Background
Methods
Study cohort
Information on anticoagulant usage
Statistical analysis
Results
Population characteristics
Pre-diagnostic status | Post-diagnostic status | ||||||
---|---|---|---|---|---|---|---|
No anticoagulation | Warfarin | Other anticoagulants | No anticoagulation | Warfarin | Other anticoagulants | ||
n of men in the study population | 5601 | 570 | 366 | 4485 | 1074 | 978 | |
Mean age at diagnosis | 67 | 70 | 70 | 67 | 68 | 67 | |
PCa deaths | 624 (11.1%) | 65 (11.4%) | 39 (10.7%) | 509 (11.3%) | 121 (11.3%) | 98 (10.0%) | |
Median age at death (years) | 73 | 76** | 76** | 72 | 75** | 74** | |
Median follow-up from diagnosis to PCa death (years) | 4.5 | 4.5 | 4.5 | 3.9 | 4.8 | 5.8 | |
EAU prostate cancer risk-groupb
| |||||||
High-grade | 1661 (29.6%) | 181 (31.8%) | 109 (29.8%) | 1353 (30.2%) | 330 (30.7%) | 268 (27.4%) | |
Low-/Intermediate-grade | 3940 (70.3%) | 389 (68.2%) | 257 (70.2%) | 3132 (69.8%) | 744 (69.3%) | 710 (72.6%) | |
Primary therapya
| |||||||
Radical prostatectomy | 1575 (28.1%) | 38 (6.7%)** | 39 (10.7%)** | 1141 (25.4%) | 203 (18.9%)** | 308 (31.5%)** | |
EBRT | 2019 (36.0%) | 255 (44.7%) | 149 (40.7%) | 1647 (36.7%) | 444 (41.3%) | 332 (33.9%) | |
Hormonal treatment | 2197 (39.2%) | 303 (53.2%)** | 169 (46.2%)** | 1814 (40.4%) | 490 (45.6%)** | 365 (37.3%)** | |
Active surveillance or watchful waiting | 957 (17.1%) | 113 (19,8%) | 82 (22.4%) | 796 (17.7%) | 195 (18,2%) | 161 (16.5%) | |
Use of other medication | |||||||
Statin users | 2443 (43.6%) | 346 (60.7%)** | 270 (73.8%)** | 1825 (40.7%) | 607 (56.5%)** | 627 (64.1%)** | |
Anti-diabetic drug users | 1024 (18.3%) | 158 (27.7%)** | 92 (25.1%) | 780 (17.4%) | 277 (25.8%)** | 217 (22.2%)** | |
Anti-hypertensive drug users | 3868 (69.1%) | 540 (94.7%)** | 340 (92.9%)** | 2966 (66.1%) | 998 (92.9%)** | 784 (80.2%)** | |
NSAID users | 4806 (85.8%) | 487 (85.4%) | 343 (93.7%)** | 3800 (84.7%) | 935 (87.1%) | 901 (92.1%)** | |
Alpha-blocker users | 2509 (44.8%) | 320 (56.1%)** | 203 (55.5%)** | 2017 (45.0%) | 536 (49.9%) | 479 (49.0%) | |
Aspirin users | 623 (11.1%) | 91 (16.0%) | 174 (47.5%)** | 393 (8.8%) | 151 (14.1%)** | 344 (35.2%)** | |
Recorded diagnoses of: | |||||||
Atrial fibrillation | 404 (7.2%) | 303 (53.2%)** | 27 (7.4%) | 129 (2.9%) | 571 (53.2%)** | 34 (3.5%) | |
Thrombotic factors* | 198 (3.5%) | 93 (16.3%)** | 36 (9.8%) | 88 (2.0%) | 169 (15.7%)** | 70 (7.2%)** | |
Charlson Comorbidity Score | |||||||
0 | 3469 (61.9%) | 226 (39.6%)** | 127 (34.7%)** | 2955 (65.9%) | 449 (41.8%)** | 418 (42.7%)** | |
1 | 1093 (19.5%) | 147 (25.8%) | 113 (30.9%) | 822 (18.3%) | 272 (25.3%)** | 259 (26.5%)** | |
2 | 1039 (18.6%) | 197 (34.6%)** | 126 (34.4%)** | 708 (15.8%) | 353 (32.9%)** | 301 (30.8 %)** |
Risk of PCa death by pre-diagnostic use of warfarin and other anticoagulants
n of deaths | Age-adjusted | Multivariable-adjusted | |
---|---|---|---|
Warfarin compared to non-users | |||
None | 624 | Ref | Ref |
Any | 65 | 1.11 (0.85-1.44) | 1.15 (0.88-1.49) |
Amount of warfarin use | |||
≤200 DDD | 24 | 0.98 (0.65-1.48) | 0.97 (0.64-1.47) |
201-796 DDD | 18 | 1.09 (0.68-1.74) | 1.19 (0.74-1.91) |
>796 DDD | 23 | 1.31 (0.86-1.99) | 1.37 (0.90-2.09) |
Duration of warfarin use | |||
