Direct Oral Anticoagulants Versus Warfarin in Morbidly Obese Patients With Nonvalvular Atrial Fibrillation

Background: Direct oral anticoagulants (DOACS) were recently approved for anticoagulation in patients with atrial fibrillation for prevention of stroke and patient with venous thromboembolism (VTE) for the prevention of recurrent VTE. They have shown comparable efficacy and safety compared to vitamin K antagonist (VKA). DOACS have uniform pharmacokinetics and pharmacodynamics; hence, regular monitoring is not required. The morbidly obese patients may have increased volume of distribution and altered clearance which may alter the pharmacokinetics and consequently efficacy and safety of DOACS in these patients. 2016 International Society of Thrombosis and Hemostasis guideline recommends avoiding DOACS in a patient with body mass index (BMI) >40 kg/m2 or with body weight >120 kg due to lack of clinical trials. There is no sizeable randomized control trial to study the outcome of DOACS in morbidly obese patients, but subgroup analysis of a major randomized control trials and observational studies may provide the data on the efficacy and safety of DOACS. We intend to utilize this data in this meta-analysis to study the effectiveness and safety of DOACS in morbidly obese patients. Methods: Eligibility Criteria- Randomized control trial, observational studies including patients above 18 years with BMI>40kg/m2, body weight>120 kg and history of atrial fibrillation or VTE who are taking DOACS or warfarin for therapeutic purpose were included in the analysis. Study Selection- We searched Medline and Cochrane database. 52 studies were identified and 43 remained after removing duplicates. After assessing full text for eligibility 5 studies were included in the meta-analysis. Statistical analysis- Statistical analysis was performed with Review manager 5.3 by the Cochrane Collaboration. Forest plot was used to analyze publication bias. Heterogeneity in the studies were analyzed with Cochran Q analysis and I2 statistics. Results: Population characteristics were available in four studies. The mean age of the population ranged from 61.7 to 66.8 years, and mean BMI ranged from 44.8 to 46.7 kg/m2 . I2 analysis showed that the studies included were homogeneous, so fixed-effect model was applied. The incidence of recurrent VTE, stroke, or death ranged from 1.5% to 7.3% in DOACS compared to 1.2% to 7.9% in warfarin except in one study by Kalani et al. where it was 26% in DOACS vs. 20% in warfarin. Relative risk was 0.96 (confidence interval 0.75 - 1.28, p 0.78) indicating there was no significant difference in the primary efficacy outcome between the two groups. The incidence of major bleeding ranged from 1.5% to 4.8% in DOACS compared to 2.6% to 6.1% in warfarin. Relative risk was 0.72 (confidence interval 0.56 - 0.93, p 0.01) indicating that the risk of major bleeding was low among patient using DOACS. Conclusion: Efficacy of DOACS is similar compared to VKA when used for prevention of recurrence in VTE or prevention of stroke in atrial fibrillation in the patients with BMI>40 kg/m2 or bodyweight >120 kg. There was a trend towards a lower risk of bleeding in the patients with DOACS which is similar to the risk of major bleeding reported in non-obese patients in landmark randomized clinical trials. Only two studies included the patients with VTE, and additional studies are required to assess the safety and efficacy of DOACS among morbidly obese individuals with VTE. Figure Disclosures No relevant conflicts of interest to declare.

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Efficacy and safety of direct oral anticoagulants in morbidly obese patients with non-valvular atrial fibrillation: a systematic review and meta-analysis

European Heart Journal ◽

10.1093/eurheartj/ehab724.3424 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

M Mhanna ◽

A Beran ◽

A Al-Abdouh ◽

O Srour ◽

W Abdulsattar ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Morbidly Obese ◽

