Copyright
©The Author(s) 2019.
World J Gastrointest Oncol. Oct 15, 2019; 11(10): 866-876
Published online Oct 15, 2019. doi: 10.4251/wjgo.v11.i10.866
Published online Oct 15, 2019. doi: 10.4251/wjgo.v11.i10.866
Table 1 Clinical trials for low molecular weight heparin primary efficacy and secondary safety compared to vitamin K antagonist
Study (yr) | InterventionLMWH | Reported efficacy (rVTE) (%) | Reported safety (MB) (%) | Control VKA | Reported efficacy (rVTE) (%) | Reported safety (MB) (%) | Mortality Benefit at 12 mo |
CLOT (2003)[3] | Dalteparin | 9.0 | 6.0 | Warfarin | 17.0 | 4.0 | HR 0.50, 95%CI: 0.27-0.95 |
LITE (2006)[4] | Tinzaparin | 7.0 | 0.0 | Warfarin | 16.0 | 2.1 | NS |
CANTHANOX (2002)[5] | Enoxaparin | 10.5 | 5.0 | Warfarin | 21.1 | 12.0 | NS |
ONCENOX (2006)[6] | Enoxaparin | 6.3 | 6.5 | Warfarin | 10.0 | 2.1 | NS |
CATCH (2015)[7] | Tinzaparin | 7.2 | 2.6 | Tinzaparin + Warfarin | 10.5 | 2.4 | NS |
Table 2 Clinical trials for direct oral anticoagulants reported recurrent venous thromboembolism and reported mayor bleed outcomes compared to cancer subgroup
Study | Intervention DOAC | Control | Reported efficacy (rVTE) (%) | Cancer subgroup efficacy (%) | Reported safety (MB) (%) | Cancer subgroup safety (%) | Yr |
AMPLIFY[17] | Apixaban | Enoxaparin + Warfarin | 2.30 | 3.70 | 0.6 | 2.3 | 2013 |
AMPLIFY-EXT[18] | Apixaban | Placebo | 4.00 | NA | 0.2 | NA | 2013 |
RE-COVER[19] | Dabigatran | Heparin + Warfarin | 3.10 | 3.10 | 1.60 | 4.20 | 2009 |
RE-COVER II[20] | Dabigatran | Heparin + Warfarin | 2.30 | 2.40 | 1.20 | < 1 | 2013 |
RE-MEDY[21] | Dabigatran | Warfarin | 1.80 | 3.30 | 0.90 | NA | 2013 |
RE-SONATE[21] | Dabigatran | Placebo | 0.40 | NA | 0.30 | NA | 2013 |
HOKUSAI-VTE[22] | Edoxaban | Warfarin | 3.20 | 3.70 | 1.40 | 4.50 | 2013 |
EINSTEIN-Choice[25] | Rivaroxaban | Aspirin | 1.50 | NA | 0.5 | NA | 2017 |
EINSTEIN-DVT[23] | Rivaroxaban | Enoxaparin+ Warfarin | 2.10 | 3.40 | 0.8 | 14.4 | 2010 |
EINSTEIN-EXT[26] | Rivaroxaban | Placebo | 1.30 | 2.10 | 0.7 | 12.3 | 2016 |
EINSTEIN-PE[24] | Rivaroxaban | Enoxaparin+ Warfarin | 2.10 | 2 | 1.1 | 12.3 | 2012 |
Table 3 Baseline characteristics of the study population
Baseline characteristics | LMWH (%) | DOACs (%) | Apixaban (%) | Rivaroxaban (%) |
N (%) | 40 | 66 | 29 (44) | 37 (56) |
Age at cancer diagnosis (median years) | 66 | 67 | 68 | 65 |
(range) | 37-80 | 37-83 | 43-83 | 37-79 |
Age at VTE event (median years) | 66 | 68 | 68 | 65 |
(range) | 40-80 | 37-83 | 43-83 | 37-79 |
Weight (median kg) | 71.0 | 73.0 | 69.5 | 77.0 |
(range) | 42-130 | 42-168 | 42-168 | 56-130 |
