Disclosures. LF: consultant or speaker fees of small amounts for AstraZeneca, Bayer, BMS/Pfizer, Boehringer Ingelheim, Medtronic, Novartis, Novo, and Zoll outside of this work.
Key points
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Opportunistic screening for AF by assessing the pulse and heart rate or by ECG recording is appropriate in persons ≥65 years of age and this needs to be carefully applied in persons with diabetes in view of their risk.
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Systematic screening with ECG should be considered to detect AF in persons ≥75 years of age or those at a high risk of stroke, and this deserves specific consideration in persons with diabetes in view of their risk.
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Oral anticoagulation is indicated for stroke prevention in AF persons with DM and with at least one additional (CHA 2 DS 2 -VASc) risk factor for stroke.
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Oral anticoagulation should be considered for stroke prevention in persons with DM and AF and no other risk factors for stroke (according to CHA 2 DS 2 -VASc), particularly in the case of inadequate chronic glycemic control.
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For stroke prevention in persons with AF with DM, DOACs should be preferred over vitamin K antagonists, with the exception of persons with mechanical valve prostheses or mild-to-moderate mitral stenosis.
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The HAS-BLED score helps identify modifiable and nonmodifiable risk factors for bleeding in persons with DM and AF and identify persons in need of closer follow-up.
INTRODUCTION
Atrial fibrillation (AF) and type 2 diabetes mellitus (DM) have emerged as global epidemics worldwide with significant effects on morbidity and mortality. The risk for thromboembolism is higher when AF and DM coexist. In the last decade, there have been significant improvements for stroke prevention in persons with AF with direct oral anticoagulants (DOACs), earlier detection of AF in at-risk populations, and for treating DM with noninsulin antihyperglycemic medications.
Diabetes As a Risk Factor for Atrial Fibrillation
Prevalence and Incidence of Atrial Fibrillation in Persons With Type 2 Diabetes Mellitus
AF is common in persons with DM. The prevalence of AF is around twofold higher in persons with DM compared with persons without DM. AF incidence may be even higher in persons with microvascular complications (kidney disease, retinopathy). In a meta-analysis by Huxley et al. , including prospective studies and case-control studies comprising data from 1.7 million persons, 109,000 of them had incident AF, and DM was associated with about 40% higher risk of AF. However, after adjusting for possible confounding factors, the effect appeared to be more limited with a risk only 24% higher. The proportion of AF attributable to DM in the population was estimated to be only 2.5%. Persons with both T2DM and high blood pressure may have a threefold higher risk of associated AF compared with persons without DM or hypertension, but this association was no longer significant after adjusting for presence of insulin resistance, which therefore appeared to be a major determinant for the development of AF. Insulin resistance is also a mechanism by which hypertension and obesity might be associated with an increased risk of AF. DM and glucose intolerance are also associated with an increased risk of left ventricular hypertrophy (LVH), which could be one of the factors promoting AF. Long-term inflammation is also a suspected link between DM and AF: inflammation may be found in the two conditions, it can partly predict the development of DM and of AF, and antiinflammatory treatments have shown to be efficient on a few indirect parameters for some persons with DM and/or with AF ( Fig. 24.1 ).
Pathophysiology of possible links between diabetes, atrial fibrillation, heart failure, and thromboembolic events. CV , cardiovascular; HF , heart failure.
In a subsequent analysis carried out in 35,000 healthcare professionals and followed for 16 years, females with T2DM had a doubled risk of developing AF during follow-up, but the attributable risk of DM was quite lower (15%) after adjusting for possible confounding factors from the baseline characteristics.
In a study about the risk for AF in T2DM, 421,855 persons with T2DM from the Swedish National Diabetes Register and 2,131,223 controls from the Swedish Population Registry were studied and followed for 13 years. In the fully adjusted risk regression model, the risk of incident AF was 28% greater with T2DM versus controls (HR, 1.28; 95% CI, 1.26–1.30; p < 0.0001). The risk of AF in persons with T2DM increased with poor glycemic control and kidney complications.
Although males usually have higher absolute rates for incident AF, the relative rates of incident AF associated with T2DM are higher in females than in males, and the excess risk in females is mainly seen in middle-aged persons.
