Table 3.
Association of Anticoagulant Use to Treat Cancer-Associated (CA)-Venous Thromboembolism (VTE) with Hospitalized Bleeding
| Comparison* | N | Events | Person-Years | Model 1† | Model 2 | Model 3 | Model 4 |
|---|---|---|---|---|---|---|---|
| All Cancer | |||||||
| Warfarin (reference) | 6,951 | 309 | 6,556.3 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 3,183 | 111 | 2,278.9 | 0.91 (0.73–1.13) | 0.86 (0.69–1.08) | 0.87 (0.69–1.10) | 0.88 (0.69–1.11) |
| Rivaroxaban | 2,895 | 106 | 2,166.7 | 0.92 (0.74–1.15) | 0.88 (0.70–1.10) | 0.88 (0.70, 1.12) | 0.88 (0.70–1.12) |
| Warfarin (reference) | 14,833 | 716 | 17,724.7 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| LMWH | 8,803 | 373 | 7,184.4 | 1.10 (0.97–1.24) | 1.13 (0.99–1.29) | 0.97 (0.84–1.12) | 0.98 (0.85–1.13) |
| LMWH (reference) | 5,205 | 209 | 3401.6 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 3,183 | 111 | 2,278.9 | 0.82 (0.65–1.03) | 0.78 (0.63–1.01) | 0.86 (0.66–1.13) | 0.86 (0.66–1.12) |
| Rivaroxaban | 2,895 | 106 | 2,166.7 | 0.84 (0.67–1.06) | 0.82 (0.64–1.04) | 0.86 (0.65–1.13) | 0.86 (0.65–1.13) |
| Chemotherapy Treated Cancer | |||||||
| Warfarin (reference) | 2,912 | 144 | 2,389.9 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 1,373 | 56 | 848.6 | 0.97 (0.71–1.33) | 0.98 (0.71–1.35) | 0.95 (0.68–1.33) | 0.95 (0.68–1.34) |
| Rivaroxaban | 1,281 | 54 | 819.9 | 0.98 (0.72–1.34) | 0.98 (0.71–1.36) | 0.94 (0.67–1.32) | 0.94 (0.67 −1.32) |
| Warfarin (reference) | 6,750 | 368 | 6,861.1 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| LMWH | 6,420 | 290 | 5,118.7 | 0.95 (0.81–1.11) | 0.99 (0.84–1.15) | 0.92 (0.78–1.09) | 0.93 (0.78–1.10) |
| LMWH (reference) | 3,778 | 157 | 2453.4 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 1,373 | 56 | 848.6 | 0.99 (0.73–1.35) | 1.01 (0.74–1.38) | 1.05 (0.75–1.47) | 1.05 (0.75–1.47) |
| Rivaroxaban | 1,281 | 54 | 819.9 | 1.01 (0.74–1.37) | 1.03 (0.75–1.41) | 1.05 (0.74 −1.47) | 1.04 (0.74–1.47) |
| Lung Cancer | |||||||
| Warfarin (reference) | 871 | 35 | 651.1 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 409 | 9 | 200.5 | 0.68 (0.32–1.41) | 0.76 (0.31–1.46) | 0.73 (0.32–1.67) | 0.73 (0.32–1.67) |
| Rivaroxaban | 379 | 9 | 190.4 | 0.72 (0.34–1.49) | 0.71 (0.33–1.53) | 0.76 (0.33–1.74) | 0.76 (0.33–1.74) |
| Warfarin (reference) | 2,015 | 98 | 1,630.3 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| LMWH | 1,494 | 58 | 862.6 | 0.99 (0.71–1.37) | 0.98 (0.70–1.37) | 0.89 (0.62–1.28) | 0.89 (0.62–1.28) |
| LMWH (reference) | 880 | 35 | 493.9 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 409 | 9 | 200.5 | 0.57 (0.27–1.18) | 0.56 (0.26–1.19) | 0.85 (0.38–1.90) | 0.86 (0.39–1.92) |
| Rivaroxaban | 379 | 9 | 190.4 | 0.61 (0.29–1.26) | 0.59 (0.28–1.26) | 0.83 (0.37–1.85) | 0.83 (0.37–1.86) |
| Breast Cancer | |||||||
| Warfarin (reference) | 1,113 | 37 | 1,203.9 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 568 | 20 | 445.1 | 1.30 (0.75–2.25) | 1.24 (0.70–2.20) | 1.29 (0.72–2.31) | 1.35 (0.76–2.42) |
| Rivaroxaban | 518 | 19 | 421.0 | 1.32 (0.76–2.30) | 1.27 (0.71–2.26) | 1.32 (0.73–2.39) | 1.38 (0.77–2.49) |
| Warfarin (reference) | 2,330 | 91 | 3,272.9 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| LMWH | 1,004 | 26 | 1,047.6 | 0.83 (0.53–1.28) | 0.88 (0.56–1.37) | 0.70 (0.43–1.15) | 0.71 (0.43–1.16) |
| LMWH (reference) | 602 | 13 | 467.2 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 568 | 20 | 445.1 | 1.57 (0.78–3.16) | 1.37 (0.67–2.80) | 1.61 (0.71–3.65) | 1.67 (0.73–3.83) |
| Rivaroxaban | 518 | 19 | 421.0 | 1.61 (0.80–3.26) | 1.41 (0.69–2.91) | 1.55 (0.68–3.52) | 1.60 (0.70–3.68) |
