Why carry out this study?
|
Venous thromboembolism (VTE) is a frequent and serious medical event associated with a substantial risk of adverse outcomes. |
As previous studies on anticoagulation treatment trends were mostly limited to inpatients, this study intended to examine the clinical management and demographic characteristics of patients with VTE in Japan, including outpatients, to identify treatment trends from 2011 to 2018, and to assess the adherence to current guidelines. |
What was learned from the study?
|
About half of the patients diagnosed with VTE had been hospitalized for illnesses other than VTE, the proportion of outpatients treated for VTE gradually increased, and the presence of cancer did not appear to be a barrier to anticoagulant choice or to outpatient treatment. |
The duration of anticoagulation was shorter and more variable than that specified by current guidelines, and the treatment with direct oral anticoagulants (DOACs) may not always follow the suggested initial treatment strategy. |
The study findings suggest the importance of developing and further utilizing in-hospital manuals for thrombosis prevention, and future studies should examine whether the current use of DOACs, with possible deviations from guideline-recommended use and shorter anticoagulation regimens, improves patient outcomes. |
Introduction
Methods
Data Source
Study Population
Protection of Human Participants
Definitions
Anticoagulants
Statistical Analysis
Results
Study Population
Temporal Trends in the Proportions of Inpatients and Outpatients
Differences in Patient Characteristics between Inpatients and Outpatients
DVT | |||||||
---|---|---|---|---|---|---|---|
Patient characteristics | Standardized difference | ||||||
All patients with DVT | Outpatients with DVT | DVT inpatients 1 | DVT inpatients 2 | Outpatients versus inpatients 1 | Outpatients versus inpatients 2 | Inpatients 1 versus inpatients 2 | |
Number of patients (%)a | 63,815 (100.0) | 22,661 (35.5) | 4422 (6.9) | 36,732 (57.6) | 0.7469 | 0.4543 | 1.2910 |
Female (%)b | 41,466 (65.0) | 14,963 (66.0) | 2788 (63.0) | 23,715 (64.6) | 0.0627 | 0.0294 | 0.0333 |
Age (years), mean ± SD | 71.0 ± 14.7 | 68.8 ± 13.5 | 70.0 ± 16.8 | 72.4 ± 14.9 | 0.0787 | 0.2532 | 0.1552 |
Age group (%)b | |||||||
20–29 | 768 (1.2) | 205 (0.9) | 109 (2.5) | 454 (1.2) | 0.1240 | 0.0294 | 0.0966 |
30–39 | 2026 (3.2) | 683 (3.0) | 235 (5.3) | 1108 (3.0) | 0.1155 | 0.0000 | 0.1155 |
40–49 | 3586 (5.6) | 1476 (6.5) | 281 (6.4) | 1829 (5.0) | 0.0041 | 0.0645 | 0.0604 |
50–59 | 5654 (8.9) | 2424 (10.7) | 360 (8.1) | 2870 (7.8) | 0.0892 | 0.1002 | 0.0111 |
60–69 | 12,708 (19.9) | 5440 (24.0) | 782 (17.7) | 6486 (17.7) | 0.1556 | 0.1556 | 0.0000 |
70–79 | 18,854 (29.5) | 7408 (32.7) | 1144 (25.9) | 10,302 (28.0) | 0.1498 | 0.1024 | 0.0473 |
