Stroke and Bleeding in Atrial Fibrillation with Chronic Kidney Disease

Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
New England Journal of Medicine (Impact Factor: 55.87). 08/2012; 367(7):625-35. DOI: 10.1056/NEJMoa1105594
Source: PubMed


Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions.
Using Danish national registries, we identified all patients discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. The risk of stroke or systemic thromboembolism and bleeding associated with non-end-stage chronic kidney disease and with end-stage chronic kidney disease (i.e., disease requiring renal-replacement therapy) was estimated with the use of time-dependent Cox regression analyses. In addition, the effects of treatment with warfarin, aspirin, or both in patients with chronic kidney disease were compared with the effects in patients with no renal disease.
Of 132,372 patients included in the analysis, 3587 (2.7%) had non-end-stage chronic kidney disease and 901 (0.7%) required renal-replacement therapy at the time of inclusion. As compared with patients who did not have renal disease, patients with non-end-stage chronic kidney disease had an increased risk of stroke or systemic thromboembolism (hazard ratio, 1.49; 95% confidence interval [CI], 1.38 to 1.59; P<0.001), as did those requiring renal-replacement therapy (hazard ratio, 1.83; 95% CI, 1.57 to 2.14; P<0.001); this risk was significantly decreased for both groups of patients with warfarin but not with aspirin. The risk of bleeding was also increased among patients who had non-end-stage chronic kidney disease or required renal-replacement therapy and was further increased with warfarin, aspirin, or both.
Chronic kidney disease was associated with an increased risk of stroke or systemic thromboembolism and bleeding among patients with atrial fibrillation. Warfarin treatment was associated with a decreased risk of stroke or systemic thromboembolism among patients with chronic kidney disease, whereas warfarin and aspirin were associated with an increased risk of bleeding. (Funded by the Lundbeck Foundation.).

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    • "Data regarding effectiveness in decreasing the risk of stroke in patients with AF receiving haemodialysis are also inconclusive. In one of the latest of such studies, Olesen et al. [52], in a group of more than 900 patients in whom warfarin was used in fewer than 20% of cases, observed for a period of 11 years and found a statistically significant decrease in the risk of the occurrence of stroke or another systemic thromboembolic event. However, in several other studies, such an effect was not observed; what is more, the effect of using OACs was decidedly negative. "
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    ABSTRACT: Oral anticoagulant (OAC) therapy in haemodialysis patients causes a great deal of controversy. This is because a number of pro- and anticoagulant factors play an important role in end-stage renal failure due to the nature of the disease itself. In these conditions, the pharmacokinetic and pharmacodynamic properties of the OACs used change as well. In the case of the treatment of venous thromboembolism, the only remaining option is OAC treatment according to regimens used for the general population. Prevention of HD vascular access thrombosis with the use of OACs is not very effective and can be dangerous. However, OAC treatment in patients with atrial fibrillation in dialysis population may be associated with an increase in the incidence of stroke and mortality. Doubts should be dispelled by prospective, randomised studies; at the moment, there is no justification for routine use of OACs in the above-mentioned indications. In selected cases of OAC therapy in this group of patients, it is absolutely necessary to control and monitor the applied treatment thoroughly. Indications for the use of OACs in patients with end-stage renal disease, including haemodialysis patients, should be currently limited.
    The Scientific World Journal 11/2013; 2013(2):170576. DOI:10.1155/2013/170576 · 1.73 Impact Factor
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    • "Warfarin is indicated in the general population for the treatment of venous thromboembolism (VTE) and for prophylaxis of stroke in patients with atrial fibrillation. A recent non-randomized retrospective database analysis confirmed that in patients with non-valvular atrial fibrillation and chronic kidney disease, the use of warfarin or aspirin reduced stroke but increased risk of bleeding [1]. However, in patients on dialysis, warfarin is widely used for nonvalvular atrial fibrillation, though the ratio of risks to benefits remains unclear [2-6]. "
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    ABSTRACT: Warfarin prescribing patterns for hemodialysis patients with atrial fibrillation vary widely amongst nephrologists. This may be due to a paucity of guiding evidence, but also due to concerns of increased risks of warfarin use in this population. The literature lacks clarity on the balance of warfarin therapy between prevention of thrombotic strokes and the increased risks of bleeding in hemodialysis patients with atrial fibrillation. We performed a survey of Canadian Nephrologists, assessing warfarin prescribing practice, and measured the certainty in making these choices. Respondents were consistently uncertain about warfarin use for atrial fibrillation. This uncertainty increased with a history of falls or starting hemodialysis, even when a high CHADS2 or CHA2DS2VASc score was present. The majority of respondents agreed that clinical equipoise existed about the use of oral anticoagulation in hemodialysis patients with atrial fibrillation (72.2%) and that the results of a randomized controlled trial would be relevant to their practice (98.2%). A randomized controlled trial of warfarin use in hemodialysis patients with atrial fibrillation would clarify the risks and benefits of warfarin use in this population.
    BMC Nephrology 08/2013; 14(1):174. DOI:10.1186/1471-2369-14-174 · 1.69 Impact Factor
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    • "✘ No neuroimaging results available • Stroke risk increased as eGFR fell (P = .0082 for trend) Friberg et al, 2012 34 ; retrospective cohort 182,678 patients with AF • Patients with renal failure (ie, stage 1 CKD or worse) had a multivariable HR 1.11 (CI 0.99-1.25) of ischemic stroke 8113 with renal failure • Multivariable HR 1.16 (CI 1.05-1.28) of any stroke/TIA/systemic embolism Olesen et al, 2012 37 "
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    ABSTRACT: Chronic kidney disease (CKD) has a very well-established link with cardiovascular disease. Below stage 3 CKD (glomerular filtration rate <60 mL/min), there is a progressive increase in both total mortality and cardiovascular-specific mortality as kidney function declines; indeed, it is more likely for a patient with CKD stage 3 to die of cardiovascular disease than to progress to CKD stage 4 and beyond. Arrhythmia is particularly common in patients with CKD. Depending on the study and measurement used, the prevalence of patients with CKD with chronic atrial fibrillation (AF) is quoted at 7% to 18%, rising to 12% to 25% for those older than 70 years. These rates are up to 2 to 3 times higher than in the general population. Of all patients with AF, 10% to 15% will have CKD. However, not all standard rate and rhythm methods are suitable for this population and those that are tend to be less effective. Meanwhile, anticoagulation has long been a thorny subject, with much conflicting evidence around the balance between bleeding and stroke risk. To help clarify this, we first highlight the challenges of performing evidence-based medicine in the patient with renal disease, and then review recent and emerging research to suggest an approach to the management of patients with renal disease who have AF. We also review the potential role of the different new oral anticoagulant drugs in CKD.
    American heart journal 08/2013; 166(2):230-9. DOI:10.1016/j.ahj.2013.05.010 · 4.46 Impact Factor
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