This suggests that persons with T2DM have a higher risk of prevalent AF (around 15%) and then of incident AF (around 0.8%/year), which seems in part related to some other associated risk factors commonly seen in these persons. Persons with type 1 are also at a higher risk of AF (HR 1.32 in females vs. males), suggesting that DM per se would also be an independent risk factor for AF. By contrast, when assessing for AF after a stroke, since DM may be more closely associated with noncardioembolic ischemic stroke, the evaluation may not find as much AF.
T2DM has been associated with atrial electrical and structural remodeling that may underlie increased vulnerability for AF. In persons with T2DM, calcium handling may be altered and may further result in AF mediation. Furthermore, atrial fibroblasts from persons with T2DM have a more profibrotic phenotype compared with fibroblasts of persons without DM, evident from increased expression of collagen type 1, which adds to structural remodeling of the atrium.
Therapy for Diabetes Mellitus and Risk of Atrial Fibrillation
The risk of new-onset AF is sometimes associated with diabetes duration and glycemic control ( Fig. 24.2 ) and may be affected by specific antihyperglycemic therapies. The impact of antihyperglycemic therapy on the risk for AF has been discussed in recent years ( Table 24.1 ). While some glucose-lowering therapies decrease the incidence of heart failure (HF) and chronic kidney disease (CKD) in persons with DM, in many cardiovascular outcome studies, AF was not a prespecified outcome. It has been reported that metformin and pioglitazone may be associated with a lower risk for AF. In the DECLARE TIMI-58 trial, dapagliflozin reduced the risk of AF events by 19% (HR, 0.81; 95% CI, 0.68–0.95; p = 0.009). The risk reduction for AF events was consistent regardless of a history of previous AF or cardiovascular disease at baseline. In a meta-analysis of 34 randomized studies, SGLT2i were also associated with 19% lower risk of incident AF in persons with DM or HF. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have been investigated in various populations with an increased cardiovascular risk, but only a few studies reported effects on new onset of AF, with no significant differences when using GLP1-RA.
Effect of duration of diabetes and glycemic control on risk of atrial fibrillation ( AF ). CI , Confidence interval.
Adapted from Dublin S, Glazer NL, Smith NL, et al. Diabetes mellitus, glycemic control, and risk of atrial fibrillation. J Gen Intern Med . 2010;25:853–858.
Table 24.1
Selected Studies Over Time About Glucose-Lowering Drugs Use and Incident Atrial Fibrillation
| FIRST AUTHOR, YEAR | STUDY DESIGN | PATIENTS, N | MEDICATION | FINDINGS |
|---|---|---|---|---|
| Chao et al., 2012 | Cohort | 12,065 | Thiazolidinedione | Lower risk of new-onset AF with thiazolidinediones use vs. nonuse (HR, 0.69; 95% CI, 0.49–0.91; p = 0.03) |
| Chang et al., 2014 | Cohort | 645,710 | Metformin | Lower risk of new-onset AF with metformin use (HR, 0.81; 95% CI, 0.76–0.86; p < 0.0001) |
| Chen et al., 2017 | Case-control | 9790 | Antihyperglycemic agents | Higher risk of AF in insulin users (vs. nonusers; OR, 1.58; 95% CI 1.37–1.82). Lower risk of AF in dipeptidyl peptidase-4 inhibitors users (vs. nonusers; OR, 0.65; 95% CI, 0.45–0.93) |
| Zhang et al., 2017 | Meta-analysis | 130,854 | Thiazolidinedione | Lower risk of AF with thiazolidinedione compared to controls in observational studies (OR, 0.73; 95% CI 0.62–0.87; p = 0.0003) |
| Chang et al., 2017 | Cohort | 90,880 | DPP4i | DPP4i use associated with a lower risk of new-onset AF compared with nonuse (HR, 0.65; p < 0.0001) |
| Monami et al., 2017 | Meta-analysis | 33,271 | GLP1-RA | No association with AF incidence (OR, 0.87; 95% CI 0.71–1.05; p = 0.15) |
| Liou et al., 2018 | Case-control | 14,410 | Antihyperglycemic agents | Higher risk of developing AF in insulin users vs. nonusers (OR, 1.19; 95% CI, 1.06–1.35). Lower risk of AF in biguanides users (OR, 0.81; 95% CI, 0.71–0.95) and thiazolidinediones users (OR, 0.72; 95% CI, 0.63–0.83) vs. nonusers |
| Usman et al., 2018 | Meta-analysis | 34,987 | SGLT2i | Lower risk of AF with SGLT2i use (OR, 0.61; 95% CI, 0.31–1.19; p = 0.15) |
| Zelniker et al., 2020 | RCT | 17,160 | SGLT2i | Lower risk of AF with SGLT2i use (HR, 0.81; 95% CI 0.68–0.95; p = 0.009) |
| Fernandes et al., 2021 | Meta-analysis | 63,166 | SGLT2i | Lower risk of incident atrial arrhythmias with SGLT2i use (OR, 0.81; 95% CI, 0.69–0.95; p = 0.008) |
