Thromboembolic and Bleeding Risk in Atrial Fibrillation Patients with Chronic Kidney Disease: Role of Anticoagulation Therapy.
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SUBMITTER: Magnocavallo M
PROVIDER: S-EPMC7796391 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Thromboembolic and Bleeding Risk in Atrial Fibrillation Patients with Chronic Kidney Disease: Role of Anticoagulation Therapy.
Magnocavallo Michele M Bellasi Antonio A Mariani Marco Valerio MV Fusaro Maria M Ravera Maura M Paoletti Ernesto E Di Iorio Biagio B Barbera Vincenzo V Della Rocca Domenico Giovanni DG Palumbo Roberto R Severino Paolo P Lavalle Carlo C Di Lullo Luca L
Journal of clinical medicine 20201228 1
Atrial fibrillation (AF) and chronic kidney disease (CKD) are strictly related; several independent risk factors of AF are often frequent in CKD patients. AF prevalence is very common among these patients, ranging between 15% and 20% in advanced stages of CKD. Moreover, the results of several studies showed that AF patients with end stage renal disease (ESRD) have a higher mortality rate than patients with preserved renal function due to an increased incidence of stroke and an unpredicted elevat ...[more]
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Project description:Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting up to six million people in the United States and more than 35 million individuals worldwide. Thromboembolism, including stroke, represents the most common AF-related morbidity and mortality and data indicate that anticoagulation can mitigate this risk by 65%. Our understanding of thromboembolism in AF, however, remains incomplete, and the mechanisms by which AF increases thromboembolic risk are areas of ongoing investigation and debate. Current guidelines do not differentiate between the frequency and duration of AF episodes (AF burden) when selecting which patients with AF should be treated with anticoagulation for thromboembolic risk reduction. Recent data, primarily using cardiac implantable electronic devices (CIEDs) such as pacemakers, implantable cardioverter-defibrillators, and implantable loop recorders, however, have challenged this longstanding notion that AF burden does not influence thromboembolic risk. Continuous and automated cardiac rhythm monitoring via CIEDs with accurate and rapid acquisition and transmission of rhythm data also affords the opportunity to study the relationship between AF burden and thromboembolism and novel ways to reduce thromboembolic risk while minimizing the risk associated with chronic anticoagulation use. This manuscript will review the associations between subclinical, CIED-detected atrial arrhythmias and thromboembolic events. It will also discuss the emergence of "tailored anticoagulation," an anticoagulation strategy wherein CIEDs and remote AF monitoring are employed to allow dynamic administration of oral anticoagulation only around episodes of AF, and the holding of anticoagulation during prolonged periods of sinus rhythm when the thromboembolic risk associated with AF is presumably very low.
| S-EPMC7252665 | biostudies-literature
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.
| S-EPMC5974258 | biostudies-literature
Project description:Coexisting cancer in patients with atrial fibrillation (AF) has been associated with thromboembolism and bleeding. We used Danish population-based medical databases to conduct a population-based cohort study that included all AF patients who redeemed a prescription for vitamin K antagonists (VKA) or non-VKA oral anticoagulant (NOAC) between July 2004 and December 2013. We characterized these patients according to the presence (N = 11,855) or absence (N = 56,264) of a cancer diagnosis before redemption of their oral anticoagulant prescription, and then examined their 1-year risk of thromboembolic or bleeding complications or death. We next used Cox regression to compare the hazard ratios for complications among VKA- or NOAC-treated AF patients with versus without a cancer diagnosis, after adjusting for sex, age, and CHA2 DS2 VASc score. One-year risks of thromboembolic complications in AF patients who redeemed a VKA prescription were similar in those with (6.5%) and without (5.8%) cancer [hazard ratio (HR) 1.0 (95% confidence interval (CI): 0.93, 1.1)]. This also was found for bleeding complications (5.4% vs. 4.3%, HR 1.1 [95% CI: 1.0, 1.2]). For AF patients with cancer who redeemed a NOAC prescription, risks were also similar for thromboembolic complications (4.9% of cancer patients vs. 5.1% of noncancer patients, HR 0.80 [95% CI: 0.61, 1.1]), and for bleeding complications (4.4% vs. 3.1%, HR 1.2 [95% CI: 0.92, 1.7]). The absolute risks of thromboembolic or bleeding complications were nearly the same in patients with and without cancer who redeemed prescription for VKAs or NOACs.
