Introduction
Methods
Study cohort
Information on anticoagulant usage
Statistical analysis
Results
Population characteristics
Anticoagulant user status | ||||||
---|---|---|---|---|---|---|
No anticoagulation | Warfarina | LMWHa | Non-warfarin or LMWH anticoagulants | Total n of deaths | Median age at death | |
n of men in the study population | 42.708 | 17.826 | 12.326 | 8.595 | ||
Overall cancer mortality/10,000 person years n of cancer deaths | 75 | 54 | 81 | 46 | ||
Overall |
4,766 (11.2%)
| 1,549 (8.7%) |
1,733 (14.1%)
|
654 (7.6%)
|
8.033
|
72
|
Lung cancer | 1,404 (3.3%) | 380 (2.1%) | 351 (2.8%) | 213 (2.5%) | 1.739 | 71 |
Gastric cancer | 203 (0.7%) | 52 (0.3%) | 76 (0.6%) | 24 (0.3%) | 327 | 71 |
Colorectal cancer | 414 (1.0%) | 144 (0.8%) | 233 (1.9%) | 49 (0.6%) | 764 | 72 |
Central nervous system cancers | 112 (0.3%) | 32 (0.2%) | 27 (0.2%) | 21 (0.2%) | 182 | 69 |
Non-Hodgkin lymphomas | 125 (0.3%) | 64 (0.4%) | 65 (0.5%) | 18 (0.2%) | 244 | 74 |
Hepatic cancer | 292 (0.7%) | 79 (0.4%) | 67 (0.5%) | 34 (0.4%) | 441 | 71 |
Pancreatic cancer | 432(1.0%) | 118 (0.7%) | 195 (1.6%) | 45 (0.5%) | 733 | 71 |
Renal cancer | 124 (0.3%) | 51 (0.3%) | 72 (0.6%) | 20 (0.2%) | 239 | 72 |
Bladder cancer | 87 (0.2%) | 52 (0.3%) | 66 (0.5%) | 18 (0.2%) | 195 | 73 |
Recorded diagnoses of | ||||||
Pulmonary embolisms | 112 (0.3%) | 661 (3.7%) | 634 (5.1%) | 59 (0.7%) | ||
Venous thromboembolism | 23 (0.1%) | 205 (1.2%) | 233 (1.9%) | 12 (0.1%) | ||
Atrial fibrillation | 953 (2.2%) | 9,174 (51.5%) | 3,833 (31.1%) | 508 (0.6%) | ||
Charlson Comorbidity Score | ||||||
0 points | 24,979 (58.5%) | 6,354 (35.6%) | 4,133 (33.5%) | 3,879 (45.1%) | ||
1–2 points | 12,669 (29.7%) | 6,226 (34.9%) | 4,566 (37.0%) | 3,020 (35.1%) | ||
3 or more points | 5,060 (11.8%) | 5,246 (29.4%) | 3,627 (29.4%) | 1,696 (19.7%) | ||
Use of other medication | ||||||
Statin users | 16,307 (38.2%) | 11,613 (65.1%) | 7,827 (63.5%) | 7,060 (82.1%) | ||
Aspirin users | 4,218 (9.9%) | 3,666 (20.6%) | 2,542 (20.6%) | 4,266 (49.6%) | ||
NSAID users | 34,574 (80.1%) | 16,016 (89.8%) | 11,865 (96.3%) | 7,883 (91.7%) | ||
Antihypertensive drug users | 27,860 (65.2%) | 17,055 (95.7%) | 10,698 (86.8%) | 7,835 (91.2%) | ||
Antidiabetic drug users | 6,300 (14.8%) | 4,237 (23.8%) | 3,154 (25.6%) | 2,215 (25.8%) | ||
Body Mass Index (BMI)b | ||||||
< 27.6 | 3,442 (8.1%) | 1,078 (6.0%) | 958 (7.8%) | 604 (7.0%) | ||
≥ 27.6 | 2,780 (6.5%) | 1,603 (9.0%) | 1,265 (10.3%) | 700 (8.1%) |
