Meta-Analysis Comparing Direct Oral Anticoagulants Versus Warfarin in Morbidly Obese Patients With Atrial Fibrillation

doi:10.1016/j.amjcard.2020.03.048

The American Journal of Cardiology

Volume 126, 1 July 2020, Pages 23-28

https://doi.org/10.1016/j.amjcard.2020.03.048 Get rights and content

Highlights

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Direct oral anticoagulants did not increase stroke or systemic embolism event rate.
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Direct oral anticoagulants had lower major bleeding rate than warfarin.
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Direct oral anticoagulants are considered as an option in morbidly obese patients.
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A randomized controlled trial is needed to confirm our meta-analysis results.

The International Society of Thrombosis and Haemostasis recommends warfarin therapy over direct oral anticoagulants (DOACs) in patients with a body mass index >40 kg/m² or weight > 120 kg due to limited clinical data in morbidly obese patients. The aim of the meta-analysis was to compare DOACs with warfarin in morbidly obese patients with atrial fibrillation (AF) and to optimize an anticoagulation therapy in the population. MEDLINE, Embase, Google Scholar, Web of Science, and Cochrane Library database searches for relevant articles through December 23, 2019 were performed. Total 5 studies for the event rate of stroke or systemic embolism (SE) and 4 studies for major bleeding were included in the meta-analysis. It showed that there was no statistically significant difference in stroke or SE event rate between the DOAC and warfarin groups (odds ratio: 0.85; 95% confidence interval: 0.60, 1.19; p = 0.35; I² = 0 %). The DOAC use was significantly associated with a lower major bleeding event rate compared the warfarin group (odds ratio: 0.63; 95% confidence interval: 0.43, 0.94; p = 0.02; I² = 30%). In conclusion, DOACs should be considered as an oral anticoagulant for preventing stroke or SE in morbidly obese patients with AF. A randomized controlled trial comparing a DOAC with warfarin is needed to confirm our meta-analysis results in morbidly obese patients with AF.

Section snippets

Methods

MEDLINE, Embase, Google Scholar, Web of Science, and Cochrane Library database searches for relevant articles through 12/23/19 were performed. The keywords used were (dabigatran OR rivaroxaban OR apixaban OR edoxaban OR warfarin) AND (obese OR obesity).

Two reviewers (KK, MH) independently performed the study selection based on the pre-specified inclusion and exclusion criteria. Studies were included if included patients are aged > 18 years old with BMI > 40 kg/m² or weight > 120 kg receiving

Results

A total of 321 studies was screened and 16 studies were assessed for eligibility. Of those studies reviewed, 5 studies were included for our meta-analysis (Figure 1).9, 10, 11, 12, 13

The study by Aloi et al¹⁴ was excluded because patients receiving warfarin were not included as a control group. The post hoc study of the ARISTOLE trial by Sandhu et al¹⁵ was excluded because another post hoc study by Hohnloser et al included the same cohort. The study by Kalani et al¹⁶ was also excluded because

Discussion

Our meta-analysis showed there was no significant difference in the event rate of stroke or SE between the DOAC and warfarin cohorts with AF, but the DOAC use was significantly associated with lower major bleeding event rate compared with the warfarin group.

The pivotal phase 3 clinical trials compared a DOAC with warfarin in general population with nonvalvular AF, and they showed that the DOAC therapy showed noninferiority or superiority to the warfarin therapy in the prevention of stroke or SE.

Authors’ Contribution

Kazuhiko Kido: conceptualization, investigation, methodology, writing-original draft and writing-review and editing; Mikiko Shimizu: methodology, software, writing-review and editing; Tsuyoshi Shiga: Conceptualization, resources, writing-review and editing; Masayuki Hashiguchi: supervision, software, investigation, writing-review and editing.

Disclosures

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Tsuyoshi Shiga is a member of the speaker bureau for Bristol-Myers Squibb.

Acknowledgement

Authors would like to thank Dr. Renato Lopes MD, Ph.D for providing us with additional information on the included study by Hohnloser et al for data analysis. Without your help, we could not have completed this meta-analysis.