| S-EPMC5463075 | biostudies-literature
Project description:PurposeAdvanced chronic kidney disease (CKD), including end-stage renal disease (ESRD) on dialysis, increases thromboembolic risk among patients with atrial fibrillation (AF). This study examined the comparative safety and efficacy of direct-acting oral anticoagulant (DOAC) compared to warfarin or no oral anticoagulant (OAC) in AF patients with advanced CKD or ESRD on dialysis.Materials and methodsUsing data from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, 260 non-valvular AF patients with advanced CKD (defined as estimated glomerular filtration rate <30 mL/min per 1.73/m²) or ESRD on dialysis were enrolled from June 2016 to July 2020. The study population was categorized into DOAC, warfarin, and no OAC groups; and differences in major or clinically relevant non-major (CRNM) bleeding, stroke/systemic embolism (SE), myocardial infarction/critical limb ischemia (CLI), and death were assessed.ResultsDuring a median 24 months of follow-up, major or CRNM bleeding risk was significantly reduced in the DOAC group compared to the warfarin group [hazard ratio (HR) 0.11, 95% confidence interval (CI) 0.01 to 0.93, p=0.043]. In addition, the risk of composite adverse clinical outcomes (major or CRNM bleeding, stroke/SE, myocardial infarction/CLI, and death) was significantly reduced in the DOAC group compared to the no OAC group (HR 0.16, 95% CI 0.03 to 0.91, p=0.039).ConclusionAmong AF patients with advanced CKD or ESRD on dialysis, DOAC was associated with a lower risk of major or CRNM bleeding compared to warfarin and a lower risk of composite adverse clinical outcomes compared to no OAC. ClinicalTrials.gov (NCT02786095).
| S-EPMC9826956 | biostudies-literature
Project description:BackgroundThe role of anticoagulation therapy for stroke prevention in older atrial fibrillation (AF) patients with chronic kidney disease (CKD) remains unclear. Therefore, we conducted a meta-analysis to explore the efficacy and safety of anticoagulation therapy in this population.MethodsThe Cochrane Library, PubMed, and Embase databases were systematically searched for studies reporting the effect of anticoagulation therapy in older patients with AF and CKD. The risk ratios (RRs) and 95% confidence intervals (CIs) were regarded as the risk estimates. A random-effects model selected was to evaluate the treatment outcomes. The presentations were based on the Preferred Reporting Items for reporting systematic reviews and meta-analyses statement.ResultsA total of 7 studies with 24,794 older patients with AF and CKD were included. The follow-up of the included studies ranged from 0.9 to 9.0 years. In older patients with no dialysis, compared with nonanticoagulants, anticoagulants reduced the risk of all-cause death (RR 0.66, 95% CI 0.54-0.79), but had comparable risks of ischemic stroke/transient ischemic attack (TIA, RR 0.91, 95% CI 0.46-1.79) and bleeding (RR 1.17, 95% CI 0.86-1.60). In older patients with dialysis, compared with nonanticoagulants, anticoagulants increased the risk of bleeding (RR 1.37, 95% CI 1.09-1.74), but had similar risks of ischemic stroke/TIA (RR 1.18, 95% CI 0.88-1.58) and death (RR 0.87, 95% CI 0.60-1.27).ConclusionCompared with nonanticoagulation, anticoagulation therapy is associated with a reduced risk of death in older AF patients with nondialysis, but an increased risk of bleeding in older patients with dialysis.
| S-EPMC6824694 | biostudies-literature
Project description:Management of atrial fibrillation (AF) is a clinical conundrum in people with kidney failure. Stroke risk is disproportionately high, but clinicians have a limited armamentarium to improve outcomes in this population in whom there is a concurrently high bleeding risk. Direct oral anticoagulants may have a superior benefit-risk profile compared with vitamin K antagonists in people on hemodialysis. Although research has predominantly focused on identifying a safe and effective oral anticoagulation option to reduce stroke risk in people with kidney failure (and predominantly those on hemodialysis), it remains uncertain how clinicians discriminate between people who would derive net clinical benefit as opposed to net harm. The recommended CHA2DS2-VASc score cutoffs provide poor discriminatory value, and there is an urgent need to identify robust markers of thromboembolic risk in kidney failure. There is increasing data to challenge the prior dogma of risk equivalence across AF type, and the American Heart Association highlights moving beyond AF as a binary entity to consider the prognostic significance of AF burden. Implantable cardiac monitor studies reveal high rates and varied burden of subclinical and paroxysmal AF in people on hemodialysis. The association between AF burden and the proarrhythmic environment of hemodialysis with cyclical volume loading, offloading, and electrolyte changes is not well studied. We review the significance of AF burden as a contributor to thromboembolic risk, its potential as the missing link in risk assessment, and updated evidence for anticoagulation in people with kidney failure.
