Abstract
Obesity, a chronic disease established as a global epidemic by the World Health Organization, is considered a risk factor for atrial fibrillation (AF), the most common sustained cardiac arrhythmia, which has high morbidity and mortality. Although both obesity and AF are diseases associated with negative outcomes, studies have shown the presence of an obesity paradox, in which patients with a high body mass index (BMI) and AF have a better prognosis than patients with a normal BMI. Despite the fact that the mechanisms that lead to this paradox are still uncertain, adequate anticoagulation in obese patients seems to play an important role in reducing adverse events in this group. In this perspective article, the authors discuss the relationship between new oral anticoagulants (NOACs), namely, apixaban, edoxaban and rivaroxaban (factor Xa inhibitors) and dabigatran (direct inhibitor of thrombin), and the obesity paradox, seeking to deepen the understanding of the mechanism that leads to this paradox.
Keywords: Obesity, new oral anticoagulants, atrial fibrillation, obesity paradox, apixaban, edoxaban, rivaroxaban, dabigatran.
Graphical Abstract
[1]
Abrantes MM, Lamounier JA, Colosimo EA. Overweight and obesity prevalence among children and adolescents from Northeast and Southeast regions of Brazil. Rev Assoc Med Bras 1992; 49(2): 162-6.
[PMID: 12886393]
[PMID: 12886393]
[2]
Ulijaszek S. Obesity: Preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000; 894(4): i-xii, 1-253.
[http://dx.doi.org/10.1017/S0021932003245508] [PMID: 11234459]
[http://dx.doi.org/10.1017/S0021932003245508] [PMID: 11234459]
[3]
Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: National implications for rhythm management and stroke prevention: The AnTicoagulation and risk factors in atrial fibrillation (ATRIA) study. JAMA 2001; 285(18): 2370-5.
[http://dx.doi.org/10.1001/jama.285.18.2370] [PMID: 11343485]
[http://dx.doi.org/10.1001/jama.285.18.2370] [PMID: 11343485]
[4]
Ruddox V, Sandven I, Munkhaugen J, Skattebu J, Edvardsen T, Otterstad JE. Atrial fibrillation and the risk for myocardial infarction, all-cause mortality and heart failure: A systematic review and meta-analysis. Eur J Prev Cardiol 2017; 24(14): 1555-66.
[http://dx.doi.org/10.1177/2047487317715769] [PMID: 28617620]
[http://dx.doi.org/10.1177/2047487317715769] [PMID: 28617620]
[5]
Nalliah CJ, Sanders P, Kottkamp H, Kalman JM. The role of obesity in atrial fibrillation. Eur Heart J 2016; 37(20): 1565-72.
[http://dx.doi.org/10.1093/eurheartj/ehv486] [PMID: 26371114]
[http://dx.doi.org/10.1093/eurheartj/ehv486] [PMID: 26371114]
[6]
Wang TJ, Parise H, Levy D, et al. Obesity and the risk of new-onset atrial fibrillation. JAMA 2004; 292(20): 2471-7.
[http://dx.doi.org/10.1001/jama.292.20.2471] [PMID: 15562125]
[http://dx.doi.org/10.1001/jama.292.20.2471] [PMID: 15562125]
[7]
Huxley RR, Lopez FL, Folsom AR, et al. Absolute and attributable risks of atrial fibrillation in relation to optimal and borderline risk fac-tors: The atherosclerosis risk in communities (ARIC) study. Circulation 2011; 123(14): 1501-8.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.009035] [PMID: 21444879]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.009035] [PMID: 21444879]
[8]
Sandhu RK, Ezekowitz J, Andersson U, et al. The ‘obesity paradox’ in atrial fibrillation: Observations from the ARISTOTLE (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation) trial. Eur Heart J 2016; 37(38): 2869-78.
[http://dx.doi.org/10.1093/eurheartj/ehw124] [PMID: 27071819]
[http://dx.doi.org/10.1093/eurheartj/ehw124] [PMID: 27071819]
[9]
Proietti M, Guiducci E, Cheli P, Lip GY. Is there an obesity paradox for outcomes in atrial fibrillation? A systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulant trials. Stroke 2017; 48(4): 857-66.
[http://dx.doi.org/10.1161/STROKEAHA.116.015984] [PMID: 28265017]
[http://dx.doi.org/10.1161/STROKEAHA.116.015984] [PMID: 28265017]
[10]
Badheka AO, Rathod A, Kizilbash MA, et al. Influence of obesity on outcomes in atrial fibrillation: Yet another obesity paradox. Am J Med 2010; 123(7): 646-51.
[http://dx.doi.org/10.1016/j.amjmed.2009.11.026] [PMID: 20609687]
[http://dx.doi.org/10.1016/j.amjmed.2009.11.026] [PMID: 20609687]
[11]
Pandey A, Gersh BJ, McGuire DK, et al. Association of body mass index with care and outcomes in patients with atrial fibrillation: Re-sults from the ORBIT-AF registry. JACC Clin Electrophysiol 2016; 2(3): 355-63.
[http://dx.doi.org/10.1016/j.jacep.2015.12.001] [PMID: 29766895]
[http://dx.doi.org/10.1016/j.jacep.2015.12.001] [PMID: 29766895]
[12]
Lavie C, Pandey A, Lau D, Alpert M, Sanders P. Obesity and atrial fibrillation prevalence and pathogenesis, and prognosis: Effects of weight loss and exercise. J Am Coll Cardiol 2017; 70(16): 2022-35.
