scholarly journals Dronedarone vs placebo in patients with atrial fibrillation or atrial flutter across a range of renal function: a post hoc analysis of the ATHENA trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Vamos ◽  
J Oldgren ◽  
G.-B Nam ◽  
G Lip ◽  
H Calkins ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Funding Source ◽  
Efficacy And Safety ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background The use of antiarrhythmic drugs in patients with chronic kidney disease (CKD) is challenging due to issues with renal clearance, drug accumulation and increased proarrhythmic risks. Since CKD is a common comorbidity with atrial fibrillation (AF), it is important to establish the efficacy and safety for antiarrhythmic drug treatment in patients with CKD. Purpose To evaluate the efficacy and safety of dronedarone in patients with AF or atrial flutter (AFL) across different stages of renal impairment. Methods In this post-hoc analysis of ATHENA (NCT00174785), a randomised, double-blind trial of dronedarone 400 mg BID vs placebo in patients with AF or AFL plus additional risk factors for death and a calculated glomerular filtration rate ≥10 mL/min, the primary outcome was time to first cardiovascular (CV) hospitalisation or death. Renal function (estimated glomerular filtration rate [eGFR]) was assessed using CKD Epidemiology Collaboration equation and patients were grouped by eGFR (10–44, 45–59, ≥60 mL/min). Log-rank testing and Cox regression were used to compare time to events between treatment groups. Results In ATHENA, 43.6% of placebo and 42.2% of dronedarone patients had mild-to-moderate CKD (Table). Median time to CV hospitalisation/death was longer in all strata for dronedarone vs placebo, reaching significance in the 45–59 and ≥60 mL/min groups (Figure 1). There was a trend towards more treatment-emergent adverse events (TEAEs), deaths and discontinuations due to TEAEs in patients with eGFR 10–44 mL/min. No clear difference in safety was seen between treatment arms except for discontinuations, which were higher with dronedarone. Conclusions This analysis confirms the efficacy of dronedarone, demonstrated in ATHENA, across different stages of renal impairment. Further assessment of safety will require larger populations of patients with CKD. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi

scholarly journals Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis

Haematologica ◽  
2021 ◽  
Author(s):  
Marcelo Capra ◽  
Thomas Martin ◽  
Philippe Moreau ◽  
Ross Baker ◽  
Ludek Pour ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Glomerular Filtration ◽  
Subgroup Analysis ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Phase 3 ◽  
New Therapies

Renal impairment (RI) is common in patients with multiple myeloma (MM) and new therapies that can improve renal function are needed. The Phase 3 IKEMA study (NCT03275285) investigated isatuximab (Isa) with carfilzomib and dexamethasone (Kd) vs Kd in relapsed MM. This subgroup analysis examined results from patients with RI, defined as estimated glomerular filtration rate

scholarly journals A Novel Creatinine-Based Equation to Estimate Glomerular Filtration Rate in Chinese Population With Chronic Kidney Disease: Implications for DOACs Dosing in Atrial Fibrillation Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Ling-Yun Zhou ◽  
Wen-Jun Yin ◽  
Jun Zhao ◽  
Bi-Kui Zhang ◽  
Can Hu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Linear Regression Analysis ◽  
Dynamic Imaging ◽  
Adverse Outcomes

