Efficacy and Safety of Direct-Acting Oral Anticoagulants (DOACs) in the Overweight and Obese

Abstract

Obesity plays an essential role in the safety of pharmacologic drugs. There is paucity of data for direct oral anticoagulants (DOACs) in the obese, despite these agents becoming more widely used. The primary and secondary objectives of this study were to assess the safety and efficacy of DOACs in the overweight and obese populations when used for primary prophylaxis in the setting of non-valvular atrial fibrillation (NVAF) and for treatment of venous thromboembolisms (VTE). We conducted a retrospective cohort study in a large tertiary care center and obtained data through review of electronic health records. Among patients with NVAF and VTE on apixaban, there were no differences in rates of major bleeding (MB) and clinically relevant nonmajor bleeding (CRNMB) in the overweight and obese populations when compared to normal weight and underweight individuals. The multivariate adjusted analysis for rivaroxaban found that the odds of CRNMB for patients with BMI <25 was 5.37 (95% CI 1.50–19.32) times higher than that of BMI ≥25. Moreover, patients on medications that had known interactions with DOACs had 6.40 times higher odds of CRNMB than patients without such interactions (95% CI 1.49–27.57), which was not accounted for by the effects of aspirin and plavix alone. Efficacy was similar between all weight groups, for both apixaban and rivaroxaban. These results support previous analyses preformed in the large phase III trials and confirm that apixaban and rivaroxaban are safe in the overweight and obese.

Apixaban and rivaroxaban in obese patients treated for venous thromboembolism: Drug levels and clinical outcomes

“…The other available data on obese patients are based on post hoc analyses of randomized trials, registries, retrospective studies or healthcare claims databases. These studies showed minor effects of obesity on DOAC PK and reported similar efficacy and safety of DOACs across the different weight groups, and versus vitamin K antagonists, suggesting DOAC efficacy and safety in obese patients [16][17][18][19][20][21][22][23][24][25][26].…”

Impact of Weight on Clinical Outcomes of Edoxaban Therapy in Atrial Fibrillation Patients Included in the ETNA-AF-Europe Registry

“…Moreover, some of these studies had incomplete adjustment for confounding factors at baseline and the others were limited by small sample size and retrospective nature of the analyses. Higher BMI and waist circumference were associated with a favourable prognosis (adjusting for comorbidities and treatment allocation) in patients treated with oral anticoagulants [31,32]. In an analysis of patients treated with edoxaban and warfarin included in the ENGAGE AF-TIMI 48 trial, higher BMI (per 5 kg/m 2 increase) was independently associated with lower risks of stroke/SEE and death, but with increased risk of major bleeding.…”

Safety and efficacy of direct oral anticoagulants in comparison with warfarin across different BMI ranges: A systematic review and meta-analysis

“…More investigation should be done debating whether warfarin or NVKAs are the better choice for high risk VTE patients. According to the linked studies, DOACs remain to be the preferable choice regardless, due to their rapid onset of action, standard dosages without the need of titration, lack of requirement of routine check-ups, and limited interactions with food and associated drugs [ [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] ].…”