| Colon Cancer | |||||||
| Warfarin (reference) | 686 | 40 | 631.9 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 304 | 16 | 217.1 | 1.05 (0.59–1.88) | 1.09 (0.60–1.99) | 0.99 (0.52–1.88) | 1.00 (0.53–1.90) |
| Rivaroxaban | 280 | 15 | 209.7 | 1.03 (0.57–1.87) | 1.07 (0.58–1.98) | 0.95 (0.50–1.83) | 0.97 (0.50–1.85) |
| Warfarin (reference) | 1,460 | 78 | 1,800.5 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| LMWH | 812 | 31 | 738.8 | 0.88 (0.58–1.33) | 0.88 (0.58–1.35) | 0.86 (0.55–1.34) | 0.86 (0.55–1.35) |
| LMWH (reference) | 496 | 15 | 372.3 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 304 | 16 | 217.1 | 1.81 (0.89–3.66) | 1.72 (0.83–3.57) | 1.46 (0.67–3.17) | 1.49 (0.69–3.23) |
| Rivaroxaban | 280 | 15 | 209.7 | 1.77 (0.87–3.62) | 1.72 (0.82–3.58) | 1.50 (0.69–3.28) | 1.52 (0.70–3.34) |
| Upper Gastrointestinal | |||||||
| Warfarin (reference) | 200 | 10 | 152.4 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 81 | 10 | 47.4 | 2.88 (1.20–6.93) | 3.09 (1.23–7.73) | 2.68 (0.95–7.55) | 2.69 (0.95–7.62) |
| Rivaroxaban | 79 | 10 | 47.0 | 2.91 (1.21–7.01) | 3.11 (1.24–7.78) | 2.63 (0.94–7.36) | 3.64 (0.94–7.41) |
| Warfarin (reference) | 408 | 24 | 364.5 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| LMWH | 386 | 22 | 236.3 | 1.20 (0.67–2.14) | 1.16 (0.64–2.10) | 1.09 (0.58–2.06) | 1.11 (0.59–2.10) |
| LMWH (reference) | 210 | 12 | 110.6 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 81 | 10 | 47.4 | 2.10 (0.91–4.87) | 2.28 (0.97–5.39) | 2.42 (0.95–6.20) | 2.36 (0.92–6.07) |
| Rivaroxaban | 79 | 10 | 47.0 | 2.14 (0.92–4.96) | 2.30 (0.98–5.43) | 2.27 (0.89–5.82) | 2.21 (0.86–5.70) |
| Prostate Cancer | |||||||
| Warfarin (reference) | 889 | 52 | 947.2 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 382 | 9 | 344.7 | 0.42 (0.21–0.86) | 0.38 (0.19–0.79) | 0.41 (0.19–0.86) | 0.40 (0.19–0.84) |
| Rivaroxaban | 332 | 7 | 326.5 | 0.36 (0.16–0.79) | 0.33 (0.15–0.73) | 0.36 (0.16–0.81) | 0.35 (0.15–0.79) |
| Warfarin (reference) | 1,794 | 99 | 2,562.3 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| LMWH | 362 | 22 | 336.9 | 1.44 (0.91–2.29) | 1.40 (0.87–2.24) | 1.00 (0.59–1.69) | 0.98 (0.58–1.66) |
| LMWH (reference) | 233 | 16 | 162.8 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 382 | 9 | 344.7 | 0.29 (0.13–0.65) | 0.30 (0.13–0.68) | 0.37 (0.15–0.93) | 0.37 (0.15–0.93) |
| Rivaroxaban | 332 | 7 | 326.5 | 0.24 (0.10–0.60) | 0.25 (0.10–0.62) | 0.31 (0.12–0.83) | 0.31 (0.12–0.83) |
| Hematologic Cancer | |||||||
| Warfarin (reference) | 822 | 39 | 821.0 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 367 | 13 | 275.2 | 0.85 (0.45–1.60) | 0.68 (0.36–1.31) | 0.71 (0.36–1.39) | 0.71 (0.36–1.39) |
| Rivaroxaban | 334 | 13 | 264.6 | 0.91 (0.48–1.70) | 0.74 (0.38–1.41) | 0.80 (0.41–1.56) | 0.80 (0.41–1.57) |
| Warfarin (reference) | 1,851 | 81 | 2,509.9 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| LMWH | 1,230 | 51 | 1,360.9 | 1.05 (0.74–1.50) | 1.01 (0.70–1.46) | 1.04 (0.70–1.56) | 1.05 (0.70–1.57) |
| LMWH (reference) | 740 | 27 | 626.1 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| DOAC | 367 | 13 | 275.2 | 0.99 (0.51–1.92) | 0.96 (0.49–1.89) | 0.88 (0.41–1.90) | 0.88 (0.41–1.90) |
| Rivaroxaban | 334 | 13 | 264.6 | 1.07 (0.55 −2.07) | 1.04 (0.53–2.04) | 1.00 (0.46–2.16) | 1.01 (0.47–2.17) |
*
Comparisons between any agent and DOACs restricted to after 11/2/2012 (initial approval of first DOAC to treat VTE)
†
Models:Model 1: No adjustment, Model 2: Adjusted for age, sex, year, Model 3: Adjusted for Model 2 + high dimension propensity score, Model 4: Adjusted for Model 3 + frailty