Risk of cancer death by use of any anticoagulants
Risk of cancer death in relation to warfarin use
n of deaths | Multivariable-adjusted | 1-year lag-time | 2-year lag-time | 3-year lag-time | |
---|---|---|---|---|---|
Any anticoagulant compared to anticoagulant non-users | |||||
None | 4.766 | Ref. | Ref. | Ref. | Ref. |
Ever-users | 3.267 |
2.50 (2.37–2.64)
|
2.20 (2.08–2.32)
|
1.73 (1.64–1.83)
|
1.67 (1.57–1.77)
|
Amount of anticoagulant use | |||||
≤ 200 DDD | 1.348 |
2.28 (2.14–2.43)
|
1.94 (1.82–2.08)
|
1.52 (1.42–1.64)
|
1.54 (1.43–1.66)
|
200–1,100 DDD | 1.046 |
2.74 (2.54–2.96)
|
2.41 (2.23–2.61)
|
1.90 (1.74–2.06)
|
1.77 (1.62–1.93)
|
> 1,100 DDD | 873 |
2.84 (2.62–3.09)
|
2.64 (2.42–2.87)
|
2.06 (1.88–2.26)
|
1.87 (1.69–2.07)
|
Duration of anticoagulant use | |||||
≤ 2 year | 1.867 |
2.47 (2.33–2.62)
|
2.12 (1.99–2.25)
|
1.61 (1.51–1.72)
|
1.57 (1.47–1.68)
|
3–5 years | 663 |
2.64 (2.42–2.89)
|
2.38 (2.17–2.61)
|
1.91 (1.73–2.11)
|
1.78 (1.60–1.98)
|
6 or more years | 737 |
2.50 (2.29–2.74)
|
2.34 (2.13–2.56)
|
1.99 (1.80–2.19)
|
1.91 (1.72–2.11)
|
Intensity of anticoagulant use | |||||
≤ 100 DDD/year | 1.234 |
2.23 (2.09–2.38)
|
1.91 (1.78–2.05)
|
2.53 (1.42–1.65)
|
1.52 (1.40–1.64)
|
97–207 DDD/year | 929 |
2.50 (2.31–2.70)
|
2.16 (1.99–2.35)
|
1.78 (1.63–1.94)
|
1.78 (1.63–1.95)
|
> 207 DDD/year | 1.104 |
3.09 (2.87–3.34)
|
2.84 (2.62–3.06)
|
2.07 (1.90–2.25)
|
1.83 (1.67–2.01)
|
Warfarin compared to anticoagulant non-users | |||||
None | 4.766 | Ref. | Ref. | Ref. | Ref. |
Ever-users | 1.549 |
2.34 (2.20–2.48)
|
2.06 (1.94–2.19)
|
1.73 (1.63–1.85)
|
1.66 (1.55–1.77)
|
Amount of warfarin use | |||||
≤ 307 DDD | 713 |
2.61 (2.39–2.84)
|
2.25 (2.06–2.46)
|
1.74 (1.58–1.91)
|
1.71 (1.55–1.89)
|
307–1200 DDD | 482 |
2.29 (2.07–2.55)
|
2.19 (1.97–2.44)
|
1.85 (1.66–2.07)
|
1.76 (1.57–1.98)
|
> 1200 DDD | 354 |
2.04 (1.81–2.30)
|
2.07 (1.84–2.33)
|
1.81 (1.60–2.05)
|
1.70 (1.49–1.95)
|
Duration of warfarin use | |||||
≤ 2 year | 720 |
2.45 (2.25–2.67)
|
2.18 (1.99–2.38)
|
1.70 (1.55–1.87)
|
1.67 (1.51–1.84)
|
3–7 years | 504 |
2.37 (2.14–2.63)
|
2.23 (2.00–2.47)
|
1.83 (1.63–2.04)
|
1.67 (1.48–1.87)
|
8 or more years | 325 |
2.21 (1.95–2.50)
|
2.17 (1.91–2.46)
|
1.96 (1.72–2.24)
|
2.00 (1.74–2.30)
|
Intensity of warfarin use | |||||
≤ 120 DDD/year | 701 |
2.34 (2.14–2.55)
|
2.09 (1.90–2.29)
|
1.68 (1.52–1.87)
|
1.65 (1.49–1.84)
|
120–193 DDD/year | 446 |
1.75 (1.58–1.95)
|
1.77 (1.59–1.98)
