Safety and Efficacy of Rivaroxaban and Apixaban in Patients with Increased Body Mass: a Systematic Review

Abstract

Background and objective: Rivaroxaban and apixaban are direct oral anticoagulants increasing in popularity as convenient alternatives to warfarin. However, current guidelines recommend against use in patients with a BMI > 40 kg/m² or bodyweight > 120 kg unless drug-specific levels are measured, which may not be feasible across all clinical practices. Accordingly, the objective of this study was to broadly examine literature evaluating the clinical outcomes of rivaroxaban and/or apixaban in patients with increased body mass.

Methods: A systematic literature review (guided by PRISMA) was performed through January 27, 2021 using PubMed, Embase, and Scopus. Key search term clusters included drug and weight-related concepts (overweight/obese, body mass index [BMI], waist circumference). DistillerSR was utilized to review and process search results. Studies met inclusion if they analyzed the risk of bleeding and/or thrombosis in patients with increased body mass (i.e., via BMI or other criteria) receiving rivaroxaban or apixaban. Clinical guidelines, case reports/series, pharmacokinetic/dynamic analyses, and commentaries were excluded. Bias was examined qualitatively across studies.

Results: After duplicates were removed, the original search rendered 1822 abstracts and 200 full-texts for screening, ultimately providing a final set of 24 studies for qualitative review. Of these studies, 13 (54.2%) enabled comparisons between patients of increased versus normal body mass, while 11 (45.8%) reported outcomes only for patients of increased body mass. The working definition of 'increased body mass' varied amongst the studies, including 11 (45.8%) studies that utilized BMI, seven (29.2%) with a combination of BMI and body measurement, two (8.3%) that relied on body weight alone, and four (16.7%) that identified obesity-related ICD codes. All 13 comparative studies found similar or reduced rates of safety and efficacy outcomes with rivaroxaban and apixaban.

Conclusion: The literature reports similar or lower bleeding and thrombotic risk for rivaroxaban and apixaban in patients of increased body mass compared to patients of normal body mass. Future prospective controlled studies are needed to further define guidelines for use in this population.