| S-EPMC10403723 | biostudies-literature
Project description:ObjectiveTo evaluate performance of the ABC (Age, Biomarkers, Clinical history)-bleeding risk score in estimating major bleeding risk in Chinese patients with atrial fibrillation (AF) on oral anticoagulation (OAC) therapy in real-world practice.MethodsData were collected from the Chinese Atrial Fibrillation Registry study (CAFR). Patients were stratified into low-, medium-, and high-risk groups based on ABC-bleeding risk score with 1-year major bleeding risk (<1%, 1-2%, and > 2%) and modified HAS-BLED score (≤1, 2, and > 2 points). Cox proportional-hazards (Cox-PH) models were used to determine the association of major bleeding incidence with bleeding scores. Harrell's C-index of the two scores were compared. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) at 1 year were employed to evaluate the reclassification capacity. The calibration curve was plotted to compare the predicted major bleeding risk using ABC-bleeding risk score with the observed annualized event rate. The decision analysis curves (DCA) were performed to show the clinical utilization of two scores in identifying major bleeding events.ResultsThe study included 2,892 AF patients on OAC therapy. After the follow-up of 3.0 years, 48 patients had major bleeding events; the incidence of a bleeding event in the low-, medium-, and high-risk groups according to ABC-bleeding risk score was 0.31% (reference group, HR = 1.00),0.51% (HR = 1.83, 95%CI: 0.91-3.69, P = 0.09), and 1.49% (HR = 4.92, 95%CI: 2.34-10.30, P < 0.001), respectively. Major bleeding incidence had an independent association with growth differentiation factor 15 (GDF-15) level (HR = 2.16, 95%CI: 1.27-3.68, P = 0.005) after adjusting components of the HAS-BLED score and cTnT-hs level. The ABC-bleeding score showed a Harrell's C-index of 0.67 (95%CI: 0.60-0.75) in estimating major bleeding risk, which was non-significant compared to the modified HAS-BLED score (0.67 vs. 0.63; P = 0.38). NRI and IDI also revealed comparable reclassification capacity of ABC-bleeding risk score compared with HAS-BLED score (14.6%, 95%CI: -10.2%, 39.4%, P = 0.25; 0.2%, 95%CI -0.1 to 0.9%, P = 0.64). Cross-tabulation of the two scores showed that the ABC-bleeding score outperformed the HAS-BLED score in identifying patients with a high risk of major bleeding. The calibration curve showed that the ABC-bleeding risk score overestimated the observed major bleeding risk. DCA did not show any difference in net benefit when using either of the scores.ConclusionThis study verified the value of the ABC-bleeding risk score in assessing major bleeding risk in Chinese patients with AF on OAC therapy in real-world practice. Despite the overestimation of major bleeding risk, ABC-bleeding score performed better in stratifying patients with a high risk than the modified HAS-BLED score. Combining the two scores could be a clinically practical strategy for precisely stratifying AF patients, especially those at a high risk of major bleeding, and further supporting the optimization of OAC treatment.