|
1.56 (1.39–1.75)
|
1.58 (1.40–1.78)
|
> 193 DDD/year | 402 |
1.53 (1.37–1.70)
|
1.75 (1.58–1.95)
|
1.71 (1.54–1.91)
|
1.66 (1.48–1.86)
|
Warfarin compared to other anticoagulant drugs | |||||
Non-warfarin anticoagulant users | 1.718 | Ref. | Ref. | Ref. | Ref. |
Warfarin users | 1.549 |
0.45 (0.41–0.50)
| 1.00 (0.91–1.09) | 1.09 (0.99–1.21) | 1.03 (0.92–1.14) |
Amount of warfarin use | |||||
≤ 307 DDD | 713 |
0.68 (0.59–0.78)
|
1.23 (1.07–1.40)
| 1.12 (0.96–1.31) | 1.13 (0.96–1.33) |
307–1200 DDD | 482 |
0.39 (0.33–0.45)
| 0.94 (0.83–1.07) | 1.10 (0.96–1.26) | 0.99 (0.86–1.15) |
> 1200 DDD | 354 |
0.36 (0.31–0.43)
| 0.88 (0.77–1.01) | 1.07 (0.92–1.24) | 0.98 (0.83–1.15) |
Duration of warfarin use | |||||
≤ 2 year | 720 |
0.58 (0.50–0.66)
|
1.17 (1.03–1.33)
| 1.11 (0.96–1.28) | 1.09 (0.93–1.27) |
3–7 years | 504 |
0.40 (0.34–0.46)
| 0.92 (0.81–1.04) | 1.05 (0.92–1.20) | 0.90 (0.78–1.04) |
8 or more years | 325 |
0.40 (0.34–0.47)
| 0.92 (0.79–1.06) | 1.14 (0.98–1.33) | 1.17 (0.99–1.39) |
Intensity of warfarin use | |||||
≤ 120 DDD/year | 701 |
0.71 (0.62–0.81)
|
1.23 (1.07–1.40)
| 1.14 (0.98–1.33) | 1.04 (0.88–1.24) |
120–193 DDD/year | 446 |
0.42 (0.36–0.49)
| 0.99 (0.86–1.13) | 1.05 (0.91–1.22) | 0.99 (0.84–1.17) |
> 193 DDD/year | 402 |
0.31 (0.27–0.37)
|
0.86 (0.76–0.98)
| 1.09 (0.96–1.25) | 1.04 (0.91–1.20) |
LMWH compared to other anticoagulant drugs | |||||
Non-LMWH anticoagulant users | 1.534 | Ref. | Ref. | Ref. | Ref. |
LMWH users | 1.733 |
2.04 (1.90–2.20)
|
1.57 (1.45–1.70)
| 1.02 (0.93–1.12) |
0.86 (0.77–0.95)
|
Amount of warfarin use | |||||
≤ 40 DDD | 497 | 1.09 (0.98–1.20) | 0.99 (0.89–1.11) |
0.81 (0.72–0.91)
|
0.73 (0.63–0.83)
|
40–80 DDD | 276 |
1.59 (1.40–1.82)
|
1.28 (1.10–1.48)
| 0.95 (0.79–1.13) | 0.90 (0.74–1.10) |
> 80 DDD | 960 |
4.73 (4.34–5.15)
|
3.38 (3.06–3.74)
|
1.70 (1.48–1.96)
|
1.23 (1.02–1.47)
|
Duration of warfarin use | |||||
≤ 1 year | 1.173 |
1.80 (1.66–1.94)
|
1.46 (1.34–1.59)
| 0.96 (0.87–1.06) |
0.83 (0.74–0.93)
|
2 or more years | 560 |
3.00 (2.71–3.32)
|
2.00 (1.77–2.27)
|
1.29 (1.09–1.52)
| 0.98 (0.79–1.21) |
Intensity of warfarin use | |||||
≤ 40 DDD/year | 580 |
1.12 (1.01–1.23)
| 1.01 (0.91–1.11) |
0.82 (0.73–0.92)
|
0.75 (0.65–0.85)
|
40–60 DDD/year | 198 |
1.66 (1.43–1.93)
|
1.35 (1.14–1.61)
| 1.07 (0.87–1.32) | 0.97 (0.77–1.23) |
> 60 DDD/year | 955 |
4.83 (4.43–5.26)
|
3.40 (3.07–3.75)
|
1.62 (1.41–1.87)
| 1.15 (0.96–1.38) |
