Patients with AF and diabetes
This section looks at the epidemiology of diabetes in patients with AF and examines how the presence of diabetes affects prognosis and treatment
In this section:
Atrial fibrillation in patients with diabetes and renal impairment
Preserving renal function is important in patients with atrial fibrillation and diabetes
Approval number PP-XAR-ALL-1379-1
Epidemiology
Diabetes affects an estimated 422 million adults worldwide, or 8.5% of people aged ≥18 years old.1 In patients with AF, diabetes is even more prevalent.2 The global GARFIELD-AF registry shows that 21.7% of patients with AF have co-morbid diabetes, with similar percentages reported in national registries from France, the UK and Italy.2-5 However, an even higher prevalence of diabetes in patients with AF has been identified elsewhere in the world: 29.5% in the USA, 33.7% in Spain and 37.3% in Germany.6-8
The high prevalence of diabetes in patients with AF is cause for concern. Cardiovascular (CV) events – including strokes – are the cause of death in 70% of patients with type 2 diabetes.9 In addition, as shown in a meta-analysis of seven studies, a diagnosis of co-morbid diabetes significantly increases the risk of stroke in patients with AF (RR=1.7; 95% CI 1.4–2.0).10
A worse prognosis was also observed in the GARFIELD AF registry, which found that diabetes in patients with AF was associated with a significant increase in the 2-year risk of stroke/SE (HR=1.23; 95% CI 1.03–1.47) and all-cause mortality (HR=1.27; 95% CI 1.15–1.41) but no increase in the risk of bleeding events (HR=0.92; 95% CI 0.71–1.18).2 On the other hand, although the ORBIT-AF registry showed that the 2-year risk of all-cause death (aged <70 years: HR=1.63; 95% CI 1.04–2.56; aged ≥70 years: HR=1.25; 95% CI 1.09–1.44) and all-cause hospitalization (HR=1.15; 95% CI 1.09–1.22) was increased by a diagnosis of diabetes, the risk of stroke, non-CNS SE and TIA was not (HR=0.98; 95% CI 0.76–1.26).6
As well as worsening AF-related outcomes, diabetes is also the leading cause of chronic kidney disease worldwide and approximately 1 in 3 patients with type 2 diabetes have clinically significant chronic kidney disease.11,12 Importantly, renal function declines twice as quickly in patients with diabetes than it does in patients without diabetes meaning there is less time to take action and prevent the development of an additional serious comorbidity.13 Furthermore, as well as the burden associated with the condition itself, chronic kidney disease is also associated with increased risk of stroke in patients with AF.14,15
Clinical evidence
A large amount of clinical evidence supports the use of the non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban, rivaroxaban) in patients with diabetes. All phase III NOAC trials included a large number of patients with diabetes, although the proportions were different in each trial.16-19
ROCKET AF, which evaluated rivaroxaban, had the largest proportion of patients with diabetes, as well as the overall highest risk population based on CHADS2 score.16-19 In a pre-specified subanalysis of ROCKET AF, rivaroxaban was associated with a significant reduction in the risk of CV death compared with warfarin in patients with diabetes (HR=0.80; 95% CI 0.64–0.99).20 Furthermore, in patients with diabetes, rivaroxaban had similar efficacy to warfarin with respect to prevention of stroke/SE and similar rates of major bleeding.20 In subanalyses of patients with diabetes in ARISTOTLE, apixaban and warfarin had consistent efficacy and safety profiles and no difference in CV death was observed between treatment groups.21 In a subanalysis of RE-LY, there was no evidence for a significant difference in CV death or major bleeding events associated with dabigatran 150 mg bid or dabigatran 110 mg bid compared with warfarin; however, the dabigatran 150 mg bid dose was associated with a significant decrease in the risk of stroke compared with warfarin.22
However, because the phase 3 NOAC trials had different trial designs and recruited different patient populations, it is not possible to make direct comparisons regarding the safety and efficacy of each NOAC.
No diabetes subanalysis has been published for edoxaban.
Evidence supporting the real-world use of rivaroxaban is provided by the XANTUS study, which included 6784 patients with AF receiving rivaroxaban, of whom 19.6% had diabetes.23 XANTUS was a prospective, real-world, phase IV study, which showed that the results of ROCKET AF were reflected in the real world.23 Furthermore, the robust methodology of XANTUS led to its inclusion on the EMA label for rivaroxaban; no real-world evidence is included on the label of any other NOAC.24
Treatment guidelines
ESC guidelines for the management of AF have different recommendations depending on a patients’ CHA2DS2-VASc score.25 Oral anticoagulation is recommended for men with a score ≥2 and women with a score ≥3; oral anticoagulation should be considered in men with a score ≥1 and in women with a score ≥2. In practice, because diabetes and female gender account for a score of 1 each, all patients with diabetes should be at least considered for oral anticoagulation. Oral anticoagulation is recommended in patients with diabetes and one other risk factor, for example, individuals aged ≥65 years old.
In terms of anticoagulant choice, the guidelines are clear: if a patient is eligible for treatment with a NOAC, this is preferred to a VKA, which is only recommended as a first-choice anticoagulant in patients with AF and moderate-to-severe mitral stenosis or mechanical heart valves.25
Guidelines from the ACC/AHA/HRS are similar to those from the ESC.26 However, additional guidance is provided with respect to preserving renal function and suggests that NOACs – particularly rivaroxaban and dabigatran – may be associated with better renal outcomes than warfarin.