Gender (Male) | 18 (45) | 41 (62) | 17 (59) | 24 (65) |
Race (white) | 32 (80) | 52 (79) | 21 (72) | 31 (84) |
Current smoker | 10 (25) | 12 (18) | 6 (21) | 6 (15) |
Antiplatelet therapy | 5 (12.5) | 8 (12) | 5 (17) | 3 (8) |
Prior treated VTE | 2 (5) | 7 (11) | 2 (7) | 5 (13) |
Cancer diagnosis | ||||
Pancreas | 15 (37.5) | 28 (42) | 14 (50) | 14 (38) |
Colon | 8 (20) | 18 (27) | 8 (25) | 10 (27) |
Rectal | 2 (5) | 5 (8) | 1 (3.5) | 4 (11) |
NET | 3 (7.5) | 4 (6) | 1 (3.5) | 3 (8) |
Gastric | 4 (10) | 3 (5) | 1 (3.5) | 2 (5) |
Esophageal | 0 | 3 (5) | 1 (3.5) | 2 (5) |
Appendix | 1 (2.5) | 3 (5) | 2 (7) | 1 (3) |
Biliary | 3 (7.5) | 1 (1) | 1 (3.5) | 0 |
GEJ | 1 (2.5) | 1 (1) | 0 | 1 (3) |
HCC | 3 (7.5) | 0 | 0 | 0 |
Stage at VTE diagnosis | ||||
I | 1 (2.5) | 1 (1) | 1 (3.5) | 0 |
II | 7 (17.5) | 7 (11) | 3 (10.75) | 4 (10) |
III | 3 (7.5) | 12 (19) | 3 (10.75) | 9 (25) |
IV | 29 (72.5) | 46 (69) | 22 (75) | 24 (65) |
Prior chemotherapy | 24 (40) | 24 (36) | 11 (38) | 13 (35) |
Current chemotherapy | 24 (40) | 29 (47) | 18 (62) | 13 (35) |
VTE diagnosis | ||||
PE/DVT | 11 (27.5) | 8 (12) | 5 (17) | 3 (8) |
PE | 7 (17.5) | 8 (12) | 2 (7) | 6 (16) |
DVT | 22 (55) | 50 (75) | 22 (75) | 28 (76) |
Identifiable risk factor | 10 (16) | 5 (17) | 5 (14) | |
Recent surgery/Hospitalization | 2 (5) | 4 (6) | 3 (10) | 1 (3) |
Central venous catheter | 2 (5) | 6 (9) | 2 (7) | 4 (11) |
Khorana score | ||||
Low | 11 (27.5) | 19 (28) | 7 (24) | 12 (32) |
Intermediate | 18 (45) | 25 (38) | 11 (38) | 14 (38) |
High | 11 (27.5) | 22 (34) | 11 (38) | 11 (30) |
Therapy completion | 25 (62.5) | 43 (65) | 20 (69) | 23 (62) |
Anticoagulation length (median mo) | 4 | 6.5 | 8 | 6 |
(range) | 1-33 | 0.3-40 | 2-29 | 0.3-40 |
Table 4 Clinical risk factors of a primary or secondary outcome for all anticoagulation therapies
Clinical risk factor | Odds ratio | 95%CI | Significance level |
Active treatment | 5.1 | 1.3-19.3 | P = 0.0167 |
Khorana score high | 5.5 | 1.7-17.1 | P = 0.0033 |
Active smoker | 6.7 | 2.1-21.0 | P = 0.0012 |
Pancreatic cancer | 6.8 | 1.9-23.2 | P = 0.0023 |
Stage IV | 9.9 | 1.2-79.1 | P = 0.0306 |
Death after an event | 17.4 | 4.7-63.4 | P < 0.0001 |
- Citation: Recio-Boiles A, Veeravelli S, Vondrak J, Babiker HM, Scott AJ, Shroff RT, Patel H, Elquza E, McBride A. Evaluation of the safety and effectiveness of direct oral anticoagulants and low molecular weight heparin in gastrointestinal cancer-associated venous thromboembolism. World J Gastrointest Oncol 2019; 11(10): 866-876
- URL: https://www.wjgnet.com/1948-5204/full/v11/i10/866.htm
- DOI: https://dx.doi.org/10.4251/wjgo.v11.i10.866