n of deaths | Multivariable-adjusted | 1-year lag-time | 2-year lag-time | 3-year lag-time | |
---|---|---|---|---|---|
Any anticoagulant compared to anticoagulant non-users | |||||
All cancers | |||||
Non-user | 4.766 | Ref. | Ref. | Ref. | Ref. |
Ever-user | 3.267 |
2.50 (2.37–2.64)
|
2.20 (2.08–2.32)
|
1.73 (1.64–1.83)
|
1.67 (1–57–1.77)
|
Cancer type | |||||
Lung cancer | 799/1,404a |
2.19 (1.97–2.42)
|
1.89 (1.70–2.10)
|
1.55 (1.39–1.74)
|
1.53 (1.36–1.71)
|
Gastric cancer | 124/203a |
3.03 (2.33–3.96)
|
2.93 (2.24–3.85)
|
2.13 (2.60–2.84)
|
2.00 (1.48–2.70)
|
Colorectal cancer | 350/414a |
3.51 (2.96–4.16)
|
3.01 (2.53–3.58)
|
2.15 (1.80–2.58)
|
1.80 (1.49–2.18)
|
Central nervous system cancers | 70/112a |
3.23 (2.25–4.64)
|
3.02 (2.09–4.36)
|
1.59 (1.06–2.39)
|
1.28 (0.83–1.99)
|
Non-Hodgkin lymphomas | 119/125a |
2.91 (2.16–3.93)
|
2.53 (1.87–3.42)
|
1.97 (1.44–2.68)
|
1.69 (1.23–2.33)
|
Hepatic cancer | 149/292a |
1.64 (1.30–2.06)
|
1.43 (1.13–1.82)
|
1.32 (1.03–1.69)
|
1.37 (1.06–1.78)
|
Pancreatic cancer | 301/431a |
2.90 (2.44–3.46)
|
2.10 (1.75–2.52)
|
1.48 (1.22–1.80)
|
1.51 (1.23–1.84)
|
Kidney cancer | 115/124a |
3.08 (2.28–4.17)
|
2.35 (1.73–3.19)
|
1.75 (1.27–2.41)
|
1.75 (1.26–2.43)
|
Bladder cancer | 108/87a |
4.99 (3.58–6.96)
|
4.44 (3.19–6.20)
|
2.87 (2.04–4.04)
|
2.67 (1.89–3.77)
|
Warfarin compared to anticoagulant non-users | |||||
All cancers | |||||
No anticoagulant use | 4.766 | Ref. | Ref. | Ref. | Ref. |
Warfarin ever-use | 1.549 |
2.34 (2.20–2.48)
|
2.06 (1.94–2.19)
|
1.73 (1.63–1.85)
|
1.66 (1.55–1.77)
|
Cancer type | |||||
Lung cancer | 380/1,404b |
2.01 (1.79–2.26)
|
1.74 (1.54–1.97)
|
1.51 (1.33–1.72)
|
1.40 (1.22–1.60)
|
Gastric cancer | 52/203b |
2.89 (2.14–3.90)
|
2.56 (1.87–3.51)
|
2.02 (1.45–2.82)
|
1.85 (1.30–2.63)
|
Colorectal cancer | 144/414b |
3.10 (2.56–3.76)
|
2.68 (2.20–3.26)
|
2.03 (1.65–2.49)
|
1.82 (1.47–2.25)
|
Central nervous system cancers | 32/112b |
2.68 (1.77–4.05)
|
2.43 (1.58–3.74)
| 1.39 (0.87–2.23) | 1.02 (0.61–1.73) |
Non-Hodgkin lymphomas | 64/125b |
2.73 (1.96–3.81)
|
2.48 (1.78–3.46)
|
2.04 (1.45–2.86)
|
1.88 (1.32–2.67)
|
Hepatic cancer | 79/292b |
1.47 (1.13–1.91)
|
1.51 (1.16–1.96)
|
1.42 (1.08–1.87)
|
1.53 (1.15–2.02)
|
Pancreatic cancer | 118/431b |
2.47 (2.02–3.01)
|
1.80 (1.46–2.22)
|
1.55 (1.25–1.93)
|
1.54 (1.22–1.93)
|
Renal cancer | 51/124b |
2.73 (1.95–3.83)
|
2.12 (1.50–2.99)
|
1.57 (1.09–2.25)
| 1.40 (0.95–2.06) |
Bladder cancer | 52/87b |
5.29 (3.69–7.60)
|