80+ | 20,219 (31.7) | 5025 (22.2) | 1511 (34.2) | 13,683 (37.3) | 0.2691 | 0.3349 | 0.0647 |
Comorbidities (%)b | |||||||
Cancer (all) | 19,035 (29.8) | 7278 (32.1) | 1032 (23.3) | 10,725 (29.2) | 0.1976 | 0.0629 | 0.1344 |
Active cancer (%)a | 17,642 (100.0) | 6810 (38.6) | 918 (5.2) | 9914 (56.2) | 0.8828 | 0.3581 | 1.3269 |
Active cancer, type (%)c | |||||||
Gastrointestinal tract cancer | 5938 (33.7) | 2309 (33.9) | 323 (35.2) | 3306 (33.3) | 0.0273 | 0.0127 | 0.0400 |
Gallbladder, liver, pancreas cancer | 1896 (10.7) | 596 (8.8) | 97 (10.6) | 1203 (12.1) | 0.0608 | 0.1080 | 0.0473 |
Respiratory cancer | 1814 (10.3) | 620 (9.1) | 83 (9.0) | 1111 (11.2) | 0.0035 | 0.0696 | 0.0731 |
Breast cancer | 1155 (6.5) | 540 (7.9) | 79 (8.6) | 536 (5.4) | 0.0254 | 0.1005 | 0.1257 |
Uterine/ovarian cancer | 3569 (20.2) | 1703 (25.0) | 128 (13.9) | 1738 (17.5) | 0.2832 | 0.1841 | 0.0991 |
Prostate cancer | 958 (5.4) | 388 (5.7) | 66 (7.2) | 504 (5.1) | 0.0611 | 0.0265 | 0.0875 |
Kidney or bladder cancer | 1090 (6.2) | 438 (6.4) | 69 (7.5) | 583 (5.9) | 0.0433 | 0.0208 | 0.0640 |
Metastatic cancer | 5366 (30.4) | 1800 (26.4) | 351 (38.2) | 3215 (32.4) | 0.2544 | 0.1320 | 0.1216 |
Other active cancer | 3555 (20.2) | 1068 (15.7) | 197 (21.5) | 2290 (23.1) | 0.1495 | 0.1880 | 0.0384 |
Diabetes mellitus | 14,544 (22.8) | 4574 (20.2) | 843 (19.1) | 9127 (24.8) | 0.0277 | 0.1103 | 0.1380 |
Dyslipidemia | 10,928 (17.1) | 3368 (14.9) | 907 (20.5) | 6653 (18.1) | 0.1471 | 0.0863 | 0.0608 |
Hypertension | 22,855 (35.8) | 6217 (27.4) | 1707 (38.6) | 14,931 (40.6) | 0.2399 | 0.2814 | 0.0409 |
History of CAD | 6961 (10.9) | 2351 (10.4) | 414 (9.4) | 4196 (11.4) | 0.0335 | 0.0321 | 0.0656 |
Heart failure | 9229 (14.5) | 3013 (13.3) | 660 (14.9) | 5556 (15.1) | 0.0460 | 0.0516 | 0.0056 |
Kidney disease | 2157 (3.4) | 664 (2.9) | 138 (3.1) | 1355 (3.7) | 0.0117 | 0.0448 | 0.0331 |
History of stroke | 6079 (9.5) | 1206 (5.3) | 247 (5.6) | 4626 (12.6) | 0.0132 | 0.2578 | 0.2452 |
Connective tissue disease | 9908 (15.5) | 3457 (15.3) | 645 (14.6) | 5806 (15.8) | 0.0196 | 0.0138 | 0.0334 |
History of bleeding | 16,728 (26.2) | 4330 (19.1) | 892 (20.2) | 11,506 (31.3) | 0.0277 | 0.2838 | 0.2559 |
Fracture | 10,653 (16.7) | 1032 (4.6) | 288 (6.5) | 9333 (25.4) | 0.0831 | 0.6089 | 0.5343 |
Surgery | 9478 (14.9) | 1527 (6.7) | 295 (6.7) | 7656 (20.8) | 0.0000 | 0.4183 | 0.4183 |
Trauma | 13,922 (21.8) | 2062 (9.1) | 503 (11.4) | 11,357 (30.9) | 0.0759 | 0.5664 | 0.4917 |
Pregnancy | 627 (1.0) | 113 (0.5) | 70 (1.6) | 444 (1.2) | 0.1081 | 0.0763 | 0.0341 |
PE | |||||||
---|---|---|---|---|---|---|---|
Standardized difference | |||||||
All patients with PE | Outpatients with PE | PE inpatients 1 | PE inpatients 2 | Outpatients versus inpatients 1 | Outpatients versus inpatients 2 | Inpatients 1 versus inpatients 2 | |
