Differential effect of anticoagulation therapy in patients older versus younger than 80 years with atrial fibrillation and severe chronic kidney disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Fortuny Frau ◽  
S Raposeiras-Roubin ◽  
J.M Andreu-Cayuelas ◽  
A Garcia-Egido ◽  
C Ortiz-Cortes ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cox Regression ◽  
Anticoagulation Therapy ◽  
Funding Source ◽  
Bleeding Events ◽  
Younger Patients ◽  
Cox Regression Analysis ◽  
Glomerular Filtrate

Abstract Introduction In non-valvular atrial fibrillation (NVAF) patients, advanced age and chronic kidney disease (CKD) raise the thrombotic and bleeding rates, making the decision of antithrombotic therapy a challenge. Therefore, we conducted an analysis to explore the efficacy and safety of anticoagulation therapy in this population (AF patients ≥80 years) in comparison with younger AF patients (<80 years). Methods For these results we have analyzed data from FIBRA, a multicentric Spanish retrospective registry on patients with CKD-EPI <30 ml/min/1.73 m2 and newly diagnosed NVAF. For death, multivariable Cox regression analysis was developed. For embolic and bleeding events, competing-risks regression based on Fine and Gray's proportional subhazards model was performed, being death the competing event Results We analyzed 405 patients with CKD-EPI <30 ml/min/1.73 m2. 232 were ≥80 years-old (57.3%). Median of CHA2DS2-VASC and HASBLED scores were 5 and 3 in patients ≥80 years, respectively, and 3 and 2 in patients <80 years, respectively. The prescription of antithrombotic therapies in elderly versus younger patients is shown in Figure 1. During a follow-up of 4.6±2.5 years, 205 died (50.6%), 34 had embolic events (8.4%) and 85 had bleeding outcomes (21.0%). After multivariate analysis, no benefit of anticoagulation therapy was found for mortality in both, older and younger patients. In patients ≥80, anticoagulation was associated with higher rates of bleeding events without a decrease in embolic outcomes. Conclusion In our registry, anticoagulation has not shown benefit in NVAF patients ≥80 years with glomerular filtrate rate <30 ml/min/1.73 m2, increasing the risk of bleeding events without reducing embolic outcomes. Figure 1 Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): BMS-Pfizer alliance unconditional grant

scholarly journals Impact of antithrombotic therapy in the prognosis of atrial fibrillation patients with advanced chronic kidney disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.M Andreu Cayuelas ◽  
S Raposeiras-Roubin ◽  
E Fortuny Frau ◽  
A Garcia Del Egido ◽  
J Seller-Moya ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Antithrombotic Therapy ◽  
Anticoagulation Therapy ◽  
Bleeding Event ◽  
Funding Source ◽  
Newly Diagnosed ◽  
Bleeding Events ◽  
Cox Regression Analysis

Abstract Introduction Chronic kidney disease (CKD) is associated with an elevated thromboembolic and bleeding risk in atrial fibrillation (AF) patients, so the decision of antithrombotic therapy is a challenge. Purpose To analyze mortality, embolic and bleeding events in patients with advanced CKD and AF. Methods Multicentric retrospective registry on patients with AF and advanced CKD (CKD-EPI <30 mL/min/1.73 m2). For death, multivariable Cox regression analysis was developed. For embolic and bleeding events, competing-risks regression based on Fine and Gray's proportional subhazards model was performed, being death the competing event Results We analysed 405 patients with advanced CKD and newly diagnosed AF. 57 patients were not treated with antithrombotic therapy (14.1%), 80 only with antiplatelet/s (19.8%), 211 only with anticoagulation (52.1%), and 57 with anticoagulant plus antiplatelet/s (14.1%). During a follow-up of 4.6±2.5 years, 205 died (50.6%), 34 had embolic events (8.4%) and 85 had bleeding outcomes (21.0%). Bleeding event rate was significantly lower in patients without antithrombotic therapy (Figure). After multivariate analysis, anticoagulant treatment was associated with higher bleeding rates, without differences in mortality or embolic events (Table). Conclusion Anticoagulation therapy was associated with a significant increase in bleeding events in patients with advanced CKD and newly diagnosed AF. None of the antithrombotic therapy regimens resulted in lower embolic events rate neither benefit in mortality. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): This study was supported by an unconditional grant from BMS-Pfizer