4.45 (3.09–6.40)
|
2.91 (2.00–4.24)
|
2.62 (1.78–3.88)
|
Warfarin compared to other anticoagulant drugs | |||||
All cancers | |||||
Non-warfarin anticoagulant users | 1.718 | Ref. | Ref. | Ref. | Ref. |
Warfarin users | 1.549 |
0.45 (0.41–0.50)
| 1.00 (0.91–1.09) | 1.09 (0.99–1.21) | 1.03 (0.92–1.14) |
Cancer type | |||||
Lung cancer | 380/419c |
0.63 (0.52–0.75)
| 1.09 (0.91–1.30) | 1.13 (0.93–1.38) | 1.00 (0.81–1.24) |
Gastric cancer | 52/72c |
0.35 (0.20–0.61)
| 1.11 (0.70–1.77) | 1.29 (0.78–2.12) | 0.86 (0.49–1.51) |
Colorectal cancer | 144/206c |
0.37 (0.27–0.51)
| 0.86 (0.65–1.15) | 1.02 (0.74–1.40) | 1.10 (0.77–1.56) |
Central nervous system cancers | 32/38c |
0.43 (0.23–0.83)
| 1.40 (0.77–2.55) | 1.08 (0.52–2.26) | 1.00 (0.44–2.27) |
Non-Hodgkin lymphomas | 64/55c |
0.48 (0.29–0.78)
|
1.79 (1.14–2.82)
|
1.75 (1.07–2.87)
| 1.64 (0.96–2.81) |
Hepatic cancer | 70/79c |
0.45 (0.29–0.69)
| 0.82 (0.53–1.25) | 0.97 (0.62–1.53) | 1.06 (0.65–1.71) |
Pancreatic cancer | 118/183c |
0.34 (0.23–0.48)
| 0.79 (0.57–1.10) | 1.26 (0.88–1.80) | 1.16 (0.79–1.69) |
Renal cancer | 51/64c |
0.31 (0.18–0.56)
| 0.71 (0.43–1.18) | 0.77 (0.43–1.36) | 0.60 (0.32–1.14) |
Bladder cancer | 52/56c |
0.41 (0.23–0.72)
| 0.98 (0.59–1.63) | 1.16 (0.66–2.03) | 1.40 (0.79–2.51) |
LMWH compared to other anticoagulants | |||||
All cancers | |||||
Non-LMWH anticoagulants | 1.534 | Ref. | Ref. | Ref. | Ref. |
LMWH | 1.733 |
2.04 (1.90–2.20)
|
1.57 (1.45–1.70)
| 1.02 (0.93–1.12) |
0.86 (0.77–0.95)
|
Cancer type | |||||
Lung cancer | 351/448d |
1.46 (1.26–1.69)
| 1.10 (0.93–1.30) |
0.67 (0.54–0.82)
| 0.61 (0.48–0.77) |
Gastric cancer | 48/76d |
3.39 (2.30–4.98)
|
3.19 (2.14–4.75)
| 1.31 (0.82–2.09) | 1.16 (0.69–1.96) |
Colorectal cancer | 233/117d |
3.60 (2.84–4.56)
|
2.75 (2.15–3.50)
|
1.70 (1.29–2.23)
| 1.06 (0.77–1.45) |
Central nervous system cancers | 27/43d | 1.10 (0.66–1.84) | 0.73 (0.41–1.31) | 0.65 (0.30–1.40) | 0.76 (0.32–1.79) |
Non-Hodgkin lymphomas | 65/54d |
2.38 (1.62–3.50)
|
2.17 (1.44–3.26)
|
1.87 (1.20–2.94)
|
1.79 (1.09–2.93)
|
Hepatic cancer | 67/82d |
1.46 (1.04–2.05)
| 0.84 (0.56–1.25) |
0.43 (0.25–0.73)
|
0.45 (0.25–0.80)
|
Pancreatic cancer | 195/106d |
3.57 (2.78–4.58)
|
1.91 (1.46–2.50)
| 1.05 (0.76–1.46) | 0.81 (0.56–1.18) |
Renal cancer | 72/43d |
3.21 (2.14–4.81)
|
2.81 (1.83–4.32)
|
1.72 (1.07–2.77)
| 1.46 (0.87–2.44) |
Bladder cancer | 66/42d |
2.80 (1.85–4.25)
|
1.78 (1.16–2.73)
| 0.95 (0.57–1.59) | 0.67 (0.37–1.21) |