Number of patients (%)a | 15,515 (100.0) | 1395 (9.0) | 6409 (41.3) | 7711 (49.7) | 0.8021 | 0.9991 | 0.1693 |
Female (%)b | 9224 (59.5) | 742 (53.2) | 3855 (60.1) | 4627 (60.0) | 0.1396 | 0.1375 | 0.0020 |
Age (years), mean ± SD | 70.3 ± 15.0 | 68.3 ± 13.7 | 68.5 ± 15.4 | 72.2 ± 14.7 | 0.0137 | 0.2745 | 0.2458 |
Age group (%)b | |||||||
20–29 | 185 (1.2) | 18 (1.3) | 76 (1.2) | 91 (1.2) | 0.0090 | 0.0090 | 0.0000 |
30–39 | 431 (2.8) | 39 (2.8) | 228 (3.6) | 164 (2.1) | 0.0455 | 0.0453 | 0.0902 |
40–49 | 1161 (7.5) | 102 (7.3) | 613 (9.6) | 446 (5.8) | 0.0828 | 0.0607 | 0.1429 |
50–59 | 1582 (10.2) | 158 (11.3) | 740 (11.5) | 684 (8.9) | 0.0063 | 0.0797 | 0.0860 |
60–69 | 3054 (19.7) | 344 (24.7) | 1305 (20.4) | 1405 (18.2) | 0.1030 | 0.1589 | 0.0558 |
70–79 | 4278 (27.6) | 436 (31.3) | 1720 (26.8) | 2122 (27.5) | 0.0992 | 0.0835 | 0.0157 |
80+ | 4824 (31.1) | 298 (21.4) | 1727 (26.9) | 2799 (36.3) | 0.1288 | 0.3334 | 0.2032 |
Comorbidities (%)b | |||||||
Cancer (all) | 4471 (28.8) | 611 (43.8) | 1318 (20.6) | 2542 (33.0) | 0.5126 | 0.2234 | 0.2827 |
Active cancer (%)a | 3995 (100.0) | 548 (13.7) | 1146 (28.7) | 2301 (57.6) | 0.3733 | 1.0312 | 0.6100 |
Active cancer, type (%)c | |||||||
Gastrointestinal tract cancer | 1354 (33.9) | 202 (36.9) | 371 (32.4) | 781 (33.9) | 0.0947 | 0.0628 | 0.0319 |
Gallbladder, liver, pancreas cancer | 442 (11.1) | 40 (7.3) | 138 (12.0) | 264 (11.5) | 0.1597 | 0.1443 | 0.0155 |
Respiratory cancer | 801 (20.1) | 150 (27.4) | 179 (15.6) | 472 (20.5) | 0.2902 | 0.1622 | 0.1277 |
Breast cancer | 277 (6.9) | 30 (5.5) | 107 (9.3) | 140 (6.1) | 0.1455 | 0.0257 | 0.1203 |
Uterine/ovarian cancer | 473 (11.8) | 68 (12.4) | 143 (12.5) | 262 (11.4) | 0.0030 | 0.0309 | 0.0339 |
Prostate cancer | 277 (6.9) | 32 (5.8) | 104 (9.1) | 141 (6.1) | 0.1259 | 0.0127 | 0.1134 |
Kidney or bladder cancer | 194 (4.9) | 35 (6.4) | 62 (5.4) | 97 (4.2) | 0.0424 | 0.0983 | 0.0562 |
Metastatic cancer | 1542 (38.6) | 176 (32.1) | 437 (38.1) | 929 (40.4) | 0.1260 | 0.1733 | 0.0471 |
Other active cancer | 691 (17.3) | 87 (15.9) | 169 (14.7) | 435 (18.9) | 0.0333 | 0.0792 | 0.1125 |
Diabetes mellitus | 3083 (19.9) | 276 (19.8) | 1106 (17.3) | 1701 (22.1) | 0.0643 | 0.0565 | 0.1209 |
Dyslipidemia | 2911 (18.8) | 233 (16.7) | 1379 (21.5) | 1299 (16.8) | 0.1223 | 0.0027 | 0.1197 |
Hypertension | 5757 (37.1) | 433 (31.0) | 2456 (38.3) | 2868 (37.2) | 0.1539 | 0.1311 | 0.0227 |
History of CAD | 1733 (11.2) | 185 (13.3) | 592 (9.2) | 956 (12.4) | 0.1300 | 0.0269 | 0.1032 |
Heart failure | 3489 (22.5) | 298 (21.4) | 1600 (25.0) | 1591 (20.6) | 0.0854 | 0.0196 | 0.1050 |
Kidney disease | 462 (3.0) | 47 (3.4) | 190 (3.0) | 225 (2.9) | 0.0227 | 0.0286 | 0.0059 |
History of stroke | 1298 (8.4) | 60 (4.3) | 305 (4.8) | 933 (12.1) | 0.0240 | 0.2872 | 0.2648 |
Connective tissue disease | 2132 (13.7) | 213 (15.3) | 754 (11.8) | 1165 (15.1) | 0.1024 | 0.0056 | 0.0968 |