| Lee et al., 2022 | Cohort | 43,426 |
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Lower risk of incident AF with SGLT2i compared to DPP4i use (HR, 0.68; 95% CI, 0.56–0.83; p = 0.0001) |
| Engström et al., 2023 | Cohort | 136,956 |
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Lower risk of AF with SGLT2i compared to GLP1-RA use (adjusted HR, 0.89; 95% CI, 0.81–0.96) |
| Fawzy et al., 2023 | Cohort | 262,376 | SGLT2i | Lower risk of incident AF with SGLT2i use vs. nonuse (HR, 0.81; 95% CI, 0.76–0.84) |
AF, Atrial fibrillation; CI, confidence interval; DPP-4, dipeptidyl peptidase-4; GLP-1RA, glucagon-like peptide-1 receptor antagonist; HR, hazard ratio; OR, odds ratio; RCT, randomized control trial; SGLT2i, sodium-glucose cotransporter-2 inhibitors.
Screening for Atrial Fibrillation in Diabetes
Considering the high prevalence of AF in T2DM and the estimated incidence of nearly 1%/year, more efficient screening of persons with T2DM for AF might be associated with improved therapeutic management. For symptomatic persons with palpitations (or possibly fatigue and dyspnea) related to persistent or permanent AF, the diagnosis is likely to be made during an outpatient visit or in the hospital if the patient presents emergently. However, AF may also be asymptomatic in 30% to 50% of cases, as mentioned above. It can be found in different ways: on a conventional 12-lead electrocardiogram at a routine consultation or in the hospital, on a 24-hour (sometimes 72-hour) ambulatory ECG recording, or in a patient with a pacemaker or a defibrillator by analyzing the diagnostic functions (serving as long-term ambulatory ECG) during a check in-office or during remote monitoring or by wearable technology that assess heart rate and rhythm. Subcutaneously implantable loop recorders with long-term information over 24 to 36 months have the technical capacity to diagnose AF independent of symptoms, but their use is only approved in most countries for the evaluation of persons with unexplained syncope or for those with ischemic stroke and no documented AF. AF detection with an implantable loop recorder in persons with DM may have a similar clinical impact regarding the need for oral anticoagulation. Also, AF may currently be detected by consumer devices and wearables detecting an irregular pulse (e.g., photoplethysmography). In these cases, there is a need for a definite diagnosis of AF by a direct recording of an ECG tracing (e.g., using the recent version of smartwatches).
Potential advantages and disadvantages of detecting undiagnosed AF through screening have been identified. Specific recommendations on strategies and tools for routine screening of AF in persons with DM who are asymptomatic might be included in future guidelines, since data are consistent on two points:
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When T2DM is associated with other risk factors (more particularly when the CHA 2 DS 2 -VASc score is high), the risk of developing AF increases during follow-up and may reach nearly 20% per year in some very-high-risk subgroups.
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At the same time, the annual thromboembolic risk increases exponentially in these persons in the case of AF and can reach 8% to 10% per year.
It would seem logical on a population scale to systematically screen for AF in persons without AF with a CHA 2 DS 2 -VASc score of 2 or higher to identify subclinical AF that would inform therapy to reduce the risk of stroke, which is the major complication in this setting. This approach has not been validated in a specific randomized study dedicated to persons with T2DM. The ESC guidelines for the management of AF currently recommend opportunistic screening for any patient over 65 years and systematic screening for persons at high risk of developing AF. Thus both opportunistic and systematic screenings for AF in persons with diabetes are appropriate, and this may include using a prolonged noninvasive ECG-based approach and should be considered in individuals aged ≥65 years with diabetes to ensure earlier detection of AF.
The association between AF and DM appears to be well established at the population level. DM associated with AF result in a worse prognosis, and several reports from health authorities indicate that efforts must be made for the prevention of AF, although there is not a strong level of evidence that this strategy will result in a significant benefit regarding morbidity (particularly ischemic stroke) or mortality.
