Project description:AimsThe optimal anticoagulation regimen in patients with end-stage kidney disease (ESKD) undergoing atrial fibrillation (AF) catheter ablation is unknown. We sought to describe the real-world practice of peri-procedural anticoagulation management in patients with ESKD undergoing AF ablation.Methods and resultsPatients with ESKD on haemodialysis undergoing catheter ablation for AF in 12 referral centres in Japan were included. The international normalized ratio (INR) before and 1 and 3 months after ablation was collected. Peri-procedural major haemorrhagic events as defined by the International Society on Thrombosis and Haemostasis, as well as thromboembolic events, were adjudicated. A total of 347 procedures in 307 patients (67 ±9 years, 40% female) were included. Overall, INR values were grossly subtherapeutic [1.58 (interquartile range: 1.20-2.00) before ablation, 1.54 (1.22-2.02) at 1 month, and 1.22 (1.01-1.71) at 3 months]. Thirty-five patients (10%) suffered major complications, the majority of which was major bleeding (19 patients; 5.4%), including 11 cardiac tamponade (3.2%). There were two peri-procedural deaths (0.6%), both related to bleeding events. A pre-procedural INR value of 2.0 or higher was the only independent predictor of major bleeding [odds ratio, 3.3 (1.2-8.7), P = 0.018]. No cerebral or systemic thromboembolism occurred.ConclusionDespite most patients with ESKD undergoing AF ablation showing undertreatment with warfarin, major bleeding events are common while thromboembolic events are rare.
Project description:Patients with end-stage kidney disease (ESKD) have an elevated incidence of atrial fibrillation (AF) and are at increased risk for thromboembolic events. However, these patients are also at increased risk for bleeding and it is unclear whether they benefit from an oral anticoagulant. Point prevalent on July 1, 2015, only ~28% of dialysis patients with AF were on oral anticoagulation. Warfarin was the most commonly used oral anticoagulant, followed by apixaban, while dabigatran and rivaroxaban were rarely used. This article reviews the current evidence regarding each oral anticoagulant especially as they relate to patients with ESKD.
Project description:End-stage renal disease (ESRD) patients have a higher prevalence of diabetes mellitus, hypertension, congestive heart failure and advanced age, along with an increased incidence of non-valvular atrial fibrillation (AF), thereby increasing the risk for cerebrovascular accidents. Systemic anticoagulation is therefore recommended in patients with ESRD with AF to reduce the risk and complications from thromboembolism. Paradoxically, these patients are at an increased risk of bleeding due to great degree of platelet dysfunction and impaired interaction between platelet and endothelium. Currently, CHA2DS2-VASc and Hypertension, Abnormal liver/kidney function, Stroke, Bleeding, Labile INR, Elderly, Drugs or alcohol (HAS-BLED) are the recommended models for stroke risk stratification and bleeding risk assessment in patients with AF. There is conflicting data regarding benefits and risks of medications such as antiplatelet agents, warfarin and direct oral anticoagulants in ESRD patients with AF. Moreover, there is no randomized controlled trial data to guide the clinical decision making. Hence, a multi-disciplinary approach with annual re-evaluation of treatment goals and risk-benefit assessment has been recommended. In this article, we review the current recommendations with risks and benefits of anticoagulation in patients with ESRD with AF.
Project description:BACKGROUND:Cardiological societies recommend, in their guidelines, that patients with atrial fibrillation and an intermediate (or higher) risk of stroke and systemic embolization should be treated with oral anticoagulant drugs. For patients who do not have mitral valve stenosis or a mechanical valve prosthesis, non-vitamin-K dependent oral anticoagulants (NOAC) are preferred over vitamin K antagonists (VKA) for this purpose. It is unclear, however, whether patients with chronic kidney disease and atrial fibrillation benefit from oral anticoagulation to the same extent as those with normal kidney function. It is also unclear which of the two types of anti - coagulant drug is preferable for patients with chronic kidney disease; NOAC are, in part, renally eliminated. METHODS:This review is based on pertinent publications retrieved by a selective literature search, and on international guidelines. RESULTS:Current evidence suggests that patients with atrial fibrillation who have chronic kidney disease with a glomerular filtration rate (GFR) above 15 mL/ min/1.73 m² should be treated with an oral anticoagulant drug if they have an at least intermediate risk of embolization, as assessed with the CHA2DS2-VASc score. For patients with advanced chronic kidney disease (GFR from 15 to 29 mL/ min/1.73 m²), however, this recommendation is based only on registry studies. For dialysis patients with atrial fibrillation, decisions whether to give oral anticoagulant drugs should be taken on an individual basis, in view of the elevated risk of hemorrhage and the unclear efficacy of such drugs in these patients. The subgroup analyses of the NOAC approval studies show that, for patients with atrial fibrillation and chronic kidney disease with a creatinine clearance of >25-30 mL/min, NOAC should be given in preference to VKA, as long as the patient does not have mitral valve stenosis or a mechanical valve prosthesis. For those whose creatinine clearance is less than 25 mL/min, the relative merits of NOAC versus VKA are still debated. CONCLUSION:The cardiological societies' recommendation that patients with atrial fibrillation should be given oral anticoagulant drugs applies to the majority of such patients who also have chronic kidney disease.
