Effect of major gastrointestinal tract surgery on the absorption and efficacy of direct acting oral anticoagulants (DOACs)

Abstract

Direct-acting oral anticoagulants (DOACs) have been introduced as alternatives to warfarin for stroke prevention in non-valvular atrial fibrillation and for treatment of venous thromboembolism. Many patients undergoing major gastrointestinal resections or bypass receive anticoagulants for various indications, including the treatment of thrombotic complication of surgery and prevention of visceral vessels events recurrence. DOACs have a wide therapeutic range that allows fixed dosing determined based on studies conducted in healthy subjects with normal absorptive capacity. Patients with significantly altered gastrointestinal tracts were not included in the Phase II and III studies that assessed DOAC efficacy and safety. The aim of this article is to review clinical data on DOACs use in patients with major surgical resection or bypass. MEDLINE and EMBASE were searched to identify studies and case reports of DOAC use in this population. Prescribing information for the four approved DOACs was also reviewed. The only types of available literature identified were case series and isolated case reports. Patients who underwent major distal intestinal resection were successfully anticoagulated with rivaroxaban, dabigatran was not effective. There is uncertainty about the efficacy of rivaroxaban and dabigatran in patients requiring anticoagulation after Roux-en-Y gastric bypass. Avoidance of rivaroxaban therapy in patients undergoing gastrectomy is advised Data are lacking regarding anticoagulation using apixaban and edoxaban in patients with major gastrointestinal resection or bypass is lacking. Clinicians should be aware of these limitations when using DOACs in this group of patients.

Home Parenteral Nutrition: Vascular Access and Related Complications

“…Patients requiring HPN may require LMWH as the underlying etiology of IF (eg, short bowel syndrome or mechanical obstruction) may preclude enteral absorption of warfarin. The non–vitamin K oral anticoagulants (NOACs) may prove useful in patients with IF as they need little monitoring; however, there are concerns that poor absorption may lead to reduced efficacy 107 . Early case reports suggest that these drugs can be effective in short bowel syndrome, but further research is needed to confirm efficacy 108 …”

Cancer-Associated Venous Thromboembolism: A Practical Review Beyond Low-Molecular-Weight Heparins

“…Rivaroxaban must be taken with food ( 3 ) and requires administration within the stomach (PEG tube) to ensure consistent bioavailability ( 28 , 29 ). Apixaban can be given independent of food intake via PEG/PEJ tubes ( 30 ). There are limited data for edoxaban, and currently it is only recommended as an intact tablet ( 31 ).…”

How I treat cancer-associated thrombosis

“…Patients with cancer often undergo surgical procedures which result in anatomic changes and might affect GI absorption of DOAC, such as total/partial gastrectomy, Roux-en-Y gastric bypass (RYB) or colectomy 29. Because of the location of absorption of rivaroxaban, which is predominantly in the stomach, total gastrectomy might affect its bioavailability 30.…”

“…Its bioavailability is probably less affected by gastric resection and possibly reduced by colectomy. Levels of edoxaban, on the other hand, are possibly reduced in patients with a history of gastric resection and RYB and unlikely affected in patients who underwent colectomy 29 32. In the absence of dedicated studies assessing the efficacy of DOAC after GI resection or bypass in patients with cancer, most statements are based on extrapolations from data on physiology of DOAC absorption, case reports and case series of patients mainly in bariatric surgery 29 33…”