Diabetes as a Risk Factor for Worse Prognosis in Persons With Atrial Fibrillation
DM and AF frequently coexist, and when this occurs, there is a substantially higher risk of all-cause death, cardiovascular death, stroke, CKD, and HF. The risk of death may be 25% to 60% higher in persons with AF with DM (vs. AF and no DM). Risk factors frequently associated with DM, such as hypertension and obesity, may also worsen prognosis. The association of DM and kidney impairment is associated with a higher risk of cardiovascular events and mortality than each condition alone, emphasizing the role of cardiovascular prevention in persons with T2DM when AF is also present. AF is associated with higher risks and cardiovascular events in persons with T2DM, strongly suggesting that AF further increases the already elevated cardiovascular risk in these persons. AF identifies persons with DM likely to obtain greater absolute benefits from efficient blood pressure-lowering treatment. AF in persons with T2DM should be considered as a marker of adverse outcome, suggesting prompt and aggressive management of all risk factors.
The detection of AF in persons with DM has major clinical consequences because the risk of stroke is markedly higher in these persons. In the absence of other comorbidities, the annual risk of stroke can be estimated at 2.2% per year in isolated DM. It is also higher in persons with diabetes due to the common association with other risk factors for stroke, including the existence of hypertension, an age over 65 or 75, associated vascular disease, or HF. All of them are identified in the items of the CHA 2 DS 2 -VASc score. Although there may be some disparities in the literature, several analyses reported that the presence of DM was an independent predictor for ischemic stroke in persons with AF. However, the incremental risk for stroke in older persons associated with DM is attenuated, most likely due to a contributing risk of comorbidities. Overall, DM is probably not the most potent independent risk factor for stroke in AF compared with the other items in the CHA 2 DS 2 -VASc score widely used to guide anticoagulation therapy, but it is included in this risk stratification tool, giving a point as well as for most other items.
Beyond the higher risk of mortality and cardiovascular events, DM in persons with AF is likely to modify symptoms, particularly breathlessness, which is linked to the higher prevalence of obesity and higher risk of HF. However, one part of the adverse influence of DM in persons with AF might be sometimes related to a masking of AF-related palpitations, which can cause a delay in the initiation of treatment and consequently poorer outcomes in persons with T2DM. Compared with persons with AF with no DM, those with DM less often reported palpitations (29% vs. 34%) or syncope (3% vs. 5%), but they reported significantly more frequent dyspnea on exertion (30% vs. 27%) or at rest (11% vs. 10%), exercise intolerance (12% vs. 9%), and fatigue (28% vs. 26%). Although these differences were statistically significant, they may not be apparent from a clinical point of view. Persons with AF with DM had worse functional status with higher European Heart Rhythm Association scores (although the percent of persons with no symptoms was similar) and also had marginally lower quality-of-life scores than those with no DM. DM has also been identified as an independent predictor of AF recurrence after AF ablation. While AF ablation usually reduces palpitations and improves NYHA functional class in persons without DM, persons with DM may report less improvement of NYHA class, despite a reduction of palpitations ( Table 24.2 ).
