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Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation and (Morbid) Obesity or Low Body Weight: a Systematic Review and Meta-Analysis

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Abstract

Purpose

Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in the general AF population. However, as NOACs are administered in fixed doses, concerns of unintentional underdosing in morbidly obese patients and unintentional overdosing in underweight patients have emerged. Therefore, a critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum is needed.

Methods and Results

After searching Medline, this systematic review discusses the impact of body weight on the risk-benefit profile of NOACs versus VKAs. The meta-analysis demonstrated that NOAC use in obese and class III obese AF patients (body mass index (BMI) ≥ 30 and ≥ 40 kg/m2, respectively) was associated with significantly lower stroke/systemic embolism (stroke/SE) risks (RR 0.82, 95%CI [0.71–0.96] and RR 0.75, 95%CI [0.64–0.87], respectively), similar to lower major bleeding risks (RR 0.83, 95%CI [0.69–1.00] and RR 0.74, 95%CI [0.57–0.95], respectively) and similar mortality risks (RR 0.92, 95%CI [0.73–1.15] and RR 1.17, 95%CI [0.83–1.64], respectively) compared to VKAs. In AF patients ≤ 60 kg, significantly lower stroke/SE (RR 0.63, 95%CI [0.56–0.71]) and major bleeding risks (RR 0.71, 95%CI [0.62–0.80]), but similar mortality risks (RR 0.68, 95%CI [0.42–1.10]), were observed for NOAC- versus VKA-treated patients.

Conclusion

The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight. However, more data are needed on underweight AF patients (BMI < 18.5 kg/m2) and on differences between NOACs in these patients.

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Data Availability

The data underlying this article are available in the article and in its online supplemental materials.

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Funding

This research was supported by grants from the Fund for Scientific Research Flanders (FWO) [grant number 11C0820N to Maxim Grymonprez].

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Authors and Affiliations

  1. Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium

    Maxim Grymonprez, Koen Boussery & Lies Lahousse

  2. Department of Cardiology, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium

    Tine L. De Backer

  3. Centre for Pharmaceutical Research, Research group of Clinical Pharmacology and Clinical Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Jette, Belgium

    Stephane Steurbaut

  4. Department of Epidemiology, Erasmus Medical Center, Doctor Molewaterplein 40, 3015, Rotterdam, The Netherlands

    Lies Lahousse

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Contributions

Maxim Grymonprez and Lies Lahousse contributed to the concept and design of the systematic review. Maxim Grymonprez performed the literature search, data analysis, interpretation and writing. The first draft of the manuscript was written by Maxim Grymonprez. Tine De Backer, Stephane Steurbaut, Koen Boussery and Lies Lahousse revised the manuscript critically. All authors read and approved the final manuscript.

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Correspondence to Maxim Grymonprez.

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Grymonprez, M., De Backer, T.L., Steurbaut, S. et al. Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation and (Morbid) Obesity or Low Body Weight: a Systematic Review and Meta-Analysis. Cardiovasc Drugs Ther 36, 749–761 (2022). https://doi.org/10.1007/s10557-020-07122-6

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