Risk factors for major bleeding during prolonged anticoagulation therapy in cancer-associated venous thromboembolisms: from the COMMAND VTE registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Nishimoto ◽  
Y Yamashita ◽  
K Kim ◽  
T Morimoto ◽  
S Saga ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Major Bleeding ◽  
Gastrointestinal Cancer ◽  
Cox Regression ◽  
Anticoagulation Therapy ◽  
Terminal Cancer ◽  
Funding Source

Abstract Background/Introduction Patients with cancer-associated venous thromboembolisms (VTEs) are at a high risk for recurrent VTEs and are recommended to receive prolonged anticoagulation therapy if they are at a low risk for bleeding. However, there are no established risk factors for bleeding during prolonged anticoagulation therapy. Purpose We aimed to identify the risk factors for major bleeding during prolonged anticoagulation therapy in cancer-associated VTE patients. Methods The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3027 consecutive patients with acute symptomatic VTEs among 29 Japanese centers between January 2010 and August 2014. After excluding those without active cancer (N=2332), patients with major bleeding (N=15), death (N=17), and lost to follow-up (N=10) within 10 days after the diagnosis, and those without anticoagulation therapy beyond 10 days after the diagnosis (N=61), the present study population consisted of 592 cancer-associated VTE patients with anticoagulation therapy beyond 10 days after the diagnosis. The outcome measurement was International Society of Thrombosis and Hemostasis (ISTH) major bleeding during anticoagulation therapy beyond 10 days, which occurred before the first discontinuation of the anticoagulation therapy. We constructed a multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of the potential risk factors for major bleeding. As a sensitivity analysis, we used Fine and Gray's method to estimate the HR and 95% CI, taking into account the competing risk of all-cause death. Results During a median follow-up period of 199 days, major bleeding occurred in 72 patients (31 patients within 3 months; 41 beyond 3 months). The cumulative incidence of major bleeding was 5.8% at 3-months, 13.8% at 1-year, 17.5% at 2-year, and 28.1% at 5-years. The most frequent major bleeding site was gastrointestinal (47%), followed by intracranial (17%) and genitourinary (11%). Major bleeding tended to occur from the sites of the cancer, however, the sites of the cancer and sites of major bleeding were not necessarily concordant. The multivariable Cox regression model demonstrated that terminal cancer (adjusted HR, 4.17; 95% CI, 2.22–7.85, P<0.001), chronic kidney disease (adjusted HR, 1.89; 95% CI 1.06–3.37, P=0.031), and gastrointestinal cancer (adjusted HR, 1.78; 95% CI, 1.04–3.04, P=0.037) were independently associated with an increased risk of major bleeding. After taking into account the competing risk of all-cause death, the multivariable Cox regression model demonstrated almost consistent results with the main analysis. Conclusions Major bleeding events were common during prolonged anticoagulation therapy in real-world cancer-associated VTE patients. Terminal cancer, chronic kidney disease, and gastrointestinal cancer were the independent risk factors for major bleeding. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Bypass Grafting vs Endovascular Therapy in Patients With Non-Dialysis-Dependent Chronic Kidney Disease and Chronic Limb-Threatening Ischemia (CRITISCH Registry)

2020 ◽  
Vol 27 (4) ◽  
pp. 599-607
Author(s):  
Konstantinos Stavroulakis ◽  
Asimakis Gkremoutis ◽  
Matthias Borowski ◽  
Giovanni Torsello ◽  
Dittmar Böckler ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Chronic Kidney Disease ◽  
Overall Survival ◽  
Kidney Disease ◽  
Endovascular Therapy ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Bypass Grafting ◽  
Cox Regression Analysis

