Table 1. Efficacy and safety of direct oral anticoagulants for treatment of cancer-associated venous thromboembolism.
| Studies 81– 84 | Intervention | Control | Primary outcome | Symptomatic VTE | Bleeding | Mortality |
|---|---|---|---|---|---|---|
| HOKUSAI
VTE Cancer (n = 1050) |
Edoxaban a | Dalteparin b | VTE or MB at 12
months 12.8% vs. 13.5% HR 0.97 (0.70–1.36) |
7.9% vs. 11.3%
HR 0.71 (0.48–1.06) |
MB: 6.9% vs. 4.0%
HR 1.77 (1.03–3.04) Major GI bleeding: 3.8% vs. 1.1% |
39.5% vs. 36.6%
HR 1.12 (0.92–1.37) |
| SELECT-D
c
(n = 406) |
Rivaroxaban d | Dalteparin b | VTE at 6 months | 4% vs. 11%
HR 0.43 (0.19–0.99) |
6% vs. 4%
HR 1.83 (0.68–4.96) Major GI bleeding: 3.9% vs. 2.0% |
25% vs. 30% |
| ADAM VTE
e
(n = 300) |
Apixaban f | Dalteparin b | MB at 6 months | 0.7% vs. 6.3%
HR 0.09 (0.013–0.78) |
0% vs. 1.4%
Major GI bleeding: none |
16% vs. 11% |
| CARAVAGGIO
(n = 1170) |
Apixabanf | Dalteparinb | VTE at 6 months | 5.6% vs. 7.9%
HR 0.63 (0.37–1.07) |
3.8 vs 4.0%
HR 0.82 (0.40–1.69) Major GI bleeding: 1.9% vs. 1.7% HR 1.05 (0.44–2.50) |
23.4% vs. 26.4%
HR 0.82 (0.62–1.09) |
GI, gastrointestinal; HR, hazard ratio (with 95% confidence interval in parentheses); MB, major bleeding; n, number of patients who underwent randomization; VTE, (objectively diagnosed) venous thromboembolism.
aLead-in of therapeutic low-molecular-weight heparin for at least 5 days followed by edoxaban 60 mg once daily or 30 mg once daily in patients with creatinine clearance of 30 to 50 mL/min, body weight of less than 60 kg, or receiving concomitant strong P-glycoprotein inhibitors.
b200 IU/kg daily for 30 days followed by 150 IU/kg daily thereafter.
cBecause of slow recruitment, sample size was reduced to 406 from planned 530 patients.
d15 mg twice daily for 21 days followed by 20 mg once daily thereafter.
eWith a sample size of 300 patients, this study was powered to detect only large (>78%) reductions in the primary outcome. Proportions of patients with upper GI cancers were generally low in these trials: HOKUSAI VTE Cancer (5.1%), SELECT‐D (7.3%), ADAM VTE (3.6%) and CARAVAGGIO (4.6%).
f10 mg twice daily for 7 days followed by 5 mg twice daily thereafter.