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Patients with diabetes and atrial fibrillation: How can the risk of cardiovascular death be reduced?
Patient case: The importance of protecting patients with atrial fibrillation and co-morbid diabetes
Think about the following clinical situation:
- Anne is a 68-year-old retired nurse with two grown-up sons
- She enjoys walking her dog in the local park and playing with her three young grandchildren
- Five years ago, Anne was diagnosed with type II diabetes and has been taking metformin to control her blood sugar level
- After complaining of shortness of breath and palpitations, Anne was referred for an electrocardiogram and was subsequently diagnosed with atrial fibrillation (AF)
Anne was aware that her risk of suffering a cardiovascular (CV) event was high as a person with diabetes. Having been told that her risk has increased further after her diagnosis of AF, she is very concerned.
How can Anne be reassured about her increased risk of suffering a fatal CV event?
Diabetes increases the risk of CV mortality in patients with AF
Anne’s situation is not uncommon and is cause for concern. More than 70% of patients with type II diabetes die from CV events, including strokes.1 Protecting younger patients with AF and co-morbid diabetes, such as Anne, is important, because they are more than twice as likely to suffer from a CV-related death than patients with AF alone.2
The prevalence of diabetes in patients with AF is approximately 30%.2 In patients with AF who have co-morbid diabetes, the risk of stroke is increased 1.7-fold compared with those with AF alone.3 This risk can be reduced with anticoagulation treatment.4 With Anne relying on her doctor for protection against CV events, what is the best treatment option available for her?
What is the best protection for high-risk patients with AF?
The 2016 ESC guidelines for the management of AF recommend that where patients are eligible, non-vitamin K antagonist oral anticoagulants (NOACs) are the first choice of anticoagulant,4 and there is no indication that this should be any different for patients with type II diabetes. Evidence from phase III studies of four NOACs (ROCKET AF for rivaroxaban; ARISTOTLE for apixaban, ENGAGE AF-TIMI 48 for edoxaban; and RE-LY for dabigatran) showed that NOAC treatment reduced stroke rates in patients with AF compared with warfarin.5
Of all the four NOAC studies in AF, the patients in ROCKET AF had the highest overall stroke risk based on mean CHADS2 score.6-9 Furthermore, this study included the highest proportion of patients with diabetes.5 For further discussion on patients with diabetes in the phase III NOAC studies see here.
In the ROCKET AF diabetes subgroup analysis, rivaroxaban was associated with a significant 20% relative risk reduction in CV mortality compared with warfarin in patients with AF and diabetes.6,10
Rivaroxaban reduced the risk of CV death by 20% in patients with AF and diabetes compared with warfarin in ROCKET AF10
Additional evidence for the benefit of rivaroxaban in patients with non-valvular AF and diabetes comes from an administrative claims database, which was consistent with the data from ROCKET AF.11
Patients with AF and co-morbid diabetes benefit from 20 mg rivaroxaban in stroke prevention in the real-world11
Furthermore, in an observational study of patients with both AF and diabetes, rivaroxaban was associated with a significant risk reduction in both major adverse CV events and major adverse limb events in comparison with warfarin.12
The evidence, therefore, supports the use of rivaroxaban treatment for patients like Anne in order to protect against stroke and CV mortality.
Further considerations for patients with AF and diabetes
As discussed in detail here, diabetes and AF are both significant risk factors for renal decline. The rate of renal function decline in patients with diabetes is twice that of those without diabetes.13 However, the 2019 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines state that treatment with NOACs, especially rivaroxaban and dabigatran, may be associated with a reduced risk in adverse renal outcomes in patients with AF in comparison with warfarin over time.14 So when reflecting on the effect of anticoagulant therapy on a patient’s renal function, this may be an important consideration.
Summary
It is essential that patients with AF are protected from strokes, therefore, careful consideration should be taken when prescribing antithrombotic therapy. This is particularly important for patients with type II diabetes, like Anne, who are at a higher risk of suffering from CV events. Phase III studies have shown that NOACs reduce the risk of stroke in patients with AF. However, when treating patients with AF and co-morbid diabetes, it is also important to consider CV mortality and other complications of diabetes, such as decline in renal function over time. This way, Anne can be reassured that her anticoagulation treatment has been chosen to provide her the best protection she needs.
- Laakso M. Cardiovascular disease in type 2 diabetes from population to man to mechanisms: the Kelly West Award Lecture 2008. Diabetes Care 2010;33:442–449. 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
- Stroke Risk in Atrial Fibrillation Working G. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007;69:546–554. 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
- Ruff CT et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014;383:955–962. Return to content
- Patel M.R., Mahaffey K.W., Garg J. et al. Rivaroxaban versus warfarin in non-valvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91. Patel M.R., Mahaffey K.W., Garg J. et al. Rivaroxaban versus warfarin in non-valvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91. Return to content
- Granger C.B., Alexander J.H., McMurray J.J. et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92. Return to content
- Giugliano R.P., Ruff C.T., Braunwald E. et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–2104. 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
- Bansilal S, Bloomgarden Z, Halperin JL et al. Efficacy and safety of rivaroxaban in patients with diabetes and nonvalvular atrial fibrillation: The Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF Trial). Am Heart J 2015;170:675–682. Return to content
- Coleman CI, Bunz TJ, Eriksson D et al. Effectiveness and safety of rivaroxaban vs warfarin in people with non-valvular atrial fibrillation and diabetes: an administrative claims database analysis. Diabet Med 2018;35:1105–1110. Return to content
- Baker WL, Beyer-Westendorf J, Bunz TJ et al. Effectiveness and safety of rivaroxaban and warfarin for prevention of major adverse cardiovascular or limb events in patients with non-valvular atrial fibrillation and type 2 diabetes. Diabetes Obes Metab 2019;21:2107–2114. Return to content
- Hemmelgarn BR, Zhang J, Manns BJ et al. Progression of kidney dysfunction in the community-dwelling elderly. Kidney Int 2006;69:2155–2161. Return to content
- January CT, Wann LS, Calkins H et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons. Circulation 2019;140:e125–e151. Return to content
See Also
Thrombosis Adviser at the European Society of Cardiology Congress 2020
See Also
Managing anticoagulation during the COVID-19 pandemic
See Also
Keeping it simple: Single drug approaches to VTE treatment
See Also
Keeping it simple: Single drug approaches to VTE treatment
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Updated date 10/10/2022
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