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Cited by (27)

Safety and efficacy of direct oral anticoagulants in comparison with warfarin across different BMI ranges: A systematic review and meta-analysis
2022, Annals of Medicine and Surgery
Citation Excerpt :
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 [34-57]. Many limitations were acknowledged in our study, consequently further studies should take into account these restrictions when collecting data.
Many publications have compared various outcomes defining safety and efficacy of DOACs across different BMI ranges. Our meta-analysis compares warfarin and DOACs for its treatment effects over different BMI ranges.
A systematic search was conducted from inception to May 2021 on PubMed, Scopus and Embase databases. The data was extracted and pooled using a random effects model. Our study consisted of patients being treated for VTE and AF, across different BMI categories. For the comparison of DOAC, risk ratios (RR) with 95% confidence intervals (CIs) were used, whilst for the second comparison between warfarin and DOACs odds ratios (OR) were used.
In our first comparison, 12 studies (n = 254,908 patients) were included. For our second comparison, six studies (n = 109,609 patients) were included. Major bleeding events in the underweight group were higher than normal weight [RR: 1.89 (1.10, 3.23); P = 0.02; I² = 0%]. Overweight patients were related with reduced rates of VTE than in patients with normal BMI [RR: 0.86 (0.76, 0.97); P = 0.02; I² = 0%]. In comparison with patients receiving warfarin, DOACs had significantly reduced risk of major bleeding in normal weight, overweight and obese [OR: 0.64 (0.49, 0.83); P = 0.0007 I² = 90%].
The risk of VTE reduces with an increasing BMI, hence there could be a possible obesity paradox in patients with anticoagulation therapy. In comparison to warfarin, DOACs proved to be the safer option by having a reduced risk of bleeding across all BMI categories.
Oral Anticoagulant Use in Morbid Obesity and Post Bariatric Surgery: A Review
2021, American Journal of Medicine
Citation Excerpt :
Hence, the results may not be generalizable to other patient populations. Similarly, another meta-analysis included 5 studies that evaluated use of DOAC and warfarin in morbidly obese patients with atrial fibrillation.20 It showed that there were no differences in stroke or thromboembolism in both groups (OR 0.85; 95% confidence interval, 0.60-1.19; P = 0.35; I2 = 0%).
Bariatric surgery has emerged as a therapy for obesity and the associated comorbidities. Obesity has been shown to be a risk factor for atrial fibrillation as well as venous thromboembolism, both of which are conditions that warrant anticoagulation. There is significant underrepresentation of the morbidly obese population in prospective trials that evaluated direct oral anticoagulants and vitamin K antagonists in atrial fibrillation and venous thromboembolism. We aim to review all the available data that assessed these oral anticoagulants in the morbidly obese population (body mass index >40 kg/m² and weight >120 kg) and in the post-bariatric surgery population. Our findings suggest that direct oral anticoagulants may be safe and effective for anticoagulation in morbidly obese patients for both atrial fibrillation and venous thromboembolism. However, warfarin is the preferred agent in the post-bariatric surgery population, given the limited number of studies on direct oral anticoagulants in this population. Further adequately powered randomized control trials are needed to confirm the safety and efficacy of these oral anticoagulants in the morbidly obese and post-bariatric surgery population.
Peak plasma rivaroxaban levels in patients weighing 120 kg or greater
2021, Thrombosis Research
Network Meta-Analysis Comparing Apixaban Versus Rivaroxaban in Morbidly Obese Patients With Atrial Fibrillation
2020, American Journal of Cardiology
Factor Xa Inhibitors versus warfarin in patients with morbid obesity and atrial fibrillation
2024, European Journal of Clinical Pharmacology
Therapeutic Drug Monitoring of Direct Oral Anticoagulants in Patients with Extremely Low and High Body Weight—Pilot Study
2023, Journal of Clinical Medicine

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: Funding: Dr. Kido received the American College of Clinical Pharmacy Cardiology Practice Research Network Seed Grant, 009389-00001 for this meta-analysis research, Lenexa.

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Meta-Analysis Comparing Direct Oral Anticoagulants Versus Warfarin in Morbidly Obese Patients With Atrial Fibrillation

Highlights

Section snippets

Methods

Results

Discussion

Authors’ Contribution

Disclosures

Acknowledgement

J Thromb Haemost

Lancet Haematol

Am Heart J

Dabigatran versus warfarin in patients with atrial fibrillation

N Engl J Med

Rivaroxaban versus warfarin in nonvalvular atrial fibrillation

N Engl J Med

Apixaban versus warfarin in patients with atrial fibrillation

N Engl J Med

Edoxaban versus warfarin in patients with atrial fibrillation

N Engl J Med

RoB 2: a revised tool for assessing risk of bias in randomised trials

BMJ