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Peripheral Artery Disease: causes and consequences

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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

Atrial fibrillation in patients with diabetes and renal impairment

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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

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

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Prevalence of diabetes in patients with AF.2-8

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

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Comparison of outcomes in patients with or without diabetes.2,6,10

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 

 

More information on the importance of preserving renal function in patients with diabetes and AF can be found here.

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

Patient characteristics in the phase III NOAC studies.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.

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Outcomes in subanalyses of patients with diabetes in phase III NOAC studies for rivaroxaban (A), apixaban (B) and dabigatran (C).20-22 Data are not intended for direct comparison between NOACs.

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

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.

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Treatment of patients with AF and diabetes according to the 2016 ESC guidelines and the 2019 ACC/AHA/HRS guidelines.25,26

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.

 

More information on the relationship between diabetes and renal impairment in patients with AF can be found here.

References

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