Background: Over/under-estimating renal function may increase inappropriate dosing strategy associated adverse outcomes; however, previously reported equations to estimate renal function have limited accuracy in chronic kidney disease (CKD) patients. Consequently, we intended to develop a novel equation to precisely estimate renal function and subsequently guide clinical treatment for CKD patients.Methods: A novel approach, Xiangya-s equation, to estimate renal function for CKD patients was derived by linear regression analysis and validated in 1885 patients with measured glomerular filtration rate (mGFR) < 60 ml/min/1.73 m2 by renal dynamic imaging at three representative hospitals in China, with the performance evaluated by accuracy, bias and precision. In the meanwhile, 2,165 atrial fibrillation (AF) patients who initiated direct oral anticoagulants (DOACs) between December 2015 and December 2018 were identified and renal function was assessed by estimated creatinine clearance (eCrCl). Events per 100 patient-years was calculated. Cox proportional hazards regression was applied to compare the incidence of outcomes of each group.Results: Xiangya-s equation demonstrated higher accuracy, lower bias and improved precision when compared with 12 creatinine-based and 2 CysC-based reported equations to estimate GFR in multi-ethnic Chinese CKD patients. When we applied Xiangya-s equation to patients with AF and CKD prescribed DOACs, wide variability was discovered in eCrCl calculated by the Cockcroft-Gault (CG), Modification of Diet in Renal Disease Study (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Xiangya equation which we had developed for generally patients and Xiangya-s equations, which persisted after grouping by different renal function stages. Equation choice affected drug-dosing adjustments, with the formulas agreeing for only 1.19%, 5.52%, 33.22%, 26.32%, and 36.61% of potentially impacted patients for eCrCl cutoffs of <15, <30, 15–49, 30–49, ≥50 ml/min, respectively. Relative to CG equation, accordance in DOACs dosage was 81.08%, 88.54%, 62.25%, and 47.68% for MDRD, CKD-EPI, Xiangya and Xiangya-s equations for patients with CrCl < 50 ml/min (eCrCl cutoffs of <30, 30–49, ≥50 ml/min), respectively. Reclassification of renal function stages by Xiangya-s equation was significantly associated with stroke or systemic embolism, non-major clinically relevant bleeding and any bleeding events.Conclusion: Xiangya-s equation provides more accurate GFR estimates in Chinese CKD patients who need consecutive monitoring of renal function, which may assist clinicians in choosing appropriate drug dosages.

scholarly journals Effect of once‐weekly exenatide on estimated glomerular filtration rate slope depends on baseline renal risk: A post hoc analysis of the EXSCEL trial

2020 ◽  
Vol 22 (12) ◽  
pp. 2493-2498
Author(s):  
Annemarie B. van der Aart‐van der Beek ◽  
Lindsay E. Clegg ◽  
Robert C. Penland ◽  
David W. Boulton ◽  
C. David Sjöström ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Post Hoc Analysis ◽  
Post Hoc

scholarly journals Efficacy and safety of dronedarone vs placebo in patients with atrial fibrillation or atrial flutter across a spectrum of renal function: post hoc analyses of the EURIDIS-ADONIS trials

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Thind ◽  
W Zareba ◽  
D Atar ◽  
H Crijns ◽  
J Zhu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Adverse Events ◽  
Atrial Flutter ◽  
Cox Regression ◽  
Wide Spectrum ◽  
Funding Source ◽  
Efficacy And Safety ◽  
Private Company ◽  
Post Hoc

Abstract Background/Introduction The use of antiarrhythmic drugs in patients with chronic kidney disease (CKD) is complex because impaired renal clearance can cause increased drug levels, and risk of intolerance or adverse events. Since CKD commonly co-occurs with atrial fibrillation/atrial flutter (AF/AFL), it is important to establish efficacy and safety for such drugs when used in AF/AFL patients with CKD. Purpose To evaluate the efficacy and safety of dronedarone in patients with AF or AFL across different levels of renal function. Methods This post hoc analysis evaluated pooled data from two multicentre, double-blind, randomised (2:1) trials of rhythm control with dronedarone 400 mg twice daily vs placebo. Primary endpoint was time to first recurrence of AF or AFL. Renal function (estimated glomerular filtration rate [eGFR]) was assessed with the CKD-Epidemiology Collaboration equation. Patients were grouped by eGFR strata. Log-rank testing and Cox regression were used to compare time to events between treatment groups. Results Most (85%) patients had mild or mild-to-moderate decrease in eGFR (Table 1). Median time to first AF recurrence was significantly longer in the dronedarone vs placebo group for all eGFR subgroups except the 30–44 mL/min group (Figure 1), where the trend was consistent; however, the small population size may have precluded meaningful analyses in this subgroup. Serious adverse events, deaths, and treatment discontinuations did not differ notably between each group irrespective of eGFR strata. Conclusions This analysis confirms the efficacy and safety of dronedarone in patients with AF across a wide spectrum of renal function. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi

scholarly journals Different glomerular filtration rate estimating formula for prescribing DOACs in oldest patients: appropriate dosage and bleeding risk. Post hoc analysis of a prospective cohort

2021 ◽  
Author(s):  
Valeria Calsolaro ◽  
Chukwuma Okoye ◽  
Sara Rogani ◽  
Alessia Maria Calabrese ◽  
Umberto Dell’Agnello ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Cystatin C ◽  
Prospective Cohort ◽  
Filtration Rate ◽  
Statistical Significance ◽  
Bleeding Risk ◽  
Post Hoc Analysis ◽  
Ckd Stage ◽  
Post Hoc