[PMID: 29025560]
[PMID: 29025560]
[13]
Bertomeu-Gonzalez V, Moreno-Arribas J, Esteve-Pastor MA, et al. Association of body mass index with clinical outcomes in patients with atrial fibrillation: A report from the FANTASIIA registry. J Am Heart Assoc 2020; 9(1)e013789
[http://dx.doi.org/10.1161/JAHA.119.013789] [PMID: 31870235]
[http://dx.doi.org/10.1161/JAHA.119.013789] [PMID: 31870235]
[14]
Zhou Y, Ma J, Zhu W. Efficacy and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation across BMI cate-gories: A systematic review and meta-analysis. Am J Cardiovasc Drugs 2020; 20(1): 51-60.
[http://dx.doi.org/10.1007/s40256-019-00362-4] [PMID: 31342343]
[http://dx.doi.org/10.1007/s40256-019-00362-4] [PMID: 31342343]
[15]
Overvad TF, Rasmussen LH, Skjøth F, Overvad K, Lip GYH, Larsen TB. Body mass index and adverse events in patients with incident atrial fibrillation. Am J Med 2013; 126(7): 640.e9-640.e17.
[http://dx.doi.org/10.1016/j.amjmed.2012.11.024] [PMID: 23601271]
[http://dx.doi.org/10.1016/j.amjmed.2012.11.024] [PMID: 23601271]
[16]
Boriani G, Laroche C, Diemberger I, et al. Overweight and obesity in patients with atrial fibrillation: Sex differences in 1-year outcomes in the EORP-AF general pilot registry. J Cardiovasc Electrophysiol 2018; 29(4): 566-72.
[http://dx.doi.org/10.1111/jce.13428] [PMID: 29345382]
[http://dx.doi.org/10.1111/jce.13428] [PMID: 29345382]
[17]
January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: Executive summary: A report of the American college of cardiology/American heart association task force on practice guidelines and the heart rhythm society. Circulation 2014; 130(23): 2071-104.
[http://dx.doi.org/10.1161/CIR.0000000000000040] [PMID: 24682348]
[http://dx.doi.org/10.1161/CIR.0000000000000040] [PMID: 24682348]
[18]
Netley J, Howard K, Wilson W. Effects of body mass index on the safety and effectiveness of direct oral anticoagulants: A retrospective review. J Thromb Thrombolysis 2019; 48(3): 359-65.
[http://dx.doi.org/10.1007/s11239-019-01857-2] [PMID: 30963393]
[http://dx.doi.org/10.1007/s11239-019-01857-2] [PMID: 30963393]
[19]
Malik AH, Yandrapalli S, Shetty S, et al. Impact of weight on the efficacy and safety of direct-acting oral anticoagulants in patients with non-valvular atrial fibrillation: A meta-analysis. Europace 2020; 22(3): 361-7.
[http://dx.doi.org/10.1093/europace/euz361] [PMID: 31985781]
[http://dx.doi.org/10.1093/europace/euz361] [PMID: 31985781]
[20]
Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: Guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14(6): 1308-13.
[http://dx.doi.org/10.1111/jth.13323] [PMID: 27299806]
[http://dx.doi.org/10.1111/jth.13323] [PMID: 27299806]
[21]
Kido K, Shimizu M, Shiga T, Hashiguchi M. Meta-analysis comparing direct oral anticoagulants versus warfarin in morbidly obese patients with atrial fibrillation. Am J Cardiol 2020; 126: 23-8.
[http://dx.doi.org/10.1016/j.amjcard.2020.03.048] [PMID: 32345473]
[http://dx.doi.org/10.1016/j.amjcard.2020.03.048] [PMID: 32345473]
[22]
Proietti M, Lane DA, Lip GY. Relation of nonvalvular atrial fibrillation to body mass index (from the SPORTIF Trials). Am J Cardiol 2016; 118(1): 72-8.
[http://dx.doi.org/10.1016/j.amjcard.2016.04.013] [PMID: 27184172]
[http://dx.doi.org/10.1016/j.amjcard.2016.04.013] [PMID: 27184172]
[23]
Senoo K, Lip GY. Body mass index and adverse outcomes in elderly patients with atrial fibrillation: The AMADEUS trial. Stroke 2016; 47(2): 523-6.
[http://dx.doi.org/10.1161/STROKEAHA.115.011876] [PMID: 26628383]
[http://dx.doi.org/10.1161/STROKEAHA.115.011876] [PMID: 26628383]
[24]
Pokorney SD, Piccini JP, Stevens SR, et al. Cause of death and predictors of all-cause mortality in anticoagulated patients with nonvalvular atrial fibrillation: Data from ROCKET AF. J Am Heart Assoc 2016; 5(3)e002197
[http://dx.doi.org/10.1161/JAHA.115.002197] [PMID: 26955859]
[http://dx.doi.org/10.1161/JAHA.115.002197] [PMID: 26955859]
[25]
Lau DH, Middeldorp ME, Sanders P. Obesity paradox in atrial fibrillation: A distracting reality or fictitious finding? Eur Heart J 2016; 37(38): 2879-81.
[http://dx.doi.org/10.1093/eurheartj/ehw261] [PMID: 27432018]
[http://dx.doi.org/10.1093/eurheartj/ehw261] [PMID: 27432018]
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