9730 (42.8) | 0.0130 | 3276 (40.9) | −0.0240 | 5387 (42.8) | 0.0133 | 7404 (42.4) | 0.0047 |
| CHA2DS2-VASc | |||||||||
| Mean±SD | 3.8±2.1 | 3.8±1.9 | −0.0146 | 3.8±2.0 | −0.0346 | 3.8±2.0 | −0.0124 | 3.8±1.9 | −0.0127 |
| 0 | 574 (3.0) | 783 (3.4) | 0.0241 | 236 (3.0) | −0.0037 | 455 (3.6) | 0.0335 | 520 (3.0) | −0.0023 |
| 1 | 1408 (7.4) | 1732 (7.6) | 0.0085 | 656 (8.2) | 0.0302 | 1017 (8.1) | 0.0259 | 1328 (7.6) | 0.0079 |
| 2 | 2783 (14.6) | 3578 (15.7) | 0.0312 | 1239 (15.5) | 0.0246 | 1965 (15.6) | 0.0280 | 2732 (15.6) | 0.0286 |
| ≥3 | 14 293 (75.0) | 16 660 (73.2) | −0.0404 | 5871 (73.4) | −0.0372 | 9155 (72.7) | −0.0522 | 12 901 (73.8) | −0.0273 |
| PT-INR‡ (mean±SD) | 1.60±0.74 | – | – | – | – | – | – | – | – |
| Heart failure† | 7156 (37.5) | 8442 (37.1) | −0.0091 | 2944 (36.8) | −0.0158 | 4679 (37.2) | −0.0080 | 6480 (37.1) | −0.0098 |
| Coronary heart disease† | 4873 (25.6) | 5808 (25.5) | −0.0009 | 2041 (25.5) | −0.0015 | 3198 (25.4) | −0.0040 | 4407 (25.2) | −0.0082 |
| Peripheral arterial disorder† | 1447 (7.6) | 1710 (7.5) | −0.0028 | 606 (7.6) | −0.0007 | 940 (7.5) | −0.0047 | 1312 (7.5) | −0.0033 |
| Myocardial infarction† | 570 (3.0) | 676 (3.0) | −0.0013 | 238 (3.0) | −0.0013 | 370 (2.9) | −0.0033 | 516 (3.0) | −0.0024 |
| Hyperthyroidism or thyrotoxicosis | 434 (2.3) | 477 (2.1) | −0.0121 | 172 (2.1) | −0.0089 | 264 (2.1) | −0.0120 | 362 (2.1) | −0.0139 |
| Stroke, TIA or SE† | 4086 (21.4) | 4756 (20.9) | −0.0131 | 1624 (20.3) | −0.0280 | 2641 (21.0) | −0.0113 | 3696 (21.2) | −0.0071 |
| Renal dysfunction† | 1326 (7.0) | 1554 (6.8) | −0.0051 | 560 (7.0) | 0.0014 | 864 (6.9) | −0.0039 | 1224 (7.0) | 0.0017 |
| Liver dysfunction† | 2454 (12.9) | 2857 (12.6) | −0.0096 | 1034 (12.9) | 0.0013 | 1583 (12.6) | −0.0092 | 2184 (12.5) | −0.0116 |
| Bleeding diagnosis† | 2322 (12.2) | 2754 (12.1) | −0.0025 | 1002 (12.5) | 0.0101 | 1530 (12.2) | −0.0011 | 2136 (12.2) | 0.0010 |
| Hypertension† | 10 650 (55.9) | 12 527 (55.1) | −0.0165 | 4377 (54.7) | −0.0238 | 6945 (55.2) | −0.0147 | 9602 (54.9) | −0.0191 |
| Diabetes mellitus† | 5791 (30.4) | 6833 (30.0) | −0.0077 | 2414 (30.2) | −0.0049 | 3778 (30.0) | −0.0085 | 5236 (30.0) | −0.0095 |
| Cancer | 4201 (22.0) | 5252 (23.1) | 0.0249 | 1872 (23.4) | 0.0323 | 2969 (23.6) | 0.0367 | 3925 (22.5) | 0.0099 |
| Treated with antiplatelet drugs† | 4459 (23.4) | 5181 (22.8) | −0.0149 | 1781 (22.3) | −0.0272 | 2870 (22.8) | −0.0145 | 3960 (22.7) | −0.0177 |
| Treated with NSAIDs† | 5947 (31.2) | 6993 (30.7) | −0.0102 | 2474 (30.9) | −0.0062 | 3894 (30.9) | −0.0061 | 5401 (30.9) | −0.0067 |
| Treated with gastric secretion inhibitor† | 7736 (40.6) | 9113 (40.1) | −0.0110 | 3180 (39.7) | −0.0175 | 5045 (40.1) | −0.0108 | 7022 (40.2) | −0.0086 |
| Treated with statin-based drug† | 2677 (14.0) | 3200 (14.1) | 0.0006 | 1084 (13.5) | −0.0146 | 1765 (14.0) | −0.0008 | 2410 (13.8) | −0.0074 |
| Treated with antiarrhythmics | 8481 (44.5) | 9968 (43.8) | −0.0138 | 3512 (43.9) | −0.0125 | 5529 (43.9) | −0.0120 | 7677 (43.9) | −0.0117 |
| Treated with beta-blockers | 3972 (20.8) | 4651 (20.4) | −0.0099 | 1613 (20.2) | −0.0169 | 2569 (20.4) | −0.0110 | 3526 (20.2) | −0.0167 |
| Treated with heparin† | 3905 (20.5) | 4552 (20.0) | −0.0121 | 1625 (20.3) | −0.0048 | 2520 (20.0) | −0.0119 | 3555 (20.3) | −0.0039 |
| Cardioversion† | 142 (0.7) | 162 (0.7) | −0.0038 | 67 (0.8) | 0.0101 | 91 (0.7) | −0.0030 | 122 (0.7) | −0.0052 |
| Therapy days (mean±SD) | 451.5±632.9 | 395.9±412.1 | −0.1041 | 823.4±765.1 | 0.5296 | 263.0±266.7 | −0.3882 | 415.4±471.2 | −0.0647 |
*Calculated when compared with the warfarin cohort.
†Variables included in the calculation of propensity score.
‡The Japanese treatment guidelines recommend target INR ranges of 2.0–3.0 for patients aged less than 70 years and 1.6–2.6 for patients aged 70 years or older.
BMI, body mass index; NSAID, non-steroidal anti-inflammatory drug; PT-INR, prothrombin time–international normalised ratio; SE, systemic embolism; s-IPTW, inverse probability of treatment weighting with stabilised weights; TIA, transient ischaemic attack.