To provide guidance about the management of direct oral anticoagulants (DOACs) in obese patients.Four DOACs are approved for clinical use in Canada: apixaban, dabigatran, edoxaban and rivaroxaban. The clinical guides for each of the DOACs contains information about mechanism of action, licensed indications, side-effect profiles, and approved dosing regimens . According to the Health Canada, obesity is defined by a body mass index (BMI) >30 kg/m 2 .No randomized controlled trials have examined the safety and efficacy of DOACs only in obese or very obese patients. In most instances, 90-100 kg or BMI >30 kg/m 2 . A high weight alone does not necessarily indicate obesity, thereby limiting the interpretation of data from trials that reported weight only. Although information remains somewhat limited for some indications, based on the data below, there is increasing comfort using DOACs in patients with class I (BMI 30.0-34.9) and class II (BMI 35.0-39.9) obesity.# 
- Studies in venous thromboembolism: In a systematic review and meta-analysis of patients with VTE treated with apixaban, dabigatran, and rivaroxaban, anticoagulant efficacy was similar in patients 100kg or <100kg groups.
- Studies in atrial fibrillation: A systematic review and subsequently published post-hoc subgroup analyses of large randomized trials suggest that, among atrial fibrillation patients, apixaban, dabigatran, rivaroxaban and edoxaban are equivalent to vitamin K antagonists in terms of efficacy and safety in obese patients. A retrospective study was done at an integrated multisite health-care system of DOAC use across all BMI categories. No differences were found in stroke rates or risk of intracranial hemorrhage between normal BMI and those with category 1 or higher obesity (43.9% apixaban, 36.4% rivaroxaban, 9.5% dabigatran and 0.1% edoxaban).
- Studies in orthopedic surgery: In a study that compared clinical outcomes in patients undergoing total hip and knee arthroplasty, no significant differences between the efficacy and safety of dabigatran and enoxaparin in patients with a BMI>30 were noted. A study evaluating patients undergoing total hip or knee arthroplasty found no differences in the reduction in venous thromboembolism (VTE) risk with rivaroxaban versus enoxaparin in patients >90kg compared with those with lower weights. Finally, in a subgroup analysis of pooled data from studies comparing apixaban and enoxaparin, there were no differences in VTE or bleeding events when patients with BMI30. ) or warfarin (1208 patients) and who had a body weight more than 100 kg and less than 300 kg, no significant difference was seen in the rate of recurrent venous thromboembolism or bleeding in the two treatment groups. In this study, the median BMI was 38.8 kg/m2 in the DOAC group and 39.2 kg/m2 in the warfarin group; in the DOAC group, 43.6% had a BMI >40, while in the warfarin group this was 45.3%. - A retrospective 1:1 propensity score matched cohort study of 2890 VTE patients from US claims data (using ICD-9 and ICD-10 codes for morbid obesity) showed similar bleeding and recurrent VTE risk between warfarin and rivaroxaban. A similar study from the same group looking at 3563 atrial fibrillation patients showed similar bleeding and stroke/systemic embolism risk between warfarin and rivaroxaban.
- If DOACs are to be used in patients with a BMI >40 or >120 kg, patients should be informed of the limitations of the available information and potential risk of under-dosing.

# SPECIAL CONSIDERATIONS:
Data regarding safety and efficacy of DOACs in the pediatric population are very limited. DOACs are contraindicated in pregnancy and while breast feeding.

# OTHER RELEVANT THROMBOSIS CANADA CLINICAL GUIDES:
- Apixaban (Eliquis)
- Dabigatran (Pradaxa) 

# Date of version: 29August2021
Please note that the information contained herein is not to be interpreted as an alternative to medical advice from your doctor or other professional healthcare provider. If you have any specific questions about any medical matter, you should consult your doctor or other professional healthcare providers, and as such you should never delay seeking medical advice, disregard medical advice or discontinue medical treatment because of the information contained herein.