Obesity paradox in AF patients

The ‘obesity paradox’ in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial

Literature - Sandhu RK et al., Eur Heart J 2016

Sandhu RK, Ezekowitz J, Andersson U, et al.
Eur Heart J 2016;published online ahead of print


BMI is an established risk factor for the development of atrial fibrillation (AF) and an independent predictor of progression from paroxysmal to sustained forms of AF [1,2]. However, the prognostic impact of obesity on clinical outcomes among patients with AF is unclear, since there are data showing that an overweight status and obesity may be associated with a favourable prognosis in patients with CVD [3,4].
This ‘obesity paradox’ has not been studied thoroughly in AF patients, but data show that:
  • overweight status and obesity were associated with a lower risk of death from any cause or CV mortality compared with normal weight [5,6].
  • overweight AF patients had a higher survival rate compared with underweight (BMI 18.5 kg/m2) and normal weight (BMI 18.5–24 kg/m2) patients [7].
  • overweight status and obesity were associated with a higher risk of a composite endpoint (ischemic stroke, thromboembolism, or death) after adjustment [8].
  • there was no association between obesity and risk of thromboembolic events [9].

In this study, the association between various measures of adiposity [BMI and waist circumference (WC)] and clinical outcomes was evaluated in 18,107 participants randomised to apixaban or warfarin in the ARISTOTLE  trial. The clinical outcomes included stroke or systemic embolism (SE), a composite endpoint (stroke, SE, myocardial infarction, or all-cause mortality), all-cause mortality, and major bleeding.

Main results

In multivariable analyses, compared with normal BMI, a higher BMI was associated with: 
  • a lower risk of all-cause mortality: overweight HR: 0.67; 95% CI: 0.59–0.78; obese HR: 0.63; 95% CI: 0.54–0.74; P < 0.0001
  • a lower risk of the composite endpoint: overweight HR: 0.74; 95% CI: 0.65–0.84; obese HR: 0.68; 95% CI: 0.60–0.78; P < 0.0001
With a BMI of 35 to < 40 kg/m2 in adjusted models, there was a lower risk for:  
  • stroke or SE: HR: 0.60; 95% CI: 0.39–0.92
  • death: HR: 0.57; 95% CI: 0.45–0.73
  • composite endpoint: HR: 0.61; 95% CI: 0.49–0.75
 In women, but not in men, high WC was associated with a:
  • 31% lower risk of all-cause mortality (P = 0.001)
  • 27% lower risk of the composite endpoint (P = 0.001)
  • 28% lower risk of stroke or SE (P = 0.048)
In sensitivity analysis using ethnic-specific cut-points, the effect among women regarding stroke or SE (HR: 0.95; 95% CI: 0.63–1.44; P = 0.82) and the composite endpoint (HR: 0.78; 95% CI: 0.62–1.00; P = 0.053) were no longer significant.

Effects of apixaban treatment:
  • Patients treated with apixaban had lower rates of both the efficacy and safety outcomes across all categories of BMI compared with patients treated with warfarin
  • There was a statistically significant interaction (P-interaction = 0.01) between BMI and the effects of apixaban compared with warfarin concerning major bleeding, with a larger reduction in bleeding with normal vs. higher BMI


Prospective data showed that in patients with AF treated with oral anticoagulants, higher BMI and WC are associated with a more favourable prognosis. Adiposity, as measured by BMI or WC did not affect the efficacy of apixaban in these anticoagulated patients, but the reduction obtained with apixaban in major bleeding may be reduced at higher vs. normal BMI.

Find this article online at Eur Heart J


1. Wang TJ, Parise H, Levy D, et al. Obesity and the risk of new-onset atrial fibrillation. JAMA 2004;292:2471–2477
2. Wanahita N, Messerli FH, Bangalore S, et al. Atrial fibrillation and obesity—results of a meta-analysis. Am Heart J 2008;155:310–315
3. Uretsky S, Messerli FH, Bangalore S, et al. Obesity paradox in patients with hypertension and coronary artery disease. Am J Med 2007;120:863–870
4. Wang ZJ, Zhou YJ, Galper BZ, et al. Association of body mass index with mortality and cardiovascular events for patients with coronary artery disease: a systematic review and meta-analysis. Heart 2015;101:1631–1638
5. Badheka AO, Rathod A, Kizilbash MA, et al. Influence of obesity on outcomes in atrial fibrillation: yet another obesity paradox. Am J Med 2010;123:646–651
6. Ardestani A, Hoffman HJ, Cooper HA. Obesity and outcomes among patients with established atrial fibrillation. Am J Cardiol 2010;106:369–373
7. Wang J, Yang YM, Zhu J, et al. Overweight is associated with improved survival and outcomes in patients with atrial fibrillation. Clin Res Cardiol 2014;103:533–542
8. Overvad TF, Rasmussen LH, Skjoth F, et al. Body mass index and adverse events in patients with incident atrial fibrillation. Am J Med 2013;126:640.e9–640.e17
9. Novo G, Mansueto P, La Franca ML, et al. Risk factors, atrial fibrillation and thromboembolic events. Int Angiol 2008;27:433–438

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