Purpose: To report the outcomes of bypass grafting (BG) vs endovascular therapy (EVT) in patients with non-dialysis-dependent chronic kidney disease (CKD) and chronic limb-threatening ischemia (CLTI). Materials and Methods: The CRITISCH Registry is a prospective, national, interdisciplinary, multicenter registry evaluating the current practice of all available treatment options in 1200 consecutive CLTI patients. For the purposes of this analysis, only the 337 patients with non-dialysis-dependent CKD treated by either BG (n=86; median 78 years, 48 men) or EVT (n=251; median age 80 years, 135 men) were analyzed. The primary composite outcome was amputation-free survival (AFS); secondary outcomes were overall survival (OS) and amputation-free time (AFT). All outcomes were evaluated in Cox proportional hazards models; the results are reported as the hazard ratio (HR) and 95% confidence interval (CI). Results: The Cox regression analysis revealed a significantly greater hazard of amputation or death after BG (HR 1.78, 95% CI 1.05 to 3.03, p=0.028). The models for AFT and overall survival also suggested a higher hazard for BG, but the differences were not significant (AFT: HR 1.66, 95% CI 0.78 to 3.53, p=0.188; OS: HR 1.41, 95% CI 0.80 to 2.47, p=0.348). The absence of runoff vessels (HR 1.73, 95% CI 1.15 to 2.60, p=0.008) was associated with a decreased AFS. The likelihood of amputation was higher in male patients (HR 2.21, 95% CI 1.10 to 4.45, p=0.027) and was associated with a lack of runoff vessels (HR 1.95, 95% CI 0.96 to 3.95, p=0.065) and myocardial infarction (HR 3.74, 95% CI 1.23 to 11.35, p=0.020). Death was more likely in patients without runoff vessels (HR 1.76, 95% CI 1.11 to 2.80, p=0.016) and those with a higher risk score (HR 1.73, 95% CI 1.03 to 2.91, p=0.038). Conclusion: This analysis suggested that BG was associated with poorer AFS than EVT in patients with non-dialysis-dependent CKD and CLTI. Male sex, previous myocardial infarction, and the absence of runoff vessels were additionally identified as predictors of poorer outcomes.

6116Thromboembolic risk in infection-related atrial fibrillation: is infection or atrial fibrillation the sinner?

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Gundlund ◽  
J B Olesen ◽  
J H Butt ◽  
M A Christensen ◽  
G H Gislason ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Hospital Admission ◽  
Cox Regression ◽  
Anticoagulation Therapy ◽  
First Year ◽  
Thromboembolic Events ◽  
Cox Regression Analysis ◽  
Hazard Ratios ◽  
Study Population ◽  
Hospital Contact

Abstract Introduction Infection-related atrial fibrillation (AF) has been associated with similar risk of thromboembolic events as AF without a concurrent infection. However, it is unknown whether the increased thromboembolic risk in this patient group is primarily associated with AF or with the infection. Purpose We compared type of infection and 1-year outcomes in patients with AF during an infection and in patients with infection without AF. Methods By crosslinking data from Danish nationwide registries, AF naïve patients admitted with an infection from 1996–2016 were identified. Patients with infection-related AF (defined as patients who developed AF during their hospital admission with infection) were matched 1:3 on age, calendar year, sex, and type of infection (gastrointestinal infection, pneumonia, urinary tract infection, sepsis, and other infections) with those who had infection without AF. Cumulative incidences of thromboembolic events were calculated using the Aalen Johansen estimator and adjusted hazard ratios (HR) of thromboembolic events and hospital contacts with AF were assessed by multivariable Cox regression analysis comparing those with infection-related AF with those with infection without AF. Results The study population comprised 30,711 patients with infection-related AF and 92,133 patients with infection without AF (median age 79 years [interquartile range 71–86] and 47.6% males in both groups). In general, patients with infection-related AF had more concurrent diseases than patients with infection without AF. During the first week after the hospital admission, 9.8% of the patients with infection-related AF and 0.1% of the patients with infection without AF initiated oral anticoagulation therapy. During the first year after the infection, 7.6% of patients with infection-related AF and 4.4% of patients with infection without AF had a thromboembolic event, while 36.1% and 1.8% had a new hospital-contact with AF. Cumulative incidences of thromboembolic events are depicted in the Figure. In the multivariable models, infection-related AF was associated with an increased 1-year risk of thromboembolic events and new hospital contacts with AF compared with infection without AF (HR 2.05, 95% confidence interval (CI) 1.94–2.17 for thromboembolic events and HR 26.06, 95% CI 24.72–27.48 for new AF episodes, respectively). Conclusion More than one third of patients with infection-related AF had a new hospital contact with AF during the first year after their infection. Further, infection-related AF was associated with a significantly increased 1-year risk of thromboembolic events compared with infection without AF. Consequently, this study suggests that AF begets AF, even if it presents during an infection. Acknowledgement/Funding None