Project description:Genetic factors play a key role in the pathogenesis of atrial fibrillation (AF). We would like to establish an association between previously described single-nucleotide polymorphisms (SNPs) and AF in haemodialysed patients with end-stage kidney disease (ESKD-HD) as well as to assess the cumulative effect of all genotyped SNPs on AF risk. Sixteen SNPs were genotyped in 113 patients with AF-ESKD-HD and in 157 controls: without AF (NAF) and with ESKD-HD. The distribution of the risk alleles was compared in both groups and between different sub-phenotypes. The multilocus genetic risk score (GRS) was calculated to estimate the cumulative risk conferred by all SNPs. Several loci showed a trend toward an association with permanent AF (perm-AF): CAV1, Cx40 and PITX2. However, GRS was significantly higher in the AF and perm-AF groups, as compared to NAF. Three of the tested variables were independently associated with AF: male sex, history of myocardial infarction (MI) and GRS. The GRS, which combined 13 previously described SNPs, showed a significant and independent association with AF in a Polish population of patients with ESKD-HD and concomitant AF. Further studies on larger groups of patients are needed to confirm the associations.
Project description:BackgroundConcomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well established to prevent thromboembolism, the applicability in patients under long-term dialysis remains debatable. The study aimed to determine the efficacy and safety of anticoagulation in the dialysis-dependent population.Methods and resultsAn updated network meta-analysis based on MEDLINE, EMBASE, and the Cochrane Library was performed. Studies published up to December 2022 were included. Direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, apixaban 2.5/5 mg twice daily), vitamin K antagonists (VKAs), and no anticoagulation were compared on safety and efficacy outcomes. The outcomes of interest were major bleeding, thromboembolism, and all-cause death. A total of 42 studies, including 3 randomized controlled trials, with 185 864 subjects were pooled. VKAs were associated with a significantly higher risk of major bleeding than either no anticoagulation (hazard ratio [HR], 1.47; 95% CI, 1.34-1.61) or DOACs (DOACs versus VKAs; HR, 0.74 [95% CI, 0.64-0.84]). For the prevention of thromboembolism, the efficacies of VKAs, DOACs, and no anticoagulation were equivalent. Nevertheless, dabigatran and rivaroxaban were associated with fewer embolic events. There were no differences in all-cause death with the administration of VKAs, DOACs, or no anticoagulation.ConclusionsFor dialysis-dependent populations, dabigatran and rivaroxaban were associated with better efficacy, while dabigatran and apixaban demonstrated better safety. No anticoagulation was a noninferior alterative, and VKAs were associated with the worst outcomes.
Project description:BackgroundOnly small randomized trials have investigated the efficacy and safety of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) and end-stage kidney disease.ObjectivesTo perform a systematic review and meta-analysis comparing anticoagulation with DOACs to VKAs in patients with NVAF undergoing chronic hemodialysis.MethodsA systematic search using Medline, Web of Science, and Embase was performed. All randomized trials comparing DOACs with VKAs in patients with NVAF undergoing chronic hemodialysis were included. As primary endpoint, we analyzed all-cause mortality. As secondary endpoints, we investigated total bleeding events, life-threatening or major bleeding events, and thromboembolic events or stroke. We used the odds ratio as outcome measure and fitted a random-effects model due to the expected heterogeneity.ResultsThree studies fulfilled the inclusion criteria comprising 383 patients (218 on apixaban or rivaroxaban, 165 on VKA). No significant difference between DOACs and VKAs regarding death (OR, 0.94; 95% CI, 0.55-1.63; p = .84), total bleedings (OR, 0.99; 95% CI, 0.63-1.54; p = .96) and life-threatening or major bleeding (OR, 0.65; 95% CI, 0.32-1.33, p = .24) was detected. There was a trend toward a reduction of thromboembolic events or stroke in patients receiving DOACs (OR, 0.39; 95% CI, 0.14-1.05; p = .06).ConclusionOrally administered activated factor X inhibitors carried a similar risk of bleeding and death when compared with VKAs in patients with NVAF undergoing chronic hemodialysis. Moreover, there was a trend towards a reduction of thromboembolic events or stroke in patients receiving DOACs.