History of bleeding | 4042 (26.1) | 301 (21.6) | 1299 (20.3) | 2442 (31.7) | 0.0319 | 0.2299 | 0.2621 |
Fracture | 1763 (11.4) | 60 (4.3) | 339 (5.3) | 1364 (17.7) | 0.0468 | 0.4384 | 0.3962 |
Surgery | 1631 (10.5) | 77 (5.5) | 286 (4.5) | 1268 (16.4) | 0.0459 | 0.3545 | 0.3966 |
Trauma | 2480 (16.0) | 109 (7.8) | 603 (9.4) | 1768 (22.9) | 0.0571 | 0.4284 | 0.3732 |
Pregnancy | 44 (0.3) | 0 (0.0) | 11 (0.2) | 33 (0.4) | 0.0633 | 0.0896 | 0.0366 |
Changes in VTE Treatment
Drug Selection and Patient Characteristics
All | Apixaban | Edoxaban | Rivaroxaban | Warfarin | Heparin or fondaparinuxa | |
---|---|---|---|---|---|---|
All patients with DVT | 30,924 (100.0) | 2503 (8.1) | 11,216 (36.3) | 2014 (6.5) | 1599 (5.2) | 13,592 (44.0) |
Outpatients with DVT | 11,688 (100.0) | 1138 (9.7) | 5262 (45.0) | 986 (8.4) | 490 (4.2) | 3812 (32.6) |
DVT inpatients 1 | 1569 (100.0) | 182 (11.6) | 161 (10.3) | 155 (9.9) | 19 (1.2) | 1052 (67.0) |
DVT inpatients 2 | 17,667 (100.0) | 1183 (6.7) | 5793 (32.8) | 873 (4.9) | 1090 (6.2) | 8728 (49.4) |
DVT patients with active cancer | 8147 (100.0) | 579 (7.1) | 2498 (30.7) | 468 (5.7) | 269 (3.3) | 4333 (53.2) |
DVT patients without active cancer | 22,777 (100.0) | 1924 (8.4) | 8718 (38.3) | 1546 (6.8) | 1330 (5.8) | 9259 (40.7) |
All patients with PE | 6900 (100.0) | 646 (9.4) | 908 (13.2) | 492 (7.1) | 189 (2.7) | 4665 (67.6) |
Outpatients with PE | 790 (100.0) | 147 (18.6) | 236 (29.9) | 99 (12.5) | 34 (4.3) | 274 (34.7) |
PE inpatients 1 | 2628 (100.0) | 248 (9.4) | 128 (4.9) | 227 (8.6) | 10 (0.4) | 2015 (76.7) |
PE inpatients 2 | 3482 (100.0) | 251 (7.2) | 544 (15.6) | 166 (4.8) | 145 (4.2) | 2376 (68.2) |
PE patients with active cancer | 1780 (100.0) | 189 (10.6) | 311 (17.5) | 116 (6.5) | 31 (1.7) | 1133 (63.7) |
PE patients without active cancer | 5120 (100.0) | 457 (8.9) | 597 (11.7) | 376 (7.3) | 158 (3.1) | 3532 (69.0) |
Duration of Anticoagulation Therapy
All patients with DVT | Outpatients with DVT | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
A | E | R | W | Ha | Fa | A | E | R | W | Ha | Fa | |
Patients, n (%) | 2503 (8.1) | 11,216 (36.2) | 2014 (6.5) | 1599 (5.2) | 13,425 (43.3) | 252 (0.8) | 1138 (9.7) | 5262 (44.9) | 986 (8.4) | 490 (4.2) | 3770 (32.3) | 61 (0.5) |
Days on treatmentb | ||||||||||||
Q1 | 22.0 | 12.0 | 21.0 | 14.0 | 1.0 | 4.0 | 32.0 | 12.0 | 30.0 | 23.0 | 1.0 | 4.0 |
Q2 | 58.0 | 31.0 | 62.0 | 34.0 | 4.0 | 5.0 | 89.0 | 49.0 | 91.0 | 73.5 | 1.0 | 5.0 |
Q3 | 145.0 | 98.0 | 154.0 | 102.0 | 10.0 | 8.0 | 190.0 | 147.0 | 210.0 | 210.0 | 7.0 | 7.0 |
DVT inpatients 1 | DVT inpatients 2 | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
A | E | R | W | Ha | Fa | A | E | R | W | Ha | Fa | |
Patients, n (%) | 182 (11.6) | 161 (10.2) | 155 (9.8) | 19 (1.2) | 1030 (65.2) | 33 (2.1) | 1183 (6.7) | 5793 (32.7) | 873 (4.9) | 1090 (6.2) | 8625 (48.8) | 158 (0.9) |