scholarly journals P0603INFLUENCE OF FERRITIN VALUES IN THE PORGNOSIS OF ACUTE KIDNEY INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Pablo Díez ◽  
Andres Fernández Ramos ◽  
Patricia Muñoz Ramos ◽  
Marta Sanz Sainz ◽  
Begoña Santos Sánchez-Rey ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Iron Metabolism ◽  
Cox Regression ◽  
Transferrin Saturation ◽  
Kidney Injury ◽  
Iron Storage ◽  
Reason For Admission

Abstract Background and Aims Acute Kidney Injury (AKI) is one of the most frequent causes of hospitalization and many factors have been associated to its prognosis and recovery. The role of iron in AKI physiopathology and its influence is not well known. Recent studies have shown that elevated levels of catalytic iron are associated with higher mortality in patients with AKI, however, catalytic iron is not available in usual clinical practice. Ferritin, especially abundant in the liver, is the primary intracellular iron storage protein. A small amount is secreted to the circulation and is an indirect marker of total body iron deposits. In this study we analyze the influence of iron, with ferritin values, in the prognosis of AKI. Method We developed a retrospective, single-center study that enrolled patients with AKI, hospitalized in our center between 2013 and 2014 with iron metabolism values in the first 72 hours after admission. At baseline, we collected demographic information, comorbidities, reason for admission and iron metabolism values (ferritin, transferrin, transferrin saturation index and serum iron). We analyzed variables associated with low and high ferritin values and its impact in AKI long-term prognosis using univariate and multivariable Cox regression. Results Of the 1731 analyzed patients, 833 (48.1%) had ferritin records. The mean age was 78±14 years and 48% of the patients were women. The most frequent comorbidity was hypertension (76%), followed by chronic kidney disease (46%), dyslipidemia (44%), heart failure (31%), diabetes mellitus (29%) and atrial fibrillation (27%). The most frequent reason for admission was infection (35%) followed by AKI (19%). Ferritin values differed significantly according age (p<0.0001), sex (p=0.024), diabetes (0.012), hypertension (p=0.002), neoplasia (p=0.016), reason for admission (p=0.018), baseline CKD-EPI (0.012) and lactate at admission (p<0.0001). During the hospitalization, 165 (20%) patients died. Factor associated to mortality were ferritin>500 ng/ml (p=0.013), lactate at admission (p<0.001), age (p=0.045), hypertension (p=0.014), dyslipidemia (p<0.001), ischemic heart disease (p=0.006), chronic kidney disease (p=0.001), baseline CKD-EPI (p=0.01), atrial fibrillation (p=0.005), neoplasia (p=0.023), Barthel index (p<0.001) and hemoglobin (p=0.006) and bicarbonate (p=0.012) at admission. Multivariate logistic regression demonstrated that ferritin levels over 500 ng/mL was an independent predictor of mortality (1.6 [1,1-2,3] HR [CI 95%]) (p=0.013). Conclusion Ferritin values higher than 500 ng/mL independently predicts mortality in patients admitted with AKI.

scholarly journals Safety of dabigatran in patients with atrial fibrillation and chronic kidney disease: pharmacokinetic and pharmacogenetic aspects

2020 ◽  
pp. 65-73
Author(s):  
A. I. Skripka ◽  
P. O. Bochkov ◽  
K. A. Akmalova ◽  
R. V. Shevchenko ◽  
P. M. Krupenin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Nucleotide Polymorphisms ◽  
Bleeding Events ◽  
Day Range ◽  
High Interindividual Variability ◽  
Trough Concentrations ◽  
Moderate Chronic Kidney Disease ◽  
D Values