Obese Patients ◽

Efficacy And Safety ◽

Systemic Embolism ◽

Warfarin Group

Abstract Introduction Atrial fibrillation (AF) is the most common arrhythmia, with an estimated prevalence between 1–4%. On the other hand, obesity continued to be a prevalent health issue worldwide. Direct oral anticoagulants (DOACs) have been increasingly preferred over warfarin; however, The International Society of Thrombosis and Hemostasis (ISTH) recommended avoiding the use of DOACs in patients with a BMI >40 or weight >120 kg because of limited clinical data in these patients. In this meta-analysis, we aimed to evaluate the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. Method We performed a comprehensive literature search using multiple databases from database inception through January 2021, for all the studies that evaluated the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. The primary outcome of interest was stroke or systemic embolism (SSE) rate. The secondary outcome was major bleeding (MB). All meta-analyses were conducted using a random-effect model. Results A total of 10 studies including 89,494 morbidly obese patients (BMI >40 or weight >120 kg) with non-valvular AF on oral anticoagulation therapy (45427 on DOACs vs. 44067 on warfarin) were included in the final analysis. One included study was a randomized controlled trial (RCT), another study was a post hoc analysis of an RCT and the rest were retrospective cohort studies. The mean follow-up period was 1.8 years (range 8 months to 3.1 years). The SSE rate was significantly lower in DOACs group compared to warfarin group (odds ratio (OR): 0.71; 95% confidence interval (CI): 0.62, 0.81; p<0.0001; I2=0%). MB rate was also significantly lower in DOACs group compared to the warfarin group (OR 0.60, 95% CI 0.46–0.78, P<0.0001, I2=86%). Subgroup analysis in the rivaroxaban and apixaban AF cohort showed a statistically significant difference in SSE and MB event rates favoring both over warfarin therapy. Dabigatran showed non-inferiority to warfarin in SSE rate but superiority in the safety outcome. Conclusions Our meta-analysis demonstrated that DOACs are effective and safe when compared to warfarin in morbidly obese patients. However, more large scale randomized clinical trials are needed to further evaluate the efficacy and safety of DOACs compared to warfarin in this cohort of patients. FUNDunding Acknowledgement Type of funding sources: None. Stroke and systemic embolism events Major bleeding events

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Direct oral anticoagulants are effective and safe in the treatment of venous thromboembolism and atrial fibrillation in morbidly obese patients

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-020-02238-w ◽

2020 ◽

Author(s):

Mouhand F. H. Mohamed ◽

Hazem Elewa ◽

Mahmood Mubasher ◽

Mohammed Danjuma

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Morbidly Obese ◽

Obese Patients

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Comparing the Efficacy and Safety of Direct Oral Anticoagulants With Warfarin in the Morbidly Obese Population With Atrial Fibrillation

Annals of Pharmacotherapy ◽

10.1177/1060028018796604 ◽

2018 ◽

Vol 53 (2) ◽

pp. 165-170 ◽

Cited By ~ 23

Author(s):

Kazuhiko Kido ◽

Surachat Ngorsuraches

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Rate Ratio ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Morbidly Obese ◽

Obese Patients ◽

Efficacy And Safety ◽

Warfarin Group ◽

Group Rate

Background: The International Society of Thrombosis and Haemostasis recommends avoiding direct oral anticoagulants (DOACs) in morbidly obese patients with a body mass index (BMI) >40 kg/m2 or weight >120 kg because of limited clinical data in this group of patients. Objectives: The objective of this study was to evaluate the efficacy and safety of DOACs in morbidly obese patients with atrial fibrillation or flutter. Methods: A retrospective, single-center cohort study was conducted of patients older than 18 years, with BMI >40 kg/m2 or weight >120 kg, who were diagnosed as having atrial fibrillation or flutter and who received warfarin or DOACs (ie, dabigatran, rivaroxaban, or apixaban). The primary efficacy outcome was the incidence of ischemic stroke or transient ischemic attack (TIA), whereas the primary safety outcome was the incidence of major bleeding. Results: A total of 64 patients in each group were included in the study analysis. The incidence rate of ischemic stroke or TIA was 1.75%/year in the DOAC group compared with 2.07%/year in the warfarin group (rate ratio = 0.84; 95% CI = 0.23 to 3.14; P = 0.80). The incidence rate of major bleeding was 2.18%/year in the DOAC group, compared with 4.97%/year in the warfarin group (rate ratio = 0.44; 95% CI = 0.15 to 1.25; P = 0.11). Conclusion and Relevance: Apixaban and rivaroxaban may be considered as alternatives to warfarin for atrial fibrillation or flutter in morbidly obese patients. Dabigatran use in morbidly obese patients needs caution until further studies are conducted.

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