Introduction

European Society of Gastrointestinal Endoscopy (ESGE) guideline recommends an interruption of direct oral anticoagulant (DOAC) for >48 hours before high-risk endoscopic procedures based on weak evidence, particularly in the Asian population. (1) Previous studies demonstrated DOAC levels <50ng/mL were safe before invasive procedures. (2-4) We aim to determine the optimal DOAC interruption by pharmacokinetic measurements.

Aims & Methods

We conducted an industry-independent, prospective cohort study in Hong Kong from December 2021 to March 2023. Consecutive subjects on DOAC who required elective high-risk colonoscopic procedures (polypectomy, endoscopic mucosal resection, endoscopic submucosal dissection) were recruited. Subjects with end-stage renal failure (estimated glomerular filtration rate (eGFR) <15 ml/min) were excluded. All subjects withheld DOAC for at least 48 hours before procedures. Serum DOAC levels were collected at three time points after last dose – peak (2 hours), day before procedure (24 hours) and on day of procedure (48 hours). Samples were analysed by ACL TOP Hemostasis Testing Systems (Instrumentation Laboratory, Werfen Company). DOAC levels were generated by dilute thrombin time or calibrated anti-Xa assays and reported as ng/mL. DOAC levels were adjusted for sample collection time by piecewise linear function. Primary endpoint was proportion of subjects achieving minimal anticoagulant effect (defined as adjusted DOAC level <50ng/mL) at different pre-procedural time points. A stepwise logistic regression model was built to determine the clinical parameters associated with minimal anticoagulant effect.

Results

100 subjects were recruited with 13 subjects excluded due to incorrect DOAC interruption or missed sample collection. Among the 87 subjects included, there were 57 apixaban (65.5%), 18 dabigatran (20.7%), 8 edoxaban (9.2%) and 4 rivaroxaban (4.6%) users. (Table 1) Mean adjusted DOAC levels were 197.4 ng/mL at peak, 59.2 ng/mL at 24 hours, and 12.0 ng/mL at 48 hours post-dose. 58.6% (51/87) and 98.9% (86/87) of subjects achieved minimal anticoagulant effect with DOAC levels <50ng/mL at 24 and 48 hours post-dose respectively. Two subject (2.3%) developed delayed post-polypectomy bleeding. In multivariate analysis, eGFR was the only independent factor associated with minimal residual DOAC effect at 24 hours post-dose. Subjects with normal renal function (eGFR ≥60) were associated with significantly higher chance to achieve DOAC levels <50ng/mL at 24 hours than those with renal impairment (eGFR <60) (70.0% vs 41.7%, relative risk 1.68, 95%CI 1.10-2.57, p = 0.014). (Figure 1)

Table 1. Baseline characteristics of direct oral anticoagulants (DOAC) users and adjusted DOAC levels at different time points

Conclusion

Current ESGE guideline on DOAC interruption for >48 hours before high-risk endoscopic procedures was validated prospectively in Asian population. In selected subjects with normal renal function, a shorter DOAC interruption for 24 hours could be considered to minimise the peri-operative thromboembolism.

References

1. Veitch AM, Radaelli F, Alikhan R, et al. Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update. Gut. 2021 Sep;70(9):1611-1628.
2. Douketis JD, Spyropoulos AC, Duncan J, et al. Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant. JAMA Intern Med. 2019 Nov 1;179(11):1469-1478.
3. Godier A, Dincq AS, Martin AC, et al. Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study. Eur Heart J. 2017 Aug 14;38(31):2431-2439.
4. Shaw JR, Li N, Vanassche T, et al. Predictors of preprocedural direct oral anticoagulant levels in patients having an elective surgery or procedure. Blood Adv. 2020 Aug 11;4(15):3520-3527.

Disclosure

This study was partially supported by General Research Fund, University Grants Committee, Hong Kong. It was registered in ClinicalTrial.gov as NCT05378035.
LHSL has received research grant from GenieBiome Ltd. and served as lecture speaker for Olympus Co. Ltd., Boston Scientific Co. Ltd. and GenieBiome Ltd. VWSW is a co-founder of Illuminatio Medical Technology Limited, and has received research grant from Gilead Sciences, and served as a consultant for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, and served as a lecture speaker for Abbott, AbbVie, Gilead Sciences, Novo Nordisk, Unilab. FKLC is the scientific co-founder of GenieBiome Ltd. and has served as an advisor and lecture speaker for Eisai Co. Ltd., AstraZeneca, Pfizer Inc., Takeda Pharmaceutical Co., and Takeda (China) Holdings Co. Ltd. All other co-authors do not have any conflicts of interest to disclose.