Background: despite well-studied safety profile of dabigatran its interactions with genetic polymorphism parameters are poorly understood, especially in patients with moderate chronic kidney disease (CKD). This study was aimed to evaluate relationships between CES1 and ABCB1 polymorphism, dabigatran trough plasma concentration (DTPC) and bleeding events in patients with AF and CKD.Methods: patients with atrial fibrillation (AF) and stage 3 CKD treated with dabigatran 110mg or 150 mg have been included in the study. Real-time PCR was used to evaluate single nucleotide polymorphisms (SNPs) of the ABCB1 gene (rs1045642, rs4148738) and CES1 gene (rs2244613). A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index.Results: a total of 60 patients, aged 51–89 years (median age 76 years) were evaluated. Compared with patients given 150 mg twice a day, those given 110 mg twice a day were older (79 vs 67.5, p < 0.0001) and had lower creatinine clearance (CrCl) (50.5 vs 60.5 mL/min/1.73 m2, p = 0.015). We found C/D values to have high interindividual variability (mean 365.9 ± 290.4 μg/ml: mg/day, range 23.64-1452.73). Individuals with CKD 3B had higher concentration of dabigatran compared with those with 3A stage (488.7 ± 232.3 vs 332 ± 297.8 μg/ml : mg/day, p = 0.02). Consequently, there also was negative correlation of C/D with CrCl (r = -0.4, p = 0.0015). Evaluated SNPs (rs1045642, rs4148738, and rs2244613) did not affect C/D values (H test p > 0.05).Conclusions: C/D values were significantly higher in patients with CKD 3B stage and those treated with dabigatran 110 mg. There was no influence of aforementioned SNPs on dabigatran trough concentrations and clinical outcomes.

scholarly journals MO159CHA2DS2-VASC SCORE AS A PREDICTOR OF CARDIOVASCULAR MORTALITY IN CHRONIC KIDNEY DISEASE PATIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Nina Vodošek Hojs ◽  
Robert Ekart ◽  
Sebastjan Bevc ◽  
Nejc Piko ◽  
Radovan Hojs
Keyword(s):  
Chronic Kidney Disease ◽  
Regression Analysis ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Cardiovascular Mortality ◽  
Cox Regression ◽  
High Sensitivity ◽  
Cardiovascular Death ◽  
Cox Regression Analysis

Abstract Background and Aims Cardiovascular mortality is high in chronic kidney disease (CKD) patients. Recognizing patients with higher cardiovascular risk might help in their treatment. CHA2DS2-VASc score was originally used to predict cerebral infarction in patients with atrial fibrillation (AF). However, it is also useful in predicting outcome in different cardiovascular conditions, independent of the presence of AF. Therefore, the aim of our research was to assess the role of CHA2DS2-VASc score in cardiovascular mortality in CKD patients. Method Eighty-seven non-dialysis CKD patients from our outpatient clinic were included. At the time of inclusion, medical history data and standard blood results were collected and CHA2DS2-VASc score was calculated. Patients were followed for assigned time or until their death. Mean follow-up time was 1696.45±564.60 days. Results Descriptive statistics of our patients are presented in table 1. During follow-up 11 patients suffered from cardiovascular death. Univariate Cox regression analysis showed that CHA2DS2-VASc score is a significant predictor of cardiovascular mortality (HR: 2.19, CI: 1.42-3.37, p=0.001). In multivariate Cox regression analysis in which CHA2DS2-VASc score, serum creatinine, urinary albumin/creatinine, haemoglobin, high sensitivity CRP and intact PTH were included, CHA2DS2-VASc score was an independent predictor of cardiovascular mortality (HR: 2.04, CI: 1.20-3.45, p=0.008) (table 2). Conclusion CHA2DS2-VASc score is a simple and quick way to identify cardiovascular risk in CKD patients.

scholarly journals Primary hemostatic disorders drive early and late major bleedings of patients with atrial fibrillation after transcatheter aortic valve replacement

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K Matsushita ◽  
B Marchandot ◽  
S Hess ◽  
M Kibler ◽  
C Sato ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cox Regression ◽  
Academic Research ◽  
Surrogate Marker ◽  
Bleeding Complications ◽  
Rank Test ◽  
Bleeding Events ◽  
Major Life ◽  
Cox Regression Analysis ◽  
The Impact

