Role of direct oral anticoagulants in gastrointestinal cancer associated thrombosis “practical issues in clinical practice”—narrative review

Abstract

Direct oral anticoagulants (DOAC) are now considered an effective treatment option for cancer associated thrombosis (CAT). There are still controversies in the use of DOACs in CAT associated with gastrointestinal (GI) malignancies. Background: Patients with GI malignancies and CAT present several unique management challenges.Factors such as the risk of bleeding from intact luminal primary, impact on absorption and efficacy of the DOACs due to altered anatomy, chemotherapy-induced nausea and vomiting, the potential drug to drug interactions need to be considered when prescribing DOACs in CAT associated with GI malignancies. Methods:The landmark randomised controlled trials (RCTs), systematic reviews and observational studies (OSs) of real-world data comparing DOACs with low molecular weight heparin (LMWH) in treating CAT comprised heterogeneous groups of tumour sites with limited numbers of patients with GI malignancies. This article reviews the available evidence on outcomes of the subset of CAT associated with GI malignancies in recent RCTs.Conclusions: Future prospective trials need to evaluate the impact of the factors mentioned above in the efficacy of DOACs in preventing and treating CATs in specific subsets of GI malignancies. Until more evidence is available, LMWH is a more reasonable choice in selected subgroups of CAT in GI malignancies.

Safety and Effectiveness of Direct Oral Anticoagulants for the Treatment of Gastrointestinal Cancer-Associated Venous Thromboembolism

“…The SELECT-D trial ( 10 , 27 ) showed rivaroxaban was associated with a relatively low VTE recurrence (4% with rivaroxaban and 11% with dalteparin; HR = 0.43) but higher incidence of CRNMB compared with dalteparin (6-month cumulative rate, 13% versus 4%, HR = 3.76), and similar MB (6% vs 4%, HR = 1.83). An interim safety analysis revealed that 36% of MB in the rivaroxaban group had esophageal or gastroesophageal cancer, compared to 5% with dalteparin leading to subsequent exclusion of these cancer types from enrolment as a precautionary measure ( 17 ).…”

“…An interim safety analysis revealed that 36% of MB in the rivaroxaban group had esophageal or gastroesophageal cancer, compared to 5% with dalteparin leading to subsequent exclusion of these cancer types from enrolment as a precautionary measure ( 17 ). The ADAM-VTE trial ( 11 , 27 ) hypothesized that apixaban was associated with a significantly lower MB rate compared to dalteparin, failed to show the superiority of apixaban in term of MB (0% of 145 patients receiving apixaban vs 1.4% of 142 patients receiving dalteparin; P = . 138) or CRNMB (6.2% in apixaban vs 6.3% in dalteparin, P = .…”

“…VTE recurrence was lower for apixaban (0.7%) than for dalteparin (6.3%, HR=0.099). The Caravaggio trial ( 13 , 19 , 27 ) showed that apixaban was noninferior to dalteparin for recurrent CA-VTE (HR = 0.63, P < . 001 for noninferiority; P = .…”

Challenges to Laboratory Monitoring of Direct Oral Anticoagulants

“… 38 For patients with GI malignancies undergoing resection, DOACs may present additional management challenges, such as the risk of bleeding from luminal primary tumors, and the impact on DOAC absorption and efficacy due to altered anatomy or chemotherapy-induced nausea and vomiting. 39 …”