Table 24.2
Studies on Diabetes and Outcomes After Catheter Ablation of Atrial Fibrillation (AF)
| FIRST AUTHOR, YEAR | STUDY DESIGN | PATIENTS, N (DM) | FINDINGS |
|---|---|---|---|
| Tang et al., 2006 | Cohort | 263 (31) | No difference in AF recurrence between DM and non-DM patients after the procedure (mean follow-up of 13 months, 32.3% vs. 22.4%; p = 0.24) |
| Chao et al., 2010 | Cohort | 228 (65) | Abnormal glucose metabolism associated with increased postablation AF recurrence (mean follow-up of 19 months, 18.5% vs. 8.0%; HR, 3.25; 95% CI, 1.21–8.72; p = 0.02) |
| Wokhlu et al., 2010 | Cohort | 774 (47) | Diabetes independent predictor of AF recurrence (median follow-up of 3.0 years; HR, 1.9; 95% CI, 1.3–2.9; p = 0.002) |
| Lin et al., 2014 | Meta-analysis | 12,924 (N/A) | No difference in postablation AF recurrence between DM and non-DM patients (OR, 1.11; 95% CI, 0.97–1.26) |
| Anselmino et al., 2015 | Meta-analysis | 1464 (1464) | Higher HbA1c, older age, higher BMI, related to higher risk of AF recurrence ( p < 0.001) |
| Bogossian et al., 2016 | Cohort | 8175 (944) | No increased periprocedural risk and no increased arrhythmia recurrence after ablation of atrial flutter or AF. Reduced palpitations with ablation in both DM and no DM. Improved NYHA class only in patients with no DM |
| Donnellan et al., 2019 | Cohort | 298 (298) | Higher HbA1c at the time of ablation associated with higher postablation AF recurrence rates (69% if HbA1c > 9% vs. 32% if HbA1c < 7%; P < 0.0001) |
| Creta et al., 2020 | Cohort | 2504 (234) | DM associated with higher rate of atrial arrhythmia relapse (32% vs. 25%; p = 0.03), particularly for patients with persistent AF |
| Zhao et al., 2023 | Cohort | 525 (525) | Lower risk of AF recurrence after AF ablation with SGLT2i use among patients with DM (HR, 0.63; 95% CI, 0.44–0.90; p = 0.007) |
| Abu-Qaoud et al., 2023 | Cohort | 4450 (4450) | Lower risk of arrhythmia recurrence after AF ablation with SGLT2i use among patients with DM (HR, 0.85; 95% CI, 0.77–0.95; p = 0.003) |
AF, Atrial fibrillation; CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio; OR, odds ratio; SGLT2i, sodium-glucose cotransporter-2 inhibitors.
CARDIOVASCULAR COMPLICATIONS AND RISK OF STROKE IN ATRIAL FIBRILLATION WITH DIABETES
The Risk of Cardiovascular Complications When Diabetes and Atrial Fibrillation Coexist
Type 2 DM is linked to lifestyle and is therefore usually associated with additional cardiovascular risk factors for stroke such as obesity, hypertension, and dyslipidemia, creating a complex interaction of adverse effects with an increased risk of cerebrovascular events. In epidemiological studies performed in different populations, the relative risk of stroke in DM ranged between 1.4 and 5.8, being 2.5 for males and 3.6 for females in the 20-year follow-up of the cohort of the historical Framingham study, aged 30 to 62 years at study entry.
The patterns of strokes associated with T2DM may be different from those of cardioembolic strokes related to AF, since most of the ischemic strokes in persons with T2DM correspond to lacunar infarcts, related to microvascular disease and the coexistence of hypertension. Moreover, the strokes associated with DM are associated with a higher risk of mortality, as well as more stroke recurrences and stroke-related dementia as compared with non-diabetic patients.
Considering the interactions between AF and DM (around 15% of persons with DM presenting with AF according to data from a meta-analysis on T2DM and around 30% of persons with AF affected by DM), it may be challenging to assess the effects of T2DM control and antihyperglycemic medications on the risk of stroke in persons with AF. There is controversy on whether better glycemic control results affect stroke rates in persons with DM. A longer duration of DM has been associated with an increased risk of embolic stroke but was not associated with a higher risk of bleeding during anticoagulant treatment. In an analysis of a group of persons enrolled in the ATRIA (Anticoagulation and Risk Factors in AF) study, focusing on periods where persons were not anticoagulated, a longer duration of DM was associated with an increased rate of ischemic stroke. The analyses regarding the relationship between the magnitude of increased HbA1c and the risk of ischemic stroke in persons with AF with DM resulted in conflicting results.
Beyond the level of glycemic control, analyses from the PREFER in AF (European Prevention of Thromboembolic Events–European Registry in AF) study showed that the risk of stroke was higher in individuals with DM treated with insulin compared with those not treated with insulin and to persons with no DM. Whether this association reflects a causal effect or a clustering of risk factors and long DM duration in persons treated with insulin compared with other glucose-lowering agents is not clear. Apart from insulin, the effects of other medications for glycemic control on stroke risk are still objects of investigation, with a lower risk of stroke when using metformin and thiazolidinediones.
