The impact of underweight and obesity on outcomes in anticoagulated patients with atrial fibrillation: A systematic review and meta-analysis on the obesity paradox

Abstract

Although obesity is associated with the development and progression of atrial fibrillation (AF), an obesity paradox may be present, illustrated by seemingly protective effects of obesity on AF-related outcomes. Body mass index (BMI) has an impact on outcomes in AF patients using oral anticoagulants. After searching Medline and Embase, meta-analysis of results of four randomized and five observational studies demonstrated significantly lower risks of stroke or systemic embolism (RR 0.80, 95%CI [0.73-0.87]; RR 0.63, 95%CI [0.57-0.70]; and RR 0.42, 95%CI [0.31-0.57], respectively) and all-cause mortality (RR 0.73, 95%CI [0.64-0.83]; RR 0.61, 95%CI [0.52-0.71]; and RR 0.56, 95%CI [0.47-0.66], respectively) in overweight, obese and morbidly obese anticoagulated AF patients (BMI 25 to <30, ≥30 and ≥40 kg/m² , respectively) compared to normal BMI anticoagulated AF patients (BMI 18.5 to <25 kg/m² ). In contrast, thromboembolic (RR 1.92, 95%CI [1.28-2.90]) and mortality (RR 3.57, 95%CI [2.50-5.11]) risks were significantly increased in underweight anticoagulated AF patients (BMI <18.5 kg/m² ). In overweight and obese anticoagulated AF patients, the risks of major bleeding (RR 0.86, 95%CI [0.76-0.99]; and RR 0.88, 95%CI [0.79-0.98], respectively) and intracranial bleeding (RR 0.75, 95%CI [0.58-0.97]; and RR 0.57, 95%CI [0.40-0.80], respectively) were also significantly lower compared to normal BMI patients, while similar risks were observed in underweight and morbidly obese patients. This meta-analysis demonstrated lower thromboembolic and mortality risks with increasing BMI. However, as this paradox was driven by results from randomized studies, while observational studies rendered more conflicting results, these seemingly protective effects should still be interpreted with caution.

Keywords: anticoagulants; atrial fibrillation; body mass index; meta-analysis; obesity; underweight.

FIGURE 1

PRISMA flow diagram. AF: atrial fibrillation; BMI: body mass index; NOAC: non‐vitamin K antagonist oral anticoagulant; OAC: oral anticoagulant; PRISMA, preferred reporting items for systematic reviews and meta‐analyses; SE: systemic embolism; VKA: vitamin K antagonist; VTE: venous thromboembolism; WHO: World Health Organization

FIGURE 2

Forest plot of the risk of (A) stroke or systemic embolism, (B) all‐cause mortality, (C) major bleeding, and (D) intracranial bleeding for underweight (BMI <18.5 kg/m²) versus normal BMI (18.5 to <25 kg/m²) AF patients receiving anticoagulation, categorized according to randomized and observational studies. AF: atrial fibrillation; BMI: body mass index; CI: confidence interval; ENGAGE AF‐TIMI 48: the effective anticoagulation with factor Xa next generation in atrial fibrillation–thrombolysis in myocardial infarction 48 trial; M–H: Mantel–Haenszel (statistical method); RCT: randomized controlled trial

FIGURE 3

Forest plot of the risk of (A) stroke or systemic embolism, (B) all‐cause mortality, (C) major bleeding, and (D) intracranial bleeding for obese (BMI ≥30 kg/m²) versus normal BMI (18.5 to < 25 kg/m²) AF patients receiving anticoagulation, categorized according to randomized and observational studies. AF: atrial fibrillation; ARISTOTLE: the apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation trial; BMI: body mass index; CI: confidence interval; ENGAGE AF‐TIMI 48: the effective anticoagulation with factor Xa next generation in atrial fibrillation–thrombolysis in myocardial infarction 48 trial; M–H: Mantel–Haenszel (statistical method); RCT: randomized controlled trial; RE‐LY: the randomized evaluation of long‐term anticoagulation therapy; ROCKET AF: the rivaroxaban once daily oral direct factor Xa inhibition compared with vitamin k antagonism for prevention of stroke and embolism trial in atrial fibrillation

FIGURE 4

Overview of the meta‐analyzed risk estimates of stroke or systemic embolism, mortality, major bleeding and intracranial bleeding for underweight (BMI <18.5 kg/m²), overweight (25 to < 30 kg/m²), obese (≥30 kg/m²), Class II obese (35 to <40 kg/m²) and morbidly obese (≥40 kg/m²) versus normal BMI (18.5 to < 25 kg/m²) AF patients receiving anticoagulation, respectively. AF: atrial fibrillation; BMI: body mass index; CI: confidence interval; NR: not reported; RR: risk ratio; SE: systemic embolism