≤1 year | 20 | 0.91 (0.53-1.56) | 0.72 (0.42-1.24) |
2-4 years | 22 | 0.96 (0.57-1.61) | 0.87 (0.52-1.47) |
5 or more years | 23 | 1.33 (0.80-2.23) | 1.16 (0.69-1.94) |
Intensity of warfarin use | |||
≤114 DDD/year | 21 | 0.95 (0.56-1.62) | 0.79 (0.47-1.35) |
115-200 DDD/year | 24 | 1.09 (0.65-1.81) | 0.94 (0.57-1.57) |
>200 DDD/year | 20 | 1.10 (0.64-1.89) | 0.96 (0.56-1.65) |
Risk of PCa death by post-diagnostic anticoagulant use
n of deaths | Age-adjusted | Multivariable-adjusted | 1-year lag-time | 2-year lag-time | 3-year lag-time | |
---|---|---|---|---|---|---|
Warfarin compared to non-users | ||||||
None | 509 | Ref | Ref | Ref | Ref | Ref |
Any | 121 |
1.46 (1.12-1.90)
|
1.47 (1.13-1.93)
| 1.12 (0.85-1.48) | 1.12 (0.85-1.48) | 1.08 (0.83-1.41) |
Amount of warfarin use | ||||||
≤200 DDD | 63 |
2.47 (1.84-3.31)
|
2.50 (1.86-3.36)
|
1.45 (1.04-2.02)
| 1.34 (0.99-1.83) | 1.26 (0.94-1.70) |
200-667 DDD | 32 | 0.87 (0.53-1.42) | 0.88 (0.54-1.46) | 0.85 (0.52-1.41) | 0.76 (0.44-1.32) | 0.76 (0.43-1.36) |
>667 DDD | 26 | 0.97 (0.56-1.68) | 1.02 (0.59-1.78) | 1.05 (0.60-1.83) | 1.15 (0.67-1.97) | 1.04 (0.58-1.85) |
Duration of warfarin use | ||||||
≤1 year | 56 |
2.03 (1.47-2.81)
|
2.04 (1.47-2.83)
| 1.26 (0.89-1.78) | 1.25 (0.91-1.71) | 1.15 (0.85-1.57) |
2-4 years | 44 | 1.28 (0.88-1.87) | 1.30 (0.89-1.90) | 1.11 (0.73-1.69) | 0.87 (0.53-1.42) | 0.93 (0.56-1.54) |
5 or more years | 21 | 0.95 (0.49-1.85) | 1.05 (0.54-2.04) | 1.06 (0.56-1.99) | 1.37 (0.76-2.47) | 1.22 (0.66-2.26) |
Intensity of warfarin use | ||||||
≤128 DDD/year | 45 |
1.92 (1.34-2.74)
|
1.91 (1.34-2.74)
| 1.31 (0.91-1.88) | 1.35 (0.98-1.86) | 1.21 (0.89-1.66) |
128-200 DDD/year | 51 |
1.74 (1.24-2.45)
|
1.77 (1.25-2.50)
| 1.13 (0.74-1.74) | 0.93 (0.57-1.51) | 0.94 (0.57-1.56) |
>200 DDD/year | 25 | 0.73 (0.40-1.33) | 0.78 (0.43-1.43) | 0.99 (0.58-1.69) | 0.97 (0.56-1.69) | 0.99 (0.56-1.77) |
Warfarin compared to other anticoagulant drugs | ||||||
Non-warfarin anticoagulant users | 98 | Ref | Ref | Ref | Ref | Ref |
Warfarin users | 121 | 1.13 (0.79-1.61) | 1.01 (0.71-1.44) | 0.93 (0.64-1.35) | 1.02 (0.70-1.48) | 0.93 (0.65-1.33) |
Amount of warfarin use | ||||||
≤200 DDD | 63 |
1.85 (1.25-2.74)
|
1.63 (1.10-2.42)
| 1.15 (0.75-1.77) | 1.19 (0.78-1.80) | 1.06 (0.71-1.58) |
200-667 DDD | 32 | 0.65 (0.37-1.14) | 0.58 (0.33-1.01) | 0.68 (0.38-1.20) | 0.67 (0.36-1.25) | 0.64 (0.34-1.21) |
>667 DDD | 26 | 0.72 (0.39-1.33) | 0.67 (0.36-1.23) | 0.83 (0.45-1.55) | 1.02 (0.56-1.87) | 0.87 (0.46-1.64) |
Duration of warfarin use | ||||||
≤1 year | 56 | 1.52 (1.00-2.31) | 1.33 (0.88-2.02) | 1.00 (0.64-1.55) | 1.11 (0.73-1.68) | 0.97 (0.65-1.45) |
2-4 years | 44 | 0.96 (0.61-1.52) | 0.85 (0.54-1.34) | 0.88 (0.53-1.46) | 0.77 (0.44-1.35) | 0.78 (0.44-1.38) |
5 or more years | 21 | 0.71 (0.35-1.46) | 0.69 (0.34-1.40) | 0.84 (0.42-1.67) | 1.22 (0.64-2.33) | 1.02 (0.53-2.00) |
Intensity of warfarin use | ||||||
≤128 DDD/year | 45 | 1.44 (0.93-2.24) | 1.25 (0.80-1.95) | 1.04 (0.66-1.64) | 1.20 (0.78-1.83) | 1.02 (0.68-1.53) |
128-200 DDD/year | 51 | 1.31 (0.85-2.01) | 1.16 (0.75-1.78) | 0.90 (0.54-1.49) | 0.82 (0.47-1.44) | 0.79 (0.45-1.40) |
>200 DDD/year | 25 | 0.55 (0.29-1.05) |
0.51 (0.27-0.98)
| 0.79 (0.43-1.44) | 0.86 (0.46-1.60) | 0.83 (0.44-1.57) |