Does the presence of diabetes mellitus confer an increased risk of stroke in patients with atrial fibrillation on direct oral anticoagulants? A systematic review and meta-analysis

Abdool, Mohammad; Kunutsor, Setor K; Khunti, Kamlesh; Seidu, Samuel

doi:10.1016/j.dsx.2020.08.038

Cited by 7 publications

(5 citation statements)

References 46 publications

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“…An important cause of stroke is atrial fibrillation, and in a study of this relationship, persons with diabetes, although more likely to be anticoagulated with warfarin than nondiabetic persons with atrial fibrillation, had greater risk of stroke, although with improvement during the period from 1992 to 2019 24 . A meta‐analysis of studies of atrial fibrillation showed that those with diabetes had greater risk of stroke as well as of other vascular events and of mortality, with similar risk reduction comparing warfarin with direct oral anticoagulants 25 …”

Section: The Association Of Diabetes With Strokementioning

confidence: 97%

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Diabetes and stroke: An important complication

Bloomgarden

Chilton

2020

Journal of Diabetes

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Diabetes is associated with a plethora of metabolic changes which may underlie the propensity to development of stroke (Figure 1). 1 Insulin resistance has multiple drivers, is inextricably linked to type 2 diabetes, and is associated with coronary artery 2 and cerebrovascular 3 atherosclerosis. Insulin resistance is mediated by increased levels of bioactive lipids, including ceramides 4 and diacylglycerol, 5 playing a role in cell death in numerous tissues. 6 Hyperglycemia leads to formation of advanced glycation end products and to activation of the polyol pathway, protein kinase C pathway, and the polyadenosine diphosphate-ribose polymerase (PARP) and hexosamine pathways, all increasing oxidative stress, with formation of such reactive oxygen species as the hydroxyl radical, superoxide anion, peroxides, reducing endogenous antioxidants including superoxide dismutase, glutathione, and ascorbic acid and eventuating in oxidative damage of DNA, proteins, and lipids, causing cellular necrosis or apoptosis. 1 Hyperglycemia directly and indirectly increases circulating levels of T cells and macrophages as well as inflammatory and prothrombotic factors, reduces endothelial function, and leads to glycation and oxidation of lipoproteins, increasing their atherogenicity. 1 A specific mediator of oxidative stress involves activation of the transient receptor potential melastatin (TRMP) 2 calcium channel by ischemia/reperfusion injury, a pathway upregulated in diabetes and insulin-resistant states and mediating neuronal cell death in association with oxidative stress. 7 Diabetes leads to reductions in levels of key microRNAs, miRNA-126, miRNA-124, and miRNA-223, which are also downregulated in stroke and which have anti-inflammatory and neuroprotective effects. 8

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Section: The Association Of Diabetes With Strokementioning

confidence: 97%

“…24 A meta-analysis of studies of atrial fibrillation showed that those with diabetes had greater risk of stroke as well as of other vascular events and of mortality, with similar risk reduction comparing warfarin with direct oral anticoagulants. 25…”

Section: The Association Of Diabetes With Strokementioning

confidence: 99%

Diabetes and stroke: An important complication

Bloomgarden

Chilton

2020

Journal of Diabetes

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“…The healthcare burden of atrial fibrillation is increasing because of the accelerated aging of the population worldwide ( 2 ). Despite direct-acting oral anticoagulants effectively reducing stroke risk ( 3 ), atrial fibrillation was still associated with a 1.95-fold increased risk of all-cause mortality ( 4 ). Therefore, risk stratification of survival outcomes in atrial fibrillation patients is an urgent demand for better clinical management.…”

Section: Introductionmentioning

confidence: 99%

Impact of preexisting diabetes mellitus on cardiovascular and all-cause mortality in patients with atrial fibrillation: A meta-analysis

Sun²,

Gong³

et al. 2022

Front. Endocrinol.

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ObjectiveTo determine the impact of preexisting diabetes mellitus on cardiovascular and all-cause mortality in patients with atrial fibrillation (AF) by conducting a meta-analysis.MethodsPubMed and Embase databases were comprehensively searched for relevant studies publishing until May 19, 2022. Cohort studies or post-hoc analyses of clinical trials that investigated the association of diabetes mellitus with cardiovascular or all-cause mortality in AF patients were included.ResultsA total of 21 studies with 526,136 AF patients were identified. The pooled prevalence of diabetes mellitus in patients with AF was 26%. The summary multivariable-adjusted risk ratio (RR) of all-cause mortality was 1.37 (95% confidence intervals [CIs] 1.23–1.53) for patients with diabetes versus those without diabetes. Moreover, diabetes mellitus was also associated with an increased risk of cardiovascular mortality (RR 1.46; 95% CI 1.34–1.58). Stratified analyses suggested that the impact of diabetes on all-cause and cardiovascular mortality was consistently observed in each named subgroup.ConclusionThe presence of diabetes mellitus in patients with AF is associated with an increased risk of cardiovascular and all-cause mortality, even after adjustment for important confounding factors.

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“…DM is considered to be a burden in the clinical course of AF. There is a well-established link between DM or poorly regulated blood glucose levels and increased mortality in patients with AF [ 6 , 21 , 24 , 63 , 77 ]. In particular, a positive linear correlation exists between HbA1c and mortality rates.…”

Section: Relevance Of Glycated Hemoglobin Measurement In Afmentioning

confidence: 99%

“…Although the epidemiology and implications of the AF and DM comorbidity seem to be well described in the current literature [ 6 , 7 ], the precise underlying pathogenic mechanisms still remain an issue of debate [ 8 ]. Significant questions also remain regarding the effect of glycemic control on the development and clinical course of AF.…”

Section: Introductionmentioning

confidence: 99%

Glycemic control and atrial fibrillation: an intricate relationship, yet under investigation

Papazoglou

Κάρτας

Moysidis

et al. 2022

Cardiovasc Diabetol

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Atrial fibrillation (AF) and diabetes mellitus (DM) constitute two major closely inter-related chronic cardiovascular disorders whose concurrent prevalence rates are steadily increasing. Although, the pathogenic mechanisms behind the AF and DM comorbidity are still vague, it is now clear that DM precipitates AF occurrence. DM also affects the clinical course of established AF; it is associated with significant increase in the incidence of stroke, AF recurrence, and cardiovascular mortality. The impact of DM on AF management and prognosis has been adequately investigated. However, evidence on the relative impact of glycemic control using glycated hemoglobin levels is scarce. This review assesses up-to-date literature on the association between DM and AF. It also highlights the usefulness of glycated hemoglobin measurement for the prediction of AF and AF-related adverse events. Additionally, this review evaluates current anti-hyperglycemic treatment in the context of AF, and discusses AF-related decision-making in comorbid DM. Finally, it quotes significant remaining questions and sets some future strategies with the potential to effectively deal with this prevalent comorbidity.

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Does the presence of diabetes mellitus confer an increased risk of stroke in patients with atrial fibrillation on direct oral anticoagulants? A systematic review and meta-analysis

Abstract: Does the presence of diabetes mellitus confer an increased risk of stroke in patients with atrial fibrillation on direct oral anticoagulants? A systematic review and meta-analysis

Cited by 7 publications

References 46 publications

Diabetes and stroke: An important complication

Diabetes and stroke: An important complication

Impact of preexisting diabetes mellitus on cardiovascular and all-cause mortality in patients with atrial fibrillation: A meta-analysis

Glycemic control and atrial fibrillation: an intricate relationship, yet under investigation

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