Abstract Introduction Patients with atrial fibrillation (AF) are likely to have multiple co-morbidities and receive anticoagulants after TAVR, which lead to a poor prognosis including bleeding events. Closure time adenosine diphosphate (CT-ADP) is a primary hemostasis point-of-care test used as a surrogate marker of high molecular weight (HMW) multimers defect of Von Willebrand factor (VWF). Our prior studies suggest that prolongation of CT-ADP (&gt;180 seconds) after TAVR is a major determinant of early and late major/life-threatening bleeding complications (MLBCs). Purpose To evaluate the impact of post-procedural CT-ADP &gt;180sec on bleeding events in AF patients. Methods We included 878 patients from our prospective TAVR registry between 2010 and 2019. Bleeding complications were assessed according to the VARC-2 (Valve Academic Research Consortium-2) criteria. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year after TAVR. Ongoing primary haemostasis disorder was defined by post-procedure CT-ADP &gt;180sec. Primary endpoint was the occurrence of MLBCs during the first year and the second endpoint was 1-year MACCE. Results Patients with AF had a higher incidence of all-cause mortality (15% vs. 8%, p=0.002), MACCE (29% vs. 20%, p=0.002), and MLBCs (20% vs. 12%, p=0.001) within 1-year compared to non-AF patients. When the cohort was split into 4 subgroups according to AF and CT-ADP &gt;180sec, patients with AF and CT-ADP &gt;180sec had the highest risk of MLBCs (log-rank test; p&lt;0.001) (Figure). Multivariate Cox regression analysis confirmed that the patients with AF and CT-ADP &gt;180sec had 4.6-fold higher risk of MLBCs within 1 year compared to non-AF patients with CT-ADP ≤180sec (hazard ratio: 4.60; 95% confidence interval: 2.18 - 9.68; p&lt;0.001). Conclusion Among TAVR patients, AF with post-procedural CT-ADP &gt;180 sec was identified as a strong independent predictor of MLBCs at 1-year follow-up. Our study suggest that persistent primary haemostasis disorders contribute to a higher risk of bleeding events particularly in AF patients and may be considered for a tailored and risk-adjusted antithrombotic therapy after TAVR. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Matsushita received a grant from Edwards Lifesciences.

scholarly journals Stroke and Major Bleeding when Switching from Warfarin to Apixaban in Patients with Advanced Chronic Kidney Disease and Prevalent Atrial Fibrillation

2021 ◽  
Author(s):  
Katherine Garlo ◽  
Thomas Mavrakanas ◽  
Wei Wang ◽  
Elisabeth Burdick ◽  
David Charytan
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Major Bleeding ◽  
The United States ◽  
Bleeding Events ◽  
Part D ◽  
Stage 4 ◽  
Ischemic Attack

Abstract Background Apixaban is the most widely used direct oral anticoagulant in patients with chronic kidney disease (CKD). Data on the incidence of stroke and major bleeding after switching from warfarin to apixaban in patients with prevalent atrial fibrillation (AF) and CKD are limited.Methods Warfarin users with stage 4-5 CKD not on dialysis and non-valvular AF prior to Jan 1,2012 were identified from the United States Data Renal System CKD dataset and individuals switching to apixaban from Jan 1,2012 -Dec 31, 2015 were identified. The incidence of stroke (ischemic or hemorrhagic), transient ischemic attack, or systemic thromboembolism and major bleeding events were estimated. Outcomes were compared between individuals switching to apixaban and those continuing warfarin using survival analyses with inverse probability treatment weighting. Individuals were censored at the time of anticoagulation discontinuation, loss of Medicare part D coverage, dialysis, kidney transplant, a 2nd switch in anticoagulant class, or death. Results 1762 individuals with advanced CKD and AF were initially on warfarin; 71 (4.0%) switched to apixaban (57.8% male, mean age 78.2 years (SD ±6.6), 78.9% white, mean CHA2DS2-VASc 5.0 (SD ±1.5), mean HAS-BLED 2.2 (SD ±0.5) and 1691 (96.0%) continued warfarin (47.6% male, mean age 80.1 years (SD ±8.7), 87.9% white, mean CHA2DS2-VASc 5.5 (SD ±1.6), mean HAS-BLED 2.5 (SD ±0.8). The incidence of stroke in the apixaban switch and warfarin continuation groups were 0.02/patient-year (95%CI 0.002-0.12) and 0.06/patient-year (95%CI 0.05-0.07) (p=0.21). Incidence of major bleeding were 0.02/patient-year (95% CI 0.002-0.13) and 0.06 (95% CI 0.03-0.04) (p =0.44) in the switch and warfarin groups, respectively. In adjusted models, the risk of stroke (HR 0.27 (95% CI 0.04-1.99)) and major bleeding (HR 0.41 (95% CI 0.06-3.02)) trended lower in the apixaban switch compared to the warfarin continuation group.Conclusions The incidence and risk of stroke and major bleeding trended lower in individuals with stage 4-5 CKD and prevalent AF who switched from warfarin to apixaban than individuals continuing warfarin. Our findings support a strategy of switching prevalent AF patients with late stage CKD from warfarin to apixaban. Additional studies including a larger number of events with a longer-duration of follow-up are needed to refine effect estimates.