| S-EPMC9669712 | biostudies-literature
Project description:BackgroundThe predictive value of bleeding risk scores for atrial fibrillation in older patients is not as well known. The goal of this study was to evaluate the predictive value of HASBLED, ORBIT and ATRIA for major bleeding (MB) and intracranial hemorrhage (ICH) in patients ≥ 75 years with atrial fibrillation and oral anticoagulation (OAC).MethodsA retrospective unicenter study including patients ≥ 75 years with atrial fibrillation (AF) and OAC. A total of 7613 patients ≥ 75 years with AF and OAC included between 2014 and 2018 (registry: NCT04364516). We analyzed the discriminative value of HASBLED, ATRIA and ORBIT scores for bleeding endpoints (major bleeding as primary endpoint and intracerebral hemorrhage as secondary). Cox regression was used to predict major bleeding with each scale and also for searching other variables potentially predictor of major bleeding. Model discrimination was assessed using Harrell's C-statistic. Calibration was assessed with goodness-of-fit test proposed by Gronnesby and Borgan.ResultsDuring a mean follow up of 4.0 years (IQR: 2.4-5.7 years), 729 patients developed MB (2.61 per 100 patients/year) and 243 patients developed ICH (0.85 per 100 patients/year). Three scores showed a low discrimination for major bleeding, being ORBIT the best (HASBLED C statistic = 0.557; ATRIA C statistic = 0.568; ORBIT C statistic = 0.595) and also a low discrimination for ICH (HASBLED C statistic = 0.509; ATRIA C statistic = 0.522; ORBIT C statistic = 0.526). Among the variables that are part of the scores and other baseline characteristics, after multivariable adjustment only sex (male), dementia, prior admission for bleeding, anemia and liver disease were found as a predictors of MB.ConclusionsIn older patients under oral anticoagulation with atrial fibrillation, the risk scores HASBLED, ATRIA and ORBIT showed a weak discrimination for major bleeding and intracranial hemorrhage. Therefore, other better alternatives should be evaluated for this purpose.
| S-EPMC10568544 | biostudies-literature
Project description:ObjectivesWe identified factors associated with thromboembolic and bleeding events in two contemporary cohorts of anticoagulated patients with atrial fibrillation (AF), treated with either vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs).DesignProspective, multicentre observational study.Setting461 centres in seven European countries.Participants5310 patients receiving a VKA (PREvention oF thromboembolic events - European Registry in Atrial Fibrillation (PREFER in AF), derivation cohort) and 3156 patients receiving a NOAC (PREFER in AF Prolongation, validation cohort) for stroke prevention in AF.Outcome measuresRisk factors for thromboembolic events (ischaemic stroke, systemic embolism) and major bleeding (gastrointestinal bleeding, intracerebral haemorrhage and other life-threatening bleeding).ResultsThe mean age of patients enrolled in the PREFER in AF registry was 72±10 years, 40% were female and the mean CHA2DS2-VASc Score was 3.5±1.7. The incidence of thromboembolic and major bleeding events was 2.34% (95% CI 1.93% to 2.74%) and 2.84% (95% CI 2.41% to 3.33%) after 1-year of follow-up, respectively.Abnormal liver function, prior stroke or transient ischaemic attack, labile international normalised ratio (INR), concomitant therapy with antiplatelet or non-steroidal anti-inflammatory drugs, heart failure and older age (≥75 years) were independently associated with both thromboembolic and major bleeding events.With the exception of unstable INR values, these risk factors were validated in patients treated with NOACs (PREFER in AF Prolongation Study, 72±9 years, 40% female, CHA2DS2-VASc 3.3±1.6). For each single point decrease on a modifiable bleeding risk scale we observed a 30% lower risk for major bleeding events (OR 0.70, 95% CI 0.64 to 0.76, p<0.01) and a 28% lower rate of thromboembolic events (OR 0.72, 95% CI 0.66 to 0.82, p<0.01).ConclusionAttending to modifiable risk factors is an important treatment target in anticoagulated AF patients to reduce thromboembolic and bleeding events. Initiation of anticoagulation in those at risk of stroke should not be prevented by elevated bleeding risk scores.
| S-EPMC6475354 | biostudies-literature
Project description:Patients with CKD represent a vulnerable population where the risks of atrial fibrillation, ischemic stroke, and bleeding are all heightened. Although large randomized, controlled trials in the general population clearly demonstrate that the benefits of warfarin and direct-acting oral anticoagulants outweigh the risks of bleeding, no such studies have been conducted in patients when their creatinine clearance falls below 25-30 ml/min. Without randomized, controlled trial data, the role of anticoagulation in patients with CKD with atrial fibrillation remains unclear and our practice is informed by a growing body of imperfect literature such as observational and pharmacokinetic studies. This article aims to present a contemporary literature review of the benefits versus harms of anticoagulation in atrial fibrillation for patients with CKD stages 3, 4, 5, and 5 on dialysis. Although unanswered questions and areas of clinical equipoise remain, this piece serves to assist physicians in interpreting the complex body of literature and applying it to their clinical care.
| S-EPMC6364544 | biostudies-literature