Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2019; 11(10): 866-876
Published online Oct 15, 2019. doi: 10.4251/wjgo.v11.i10.866
Evaluation of the safety and effectiveness of direct oral anticoagulants and low molecular weight heparin in gastrointestinal cancer-associated venous thromboembolism
Alejandro Recio-Boiles, Sumana Veeravelli, Jessica Vondrak, Hani M Babiker, Aaron J Scott, Rachna T Shroff, Hitendra Patel, Emad Elquza, Ali McBride
Alejandro Recio-Boiles, Hani M Babiker, Aaron J Scott, Rachna T Shroff, Emad Elquza, Department of Medicine, Hematology and Medical Oncology, University of Arizona Cancer Center, Tucson, AZ 85724, United States
Sumana Veeravelli, Jessica Vondrak, Department of Medicine, Internal Medicine Residency Program, University of Arizona, Tucson, AZ 85725, United States
Hitendra Patel, UC San Diego Health Moores Cancer Center, La Jolla, CA 92093, United States
Ali McBride, University of Arizona College of Pharmacy, Tucson, AZ 85725, United States
Author contributions: Recio-Boiles A, Patel H, Elquza E, and McBride A designed and drafted the study concept. Recio-Boiles A, Vondrak J, and Veeravelli S collected the data. Recio-Boiles A, Elquza E, and McBride A performed data analysis and interpretation. Recio-Boiles A, Babiker HM, Scott AJ, Shroff RT, Elquza E, and McBride A contributed to writing, revising and editing the manuscript. All authors helped to perform the research, revision of the manuscript and have approved the final version.
Institutional review board statement: This study has a statement on ethics approval by the Institutional Review Board of University of Arizona Cancer Center, which is a part of the University of Arizona The Human Subjects Protection Program.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Alejandro Recio-Boiles, MD, Assistant Professor of Medicine, Department of Medicine, Hematology and Medical Oncology, University of Arizona Cancer Center, 1515 N Campbell Ave, Tucson, AZ 85724, United States. areciomd@email.arizona.edu
Telephone: +1-520-6264703 Fax: +1-520-6268095
Received: February 26, 2019
Peer-review started: February 27, 2019
First decision: July 31, 2019
Revised: September 3, 2019
Accepted: September 12, 2019
Article in press: September 12, 2019
Published online: October 15, 2019
Processing time: 232 Days and 9 Hours
Abstract
BACKGROUND

Gastrointestinal cancer (GICA) is associated with a higher incidence of venous thromboembolism (VTE) compared to other solid tumors, moreover, recurrent VTE and major bleeding (MB) complications during anticoagulation treatment have an associated increase rate. GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants (DOAC), especially with active cancer therapies.

AIM

To evaluate patient risk factors, effectiveness (VTE) and safety (MB) of DOACs and low molecular weight heparin (LMWH) in patients with active GICA-VTE.

METHODS

A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed. Inclusion criteria included active GI cancer diagnosed at any stage or treatment +/- 6 mo of VTE diagnosis, whom were prescribed 6 mo or more of DOACs or LMWH. The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events. Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor.

RESULTS

A total of 144 patients were prescribed anticoagulation, in which 106 fulfilled inclusion criteria apixaban (27.3%), rivaroxaban (34.9%) and enoxaparin (37.7%), and 38 were excluded. Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event, with 62% males, 80% Caucasian, 70% stage IV, pancreatic cancer (40.5%), 30% Khorana Score (≥ 3 points), and 43.5% on active chemotherapy. Sixty-four percent of patients completed anticoagulation therapy (range 1 to 43 mo). Recurrent VTE at 6 mo was noted in 7.5% (n = 3), 6.8% (n = 2) and 2.7% (n = 1) of patients on enoxaparin, apixaban and rivaroxaban, respectively (all P = NS). MB at 6 mo were 5% (n = 2) for enoxaparin, 6.8% (n = 2) for apixaban and 21.6% (n = 8) for rivaroxaban (overall P = 0.048; vs LMWH P = 0.0423; all other P = NS). Significant predictors of a primary or secondary outcome for all anticoagulation therapies included: Active systemic treatment (OR = 5.1, 95%CI: 1.3-19.3), high Khorana Score [≥ 3 points] (OR = 5.5, 95%CI: 1.7-17.1), active smoker (OR = 6.7, 95%CI: 2.1-21.0), pancreatic cancer (OR = 6.8, 95%CI: 1.9-23.2), and stage IV disease (OR = 9.9, 95%CI: 1.2-79.1).

CONCLUSION

Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.

Keywords: Direct oral anticoagulants; Low molecular weight heparin; Gastrointestinal cancer; Venous thromboembolism; Cancer associated thrombosis; Clinical risk

Core tip: Our study shows similar efficacy of low molecular weight heparin as compared to apixaban and rivaroxaban. However, side effect profiles of these new direct oral anticoagulants (DOAC)’s may lead to a preferred use of apixaban, which had lower bleeding events in the highly sensitive gastrointestinal cancer (GICA) patient population. GICA-venous thromboembolism (VTE) is a high-risk patient subpopulation and warrants additional dedicated prospective clinical analysis of the efficacy and safety of DOACs. In addition, evaluation of clinical predictors that may influence the risk of VTE recurrence and major bleeding should include GICA as a high-risk group.