Beyond stroke, DM is associated with worse outcomes in persons with AF enrolled in contemporary registries. In interpreting these associations, the higher prevalence of persistent and permanent AF, as well as the higher prevalence of HF, CKD, and coronary artery disease (CAD) among persons with DM, has to be considered. The worst profile of persons with T2DM and AF was also reported in the EORP-AF (EURObservational Research Program Atrial Fibrillation) General Registry, where persons with DM had a higher prevalence of most comorbidities and a higher risk of all-cause, cardiovascular, and noncardiovascular mortality. The reciprocal relationship was also found in persons with DM, in whom AF was associated with worse outcomes. In the ADVANCE study, persons with diabetes with AF had increased risks of major coronary events, stroke, HF, cardiovascular death, and all-cause mortality compared with persons with T2 DM without AF.
Diabetic retinopathy is a typical microvascular complication of DM, and in the Loire Valley AF project, crude rates of stroke/thromboembolism increased in a stepwise fashion when persons with AF and no DM were compared with persons with AF with DM with no retinopathy and persons with AF with DM and retinopathy. However, the presence of retinopathy associated with DM was not an independent predictor for stroke or severe bleeding in multivariable analyses.
Diabetes Subtypes, Diabetes Severity, and the Risk of Cardiovascular Events in Atrial Fibrillation
DM is a heterogeneous chronic metabolic disease that is characterized by hyperglycemia that may be caused by several different mechanisms, such as low insulin production and/or decreased insulin sensitivity. Compared with T1DM (10%–15% of cases) usually seen in younger persons and characterized by a lack of insulin production that is associated with autoimmunity, T2DM (80%–85% of cases) has an older age of onset and is characterized by abnormally high circulating insulin-to-glucose ratio and high levels of Homeostatic Model Assessment of Insulin Resistance (HOAM-IR) that are closely associated with central obesity-related insulin resistance. Furthermore, additional rare forms of DM exist, which often have a genetic background, such as maturity-onset DM of the young (MODY) and neonatal DM.
When applying the CHA 2 DS 2 -VASc score to assess the risk for a stroke in AF, the “D” (diabetes) is defined as fasting blood glucose ≥7 mmol/L (or ≥126 mg/dL) or treatment with oral antihyperglycemic medications and/or insulin. In addition to the different DM types, DM may have heterogeneous and different degrees of target organ damage for eyes, nerves, and kidneys, which may also affect the risk for cardiovascular complications. The risk for stroke in persons with DM and AF increases with longer DM duration, as well as with more DM comorbidities such as nephropathy and retinopathy.
The characterization of DM types may actually be more complex. In 8980 adults with newly diagnosed DM, Ahlqvist et al. identified five patient clusters based on six preselected parameters: age at diagnosis, body mass index (BMI), absence or presence of glutamate decarboxylase antibodies identifying autoimmune DM, HbA1c levels for assessment of glycemic control, Homeostatic Model Assessment 2 (HOMA2)-B to assess β-cell function on the basis of C-peptide and glucose concentration, and HOMA2-IR to assess insulin sensitivity. The severe, insulin-resistant diabetes (SIRD) cluster had the highest risk of coronary events (HR, 1.76; 95% CI, 1.36–2.27) and stroke (HR, 1.72; 95% CI, 1.20–2.48) compared with the mild age-related diabetes (MARD) cluster, but the relevance in the context of AF for the risk of stroke is unknown.
ANTICOAGULATION IN PERSONS WITH DIABETES AND ATRIAL FIBRILLATION
Treatment with an oral anticoagulant of persons with AF at high risk of stroke leads to a substantial reduction in stroke and systemic embolism (SE). The original data concerned vitamin K antagonists (VKAs). It is today fully established that the efficacy of anticoagulant therapy is far superior than antiplatelet therapy for stroke prevention in AF. Oral anticoagulation is the main part in the “A” pillar of the “ABC” AF management (“A,” Anticoagulation/Avoid stroke).
Persons with AF can be stratified according to their risk for stroke and systemic embolism. The preferred cardioembolic risk stratification tool is the CHA 2 DS 2 -VASc score, specifically for excluding from anticoagulation those persons at very low risk of stroke. The CHA 2 DS 2 -VA score (excluding sex category for simplicity) is proposed in the most recent European guidelines to decide the initiation of long-term anticoagulation. These scoring systems include DM as a risk factor for stroke because the likelihood of developing a thromboembolic event is substantially increased in persons with diabetes with AF. The use of VKAs in persons with DM is effective in reducing strokes and systemic embolism, but anticoagulation control may be more difficult to obtain than in persons without diabetes, and adverse bleeding events may be more frequent in persons with T2DM.
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