Days on treatmentb | ||||||||||||
Q1 | 27.0 | 16.0 | 24.0 | 8.0 | 2.0 | 3.0 | 16.0 | 13.0 | 17.0 | 14.0 | 1.0 | 4.0 |
Q2 | 73.5 | 36.0 | 64.0 | 46.0 | 5.0 | 5.0 | 40.0 | 25.0 | 37.0 | 28.0 | 5.0 | 5.5 |
Q3 | 181.0 | 135.0 | 202.0 | 188.0 | 10.0 | 6.0 | 90.0 | 69.0 | 91.0 | 67.0 | 12.0 | 10.0 |
DVT patients with active cancer | DVT patients without active cancer | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
A | E | R | W | Ha | Fa | A | E | R | W | Ha | Fa | |
Patients, n (%) | 579 (7.1) | 2498 (30.4) | 468 (5.7) | 269 (3.3) | 4274 (52.1) | 120 (1.5) | 1924 (8.4) | 8718 (38.2) | 1546 (6.8) | 1330 (5.8) | 9151 (40.1) | 132 (0.6) |
Days on treatmentb | ||||||||||||
Q1 | 28.0 | 31.0 | 28.5 | 21.0 | 1.0 | 4.0 | 21.0 | 10.0 | 21.0 | 14.0 | 1.0 | 4.0 |
Q2 | 80.0 | 87.0 | 84.0 | 50.0 | 4.0 | 5.0 | 52.5 | 23.0 | 56.0 | 32.0 | 4.0 | 6.0 |
Q3 | 207.0 | 224.0 | 226.5 | 149.0 | 10.0 | 6.0 | 129.0 | 79.0 | 133.0 | 100.0 | 10.0 | 10.0 |
All patients with PE | Outpatients with PE | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
A | E | R | W | Ha | Fa | A | E | R | W | Ha | Fa | |
Patients, n (%) | 646 (9.3) | 908 (13.1) | 492 (7.1) | 189 (2.7) | 4599 (66.3) | 99 (1.4) | 147 (18.6) | 236 (29.8) | 99 (12.5) | 34 (4.3) | 270 (34.1) | 5 (0.6) |
Days on treatmentb | ||||||||||||
Q1 | 24.0 | 17.5 | 29.0 | 12.0 | 1.0 | 4.0 | 64.0 | 42.0 | 53.0 | 14.0 | 1.0 | 1.0 |
Q2 | 70.0 | 48.0 | 93.0 | 26.0 | 5.0 | 5.0 | 131.0 | 129.5 | 121.0 | 39.0 | 1.0 | 4.0 |
Q3 | 202.0 | 168.0 | 218.5 | 56.0 | 11.0 | 6.0 | 280.0 | 245.0 | 258.0 | 117.0 | 6.0 | 5.0 |
PE inpatients 1 | PE inpatients 2 | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
A | E | R | W | Ha | Fa | A | E | R | W | Ha | Fa | |
Patients, n (%) | 248 (9.4) | 128 (4.8) | 227 (8.6) | 10 (0.4) | 1987 (75.1) | 46 (1.7) | 251 (7.2) | 544 (15.6) | 166 (4.7) | 145 (4.2) | 2342 (67.3) | 48 (1.4) |
Days on treatmentb | ||||||||||||
Q1 | 76.0 | 21.0 | 31.0 | 2.0 | 2.0 | 3.0 | 19.0 | 14.0 | 21.0 | 11.0 | 1.0 | 4.0 |
Q2 | 229.5 | 53.5 | 103.0 | 13.5 | 5.0 | 5.0 | 40.0 | 33.0 | 52.0 | 25.0 | 6.0 | 5.0 |
Q3 | 229.5 | 212.0 | 243.0 | 54.0 | 9.0 | 6.0 | 120.0 | 104.0 | 129.0 | 48.0 | 13.0 | 7.0 |
PE patients with active cancer | PE patients without active cancer | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
A | E | R | W | Ha | Fa | A | E | R | W | Ha | Fa | |
Patients, n (%) | 189 (10.6) | 311 (17.4) | 116 (6.5) | 31 (1.7) | 1104 (62.0) | 38 (2.1) | 457 (8.9) | 597 (11.6) | 376 (7.3) | 158 (3.1) | 3495 (67.9) | 61 (1.2) |
Days on treatmentb | ||||||||||||
Q1 | 35.0 | 30.0 | 33.0 | 17.0 | 1.0 | 5.0 | 21.0 | 14.0 | 28.5 | 11.0 | 1.0 | 3.0 |
Q2 | 110.0 | 117.0 | 116.5 | 38.0 | 6.0 | 5.0 | 57.0 | 33.0 | 84.5 | 25.0 | 5.0 | 5.0 |
Q3 | 258.0 | 245.0 | 249.0 | 97.0 | 14.0 | 6.0 | 182.0 | 110.0 | 204.5 | 48.0 | 10.0 | 7.0 |