Project description:BackgroundThe net benefit of oral anticoagulation (OAC) with vitamin K antagonists or direct oral anticoagulants in patients with advanced chronic kidney disease and atrial fibrillation remains uncertain.ObjectivesWe examined the use, efficacy, and safety of OAC in patients with estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m2 (including dialysis-treated patients) and atrial fibrillation.MethodsIn a retrospective cohort study, patients diagnosed with atrial fibrillation and eGFR of <30 mL/min/1.73 m2 were identified in national Danish registers between 2010 and 2022. Initiation of OAC was identified based on redemption of a relevant prescription. One-year risks of thromboembolic event, major bleeding, and death associated with OAC and no treatment were computed and standardized to the distribution of risk factors in the sample based on hazards determined in multiple Cox regression models adjusted for age and sex.ResultsA total of 3208 patients were included (mean age 80 years, 52.8% males, 20.9% chronic dialysis). OAC was initiated in 1375 (42.9%) patients, of whom 48.1% were vitamin K antagonists and 51.9% were direct oral anticoagulants. One-year risks in nontreated and anticoagulated patients were 4.8% (95% CI, 3.8%-5.7%) and 3.6% (95% CI, 2.8%-4.6%; P = .028) for thromboembolic event, 7.6% (95% CI, 6.6%-8.7%) and 10.5% (95% CI, 9.3%-12.1%; P < .001) for major bleeding, and 36.3% (95% CI, 34.2%-38.3%) and 29.6% (95% CI, 27.6%-31.6%; P < .001) for death, respectively.ConclusionIn a retrospective study on patients with advanced chronic kidney disease and atrial fibrillation, OAC was associated with overall decreased 1-year risk of thromboembolic event and death offset by increased 1-year risk of major bleeding.
Project description:Patients with atrial fibrillation (AF) are at increased thromboembolic risk, and they suffer more severe strokes with worse outcomes. Most thromboembolic complications of AF are eminently preventable with oral anticoagulation, and the increasing numbers of AF patients mean antithrombotic therapy is the most crucial management aspect of this common arrhythmia. Despite the proven efficacy of warfarin, a string of limitations have meant that it is underused by physicians and patients alike. This has prompted a search for new anticoagulants that could overcome many of the inconveniences of dose variability and anticoagulant monitoring associated with warfarin, but without sacrificing efficacy in thromboprophylaxis. The arrival of new oral anticoagulants has been complemented by improved risk stratification schemes, which permit clinicians to easily and reliably identify patients requiring anticoagulation and their bleeding risk. These advances in AF treatment will hopefully translate into improved outcomes for patients, especially as our experience with the new agents grows.
Project description:Atrial fibrillation (AF) is a frequent comorbid condition in patients with end-stage renal disease on hemodialysis (HD) with a prevalence of up to 27%. The incidence rate of stroke in AF patients on HD is approximately 5%. The AF-associated risk of stroke is a major clinical challenge because current evidence for anticoagulation in HD patients with AF is based on observational data. Results from these observational studies is largely contradictory because they do not show a clear benefit of vitamin K antagonists over no treatment in terms of stroke prevention, and they show an increased risk of hemorrhage associated with anticoagulation treatment in HD patients. HD patients were not included in randomized trials of the direct oral anticoagulants (DOACs), and therefore there is no evidence to support efficacy and safety of DOACs compared to vitamin K antagonists in HD patients. The pharmacological characteristics of DOACs are of particular interest in the HD setting. The factor Xa inhibitors rivaroxaban, apixaban, and edoxaban are not predominantly eliminated via the kidneys. The thrombin inhibitor dabigatran is 80% eliminated via the kidneys but is dialyzable due to its low protein binding. In this narrative review, we examine the current state of evidence regarding the prevalence of AF in patients on HD, the associated risk of stroke, and the efficacy and safety of anticoagulation for stroke prevention in the HD setting. Further, based on the pharmacokinetic properties of DOACs, we discuss their potential use in patients on HD and ongoing randomized trials.