scholarly journals Association of rs11780592 Polymorphism in the Human Soluble Epoxide Hydrolase Gene (EPHX2) with Oxidized LDL and Mortality in Patients with Diabetic Chronic Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Stefanos Roumeliotis ◽  
Athanasios Roumeliotis ◽  
Aikaterini Stamou ◽  
Stylianos Panagoutsos ◽  
Vangelis G. Manolopoulos ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Epoxide Hydrolase ◽  
Cox Regression ◽  
Oxidized Ldl ◽  
Intima Media Thickness ◽  
Soluble Epoxide Hydrolase ◽  
Cox Regression Analysis ◽  
Functional Polymorphisms ◽  
All Cause Mortality

Soluble epoxide hydrolase 2 (EPHX2) is an enzyme promoting increased cellular apoptosis through induction of oxidative stress (OS) and inflammation. The EPHX2 gene which encodes soluble EPHX2 might be implicated in the pathogenesis and development of OS and atherosclerosis. We aimed to assess the possible association between two functional polymorphisms of the EPHX2 gene (rs2741335 and rs11780592) with oxidized LDL (ox-LDL), carotid atherosclerosis, mortality, and cardiovascular (CV) disease in 118 patients with diabetic chronic kidney disease (CKD). At baseline, ox-LDL and carotid intima-media thickness (cIMT) were evaluated and all patients were followed for seven years with outcomes all-cause mortality and CV events. rs11780592 EPHX2 polymorphism was associated with ox-LDL, cIMT, albuminuria, and hypertension. Compared to AG and GG, AA homozygotes had higher values of albuminuria, ox-LDL, and cIMT ( p = 0.046 , p = 0.003 , and p = 0.038 , respectively). These associations remained significant, even after grouping for the G allele. After the follow-up period, 42/118 patients died (30/60 with AA genotype, 11/42 with AG genotype, and 1/12 with GG genotype) and 49/118 experienced a new CV event (fatal or nonfatal). The Kaplan-Meier analysis revealed that patients with the AA genotype exhibited a significantly higher mortality risk, compared to patients with AG and GG genotypes ( p = 0.006 ). This association became even stronger, when AG and GG genotypes were grouped (AA vs. AG/GG, p = 0.002 ). AA homozygotes were strongly associated with all-cause mortality in both univariate (hazard ratio HR = 2.74 , confidence interval CI = 1.40 – 5.35 , p = 0.003 ) and multivariate Cox regression analysis ( HR = 2.61 , CI = 1.32 – 5.17 , p = 0.006 ). In conclusion, our study demonstrated that genetic variations of EPHX2 gene were associated with increased circulating ox-LDL, increased cIMT, and all-cause mortality in diabetic CKD. Since EPHX2 regulates the cholesterol efflux and the oxidation of LDL in foam cells and macrophages, our study suggests that a genetic basis to endothelial dysfunction and OS might be present in diabetic CKD.

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