Table 1.
Characteristics of the Study Participants
| All Study Participants | Normal Responders | Sensitive Responders | Highly Sensitive Responders | |
|---|---|---|---|---|
| Number of participants | 2508 | 1627 | 802 | 79 |
| Sex, female, n (%) | 1133 (45.2) | 726 (44.6) | 374 (46.6) | 33 (41.8) |
| Age, years, mean (sd) | 68.8 (10.4) | 68.8 (10.4) | 68.9 (10.5) | 67.9 (9.1) |
| Indication for warfarin use | ||||
| Atrial fibrillation, n (%) | 1596 (63.6) | 1028 (63.2) | 511 (63.7) | 57 (72.1) |
| Vascular disease, n (%) | 352 (14.0) | 235 (14.4) | 107 (13.4) | 10 (12.7) |
| Pulmonary embolism, n (%) | 199 (8.0) | 122 (7.5) | 74 (9.2) | 3 (3.8) |
| Stroke or atherosclerosis in cerebral arteries, n (%) | 127 (5.1) | 78 (4.8) | 45 (5.6) | 4 (5.1) |
| Phlebitis or thrombophlebitis, n (%) | 181 (7.2) | 124 (7.6) | 52 (6.5) | 5 (6.3) |
| Other venous thrombosis, n (%) | 53 (2.1) | 40 (2.5) | 13 (1.6) | 0 |
| VKORC1 | ||||
| GG, n (%) | 961 (38.3) | |||
| AG, n (%) | 1183 (47.2) | |||
| AA, n (%) | 364 (14.5) | |||
| CYP2C9 | ||||
| CYP2C9*1/*1, n (%) | 1690 (67.4) | |||
| CYP2C9*1/*2, n (%) | 473 (18.9) | |||
| CYP2C9*1/*3, n (%) | 274 (10.9) | |||
| CYP2C9*2/*2, n (%) | 24 (1.0) | |||
| CYP2C9*2/*3, n (%) | 36 (1.4) | |||
| CYP2C9*3/*3, n (%) | 11 (0.4) | |||
| Exposure time, days, median [IQR] | 352 [123–1200] | 372 [137–1256] | 333 [116–1110] | 254 [96–843] |
| Changed to DOAC, n (%) | 148 (5.9) | 110 (6.8) | 37 (4.6) | 1 (1.3) |
| Changed to heparin products, n (%) | 413 (16.5) | 277 (17.0) | 127 (15.8) | 9 (11.4) |
| Interacting drugs | ||||
| Increasing risk of bleeding events, n (%) | 1833 (73.1) | 1195 (73.5) | 581 (72.4) | 57 (72.2) |
| Increasing risk of thromboembolic events, n (%) | 16 (0.6) | 11 (0.7) | 5 (0.6) | 0 |
| Kidney function, GFR, mean (sd) | 79.1 (19.0) missing=325 | 79.3 (19.2) missing=211 | 79.0 (18.8) missing=99 | 77.6 (18.7) missing=15 |
| Diagnosis of cancer a, n (%) | 492 (19.6) | 333 (20.5) | 150 (18.7) | 9 (11.4) |
| Genotyped in the clinic b, n (%) | 7 (0.3) | 5 (0.3) | 1 (0.1) | 1 (1.3) |
| Daily dose, mg/d, median [IQR] | 5.0 [3.7–6.7] | 5.5 [4.3–7.1] | 4.0 [3.0–5.3] | 2.6 [1.9–5.0] |
Notes: aCancer diagnosed during the warfarin exposure or up to 2 years before the warfarin initiation; bA pharmacogenetic test for CYP2C9 and VKORC1 performed to guide warfarin dosing.
Abbreviations: DOAC, direct oral anticoagulant; GFR, glomerular filtration rate; IQR, interquartile range; SD, standard deviation.