title: Is There an Obesity Paradox for Outcomes in Atrial Fibrillation? A Systematic Review and Meta-Analysis of Non-Vitamin K Antagonist Oral Anticoagulant Trials.
abstract: OBJECTIVE
  Obesity is a risk factor for all-cause and cardiovascular death but, despite this, an inverse relationship between overweight or obesity and a better cardiovascular prognosis in long-term follow-up studies has been observed; this phenomenon, described as obesity paradox, has also been found evident in atrial fibrillation cohorts.
  
  
  METHODS
  We performed a systematic review on the relationship between body mass index and major adverse outcomes in atrial fibrillation patients. Moreover, we provided a meta-analysis of non-vitamin K antagonist oral anticoagulants (NOACs) trials.
  
  
  RESULTS
  An obesity paradox was found for cardiovascular death and all-cause death in the subgroup analyses of randomized trial cohorts; however, observational studies fail to show this relationship. From the meta-analysis of NOAC trials, a significant obesity paradox was found, with both overweight and obese patients reporting a lower risk for stroke/systemic embolic event (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.66-0.84 and OR, 0.62; 95% CI, 0.54-0.70, respectively). For major bleeding, only obese patients were at lower risk compared with normal weight patients (OR, 0.84; 95% CI, 0.72-0.98). A significant treatment effect of NOACs was found in normal weight patients, both for stroke/systemic embolic event (OR, 0.66; 95% CI, 0.56-0.78) and for major bleeding (OR, 0.72; 95% CI, 0.54-0.95). Major bleeding risk was lower in overweight patients treated with NOACs (OR, 0.84; 95% CI, 0.71-1.00).
  
  
  CONCLUSIONS
  There may be an obesity paradox in atrial fibrillation patients, particularly for all-cause and cardiovascular death outcomes. An obesity paradox was also evident for stroke/systemic embolic event outcome in NOAC trials, with a treatment effect favoring NOACs over warfarin for both efficacy and safety that was significant only for normal weight patients.
authors.affiliation: From the University of Birmingham Institute of Cardiovascular Sciences, Birmingham, United Kingdom (M.P., E.G., P.C., G.Y.H.L.); Department of Internal Medicine and Medical Specialties (M.P., E.G.) and Department of Life, Health and Environmental Sciences (P.C.), University of L'Aquila, Italy; and Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L.).
authors.forename: Marco
authors.initials: M
authors.lastname: Proietti
authors.affiliation: From the University of Birmingham Institute of Cardiovascular Sciences, Birmingham, United Kingdom (M.P., E.G., P.C., G.Y.H.L.); Department of Internal Medicine and Medical Specialties (M.P., E.G.) and Department of Life, Health and Environmental Sciences (P.C.), University of L'Aquila, Italy; and Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L.).
authors.forename: Elisa
authors.initials: E
authors.lastname: Guiducci
authors.affiliation: From the University of Birmingham Institute of Cardiovascular Sciences, Birmingham, United Kingdom (M.P., E.G., P.C., G.Y.H.L.); Department of Internal Medicine and Medical Specialties (M.P., E.G.) and Department of Life, Health and Environmental Sciences (P.C.), University of L'Aquila, Italy; and Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L.).
authors.forename: Paola
authors.initials: P
authors.lastname: Cheli
authors.affiliation: From the University of Birmingham Institute of Cardiovascular Sciences, Birmingham, United Kingdom (M.P., E.G., P.C., G.Y.H.L.); Department of Internal Medicine and Medical Specialties (M.P., E.G.) and Department of Life, Health and Environmental Sciences (P.C.), University of L'Aquila, Italy; and Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L.). g.y.h.lip@bham.ac.uk.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000453:epidemiology* / Q000401:mortality; D004617:Embolism / Q000188:drug therapy / Q000453:epidemiology* / Q000401:mortality; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D009765:Obesity / Q000453:epidemiology* / Q000401:mortality; D050177:Overweight / Q000453:epidemiology* / Q000401:mortality
chemical_list: D000925:Anticoagulants
keywords: anticoagulants; atrial fibrillation; body weight; heart failure; obesity