The data that this guidance is based on is consistent in patients with diabetes, which,27 taken together with the fact that renal decline is a frequent complication of diabetes, means that this guidance should be considered in these patients.
References
- World Health Organization. Global Report on Diabetes. 2016. Available at: https://www.who.int/diabetes/global-report/en/ [accessed 02 April 2019]. World Health Organization. Global Report on Diabetes. 2016. Available at: https://www.who.int/diabetes/global-report/en/ [accessed 02 April 2019]. Return to content
- Bassand JP, Accetta G, Al Mahmeed W et al. Risk factors for death, stroke, and bleeding in 28,628 patients from the GARFIELD-AF registry: rationale for comprehensive management of atrial fibrillation. PLoS One 2018;13:e0191592. Bassand JP, Accetta G, Al Mahmeed W et al. Risk factors for death, stroke, and bleeding in 28,628 patients from the GARFIELD-AF registry: rationale for comprehensive management of atrial fibrillation. PLoS One 2018;13:e0191592. Return to content
- Shantsila E, Wolff A, Lip GYH, Lane DA. Optimising stroke prevention in patients with atrial fibrillation: application of the GRASP-AF audit tool in a UK general practice cohort. Br J Gen Pract 2015;65:e16–e23. Return to content
- Antonucci E, Poli D, Tosetto A et al. The Italian START-register on anticoagulation with focus on atrial fibrillation. PLoS One 2015;10:e0124719. Return to content
- Maura G, Billionnet C, Drouin J et al. Oral anticoagulation therapy use in patients with atrial fibrillation after the introduction of non-vitamin K antagonist oral anticoagulants: findings from the French healthcare databases, 2011-2016. BMJ Open 2019;9:e026645. Return to content
- Echouffo-Tcheugui JB, Shrader P, Thomas L et al. Care patterns and outcomes in atrial fibrillation patients with and without diabetes: ORBIT-AF registry. J Am Coll Cardiol 2017;70:1325–1335. Echouffo-Tcheugui JB, Shrader P, Thomas L et al. Care patterns and outcomes in atrial fibrillation patients with and without diabetes: ORBIT-AF registry. J Am Coll Cardiol 2017;70:1325–1335. Return to content
- Barrios V, Calderon A, Escobar C, de la Figuera M. Patients with atrial fibrillation in a primary care setting: Val-FAAP study. Rev Esp Cardiol 2012;65:47–53. Return to content
- Collings SL, Lefevre C, Johnson ME et al. Oral anticoagulant persistence in patients with non-valvular atrial fibrillation: A cohort study using primary care data in Germany. PLoS One 2017;12:e0185642. Return to content
- Laakso M. Diabetes Care. 2010;33:442–449. Laakso M. Diabetes Care. 2010;33:442–449. Return to content
- The Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007;69:546–554. The Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007;69:546–554. Return to content
- Jha V, Garcia-Garcia G, Iseki K et al. Chronic kidney disease: global dimension and perspectives. Lancet 2013;382:260-272. Return to content
- New JP, Middleton RJ, Klebe B et al. Assessing the prevalence, monitoring and management of chronic kidney disease in patients with diabetes compared with those without diabetes in general practice. Diabet Med 2007;24:364–369. Return to content
- Sheen YJ, Sheu WH. Risks of rapid decline renal function in patients with type 2 diabetes. World J Diabetes 2014;5:835-846. Return to content
- Jha AK, Larizgoitia I, Audera-Lopez C et al. The global burden of unsafe medical care: analytic modelling of observational studies. BMJ Qual Saf 2013;22:809–815. Return to content
- Olesen JB et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med. 2012;367(7):625-635 Return to content
- Connolly S.J., Ezekowitz M.D., Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. Connolly S.J., Ezekowitz M.D., Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. Return to content
- Granger CB, et al. N Engl J Med. 2011;365:981–992. Granger CB, et al. N Engl J Med. 2011;365:981–992. Return to content
- Giugliano RP, et al. N Engl J Med. 2013;369:2093–2104. Giugliano RP, et al. N Engl J Med. 2013;369:2093–2104. Return to content
- Patel MR, et al. N Engl J Med. 2011;365:883–891. Patel MR, et al. N Engl J Med. 2011;365:883–891. Return to content
- Bansilal S, et al. Am Heart J. 2015;170:675–682.e8. Return to content
- Ezekowitz JA, Lewis B, Lopes R et al. Apixaban compared with warfarin in patients with diabetes and nonvalvular atrial fibrillation in the ARISTOTLE trial. J Am Coll Cardiol 2014;63:A372. Return to content
- Brambatti M, Darius H, Oldgren J et al. Comparison of dabigatran versus warfarin in diabetic patients with atrial fibrillation: Results from the RE-LY trial. Int J Cardiol 2015;196:127–131. Return to content
- Camm AJ, Amarenco P, Haas S et al. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 2016;37:1145–1153. Return to content
- Xarelto® (rivaroxaban). Summary of Product Characteristics. 2019. Available at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf. Xarelto® (rivaroxaban). Summary of Product Characteristics. 2019. Available at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf. Return to content
- Kirchhof P, Benussi S, Kotecha D et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893-2962. Return to content
- January CT, et al. Circulation. 2019;140:e125–e151. Return to content
- Yao X., Tangri N., Gersh B.J. et al. Renal outcomes in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol. 2017;70(21):2621–32. Return to content
See Also
Peripheral Artery Disease: causes and consequences
See Also
Coronary Artery Disease: causes and consequences
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Updated date 10/10/2022
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