Abstract Background Direct oral anticoagulants (DOACs) pharmacokinetics depends on estimated glomerular filtration rate (eGFR), whose estimation is crucial for optimal risk/benefit balance. Aims To assess the concordance among different eGFR formulas and the potential impact on DOACs prescription appropriateness and bleeding risk in oldest hospitalized patients. Methods Post hoc analysis of a single-centre prospective cohort study. eGFR was calculated by creatinine-based (MDRD, CKD-EPICr, BIS1) and creatinine–cystatin-C-based (CKD-EPIComb and BIS2) formulas. Patients were stratified according to eGFR [severely depressed (SD) 15–29; moderately depressed (MD) 30–49; preserved/mildly depressed (PMD): ≥ 50 ml/min/1.73 m2]. Concordance between the different equations was assessed by Cohen’s kappa coefficient. Results Among AF patients, 841 (59.2% women, mean age 85.9 ± 6.5 years) received DOACs. By CKD-EPICr equation, 135 patients were allocated in the SD, 255 in the MD and 451 in the PMD group. The concordance was excellent only between BIS 2 and CKD-EPIComb and MDRD and CKD-EPICr, while was worse (from good to poor) between the other formulas. Indeed, by adding cystatin-C almost over 1/3 of the patients were reallocated to a worse eGFR class. Bleeding prevalence increased by 2–3% in patients with discordant eGFR between formulas, reallocated to a worse chronic kidney disease (CKD) stage, although without reaching statistical significance. CKD-EPIComb resulted the best predictor of bleeding events (AUROC 0.71, p = 0.03). Discussion This study highlights the variability in CKD staging according to different eGFR formulas, potentially determining inappropriate DOACs dosing. Although the cystatin-C derived CKDEPIComb equation is the most accurate for stratifying patients, BIS1 may represent a reliable alternative.

MO459RENAL FUNCTION AMONG PATIENTS WITH NEW DIAGNOSIS OF ATRIAL FIBRILLATION - RESULTS FROM THE NATIONWIDE FINACAF- STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Heini Jyrkilä ◽  
Kati Kaartinen ◽  
Leena Martola ◽  
Olli Halminen ◽  
Jari Haukka ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Study Cohort ◽  
Number Of Patients ◽  
Increased Risk ◽  
Combining Data ◽  
The Mean

Abstract Background and Aims Chronic kidney disease (CKD) is a global public health problem with increasing number of patients due to obesity, hypertension, diabetes, and aging. CKD is an independent risk factor for atrial fibrillation (AF) and the incidence of AF in patients with CKD is two- to threefold higher compared to the general population. Relationship between CKD and AF is bidirectional, and the incidence of impaired renal function is higher in patients with AF. Both AF and CKD are associated with increased risk of stroke and systemic thromboembolism, and also bleeding. The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study among AF patients conducted as a retrospective register-based linkage study combining data from several Finnish health care registers. We aimed to characterize demographics and comorbities of AF patients included in FinACAF according to stages of renal function. Method FinACAF- study collects data from 411 000 patients covering all Finnish AF patients from 1 January 2004 to 31 December 2018. Using national unique personal identification number, individual patients’ data from ten nationwide population registries and six regional laboratory databases (∼282 000, 77% of the patients) are linked together. Inclusion criteria of this substudy were all patients who had new ICD-10 AF diagnosis (code I48) between January 2010 and December 2018 and measured estimated glomerular filtration rate (eGFR) within the proximity of AF the diagnosis. Results Of the whole study cohort, 128 538 were included in this substudy. The mean age at the time of AF diagnosis was 73 years (range 18 to 107 years) and 48.9 % of the patients were female. The age of AF patients increased (Figure 1) and eGFR decreased (Figure 2) in various stages of glomerular filtration at the cohort entry during 2010-2018 are shown in Figures 1 and 2. Prevalence of various comorbidities and the mean age at the baseline are shown in the Table. Most of the comorbidities were more common in patients with lower eGFR levels. Conclusion During 2010-2018 the mean age of new AF patients increased in Finland, and simultaneously the renal function decreased. Also, patients with impaired glomerular filtration rate had more often comorbidities increasing the risk of thromboembolism and bleeding. The findings emphasize appropriate control of these risks in AF patients, especially with reduced renal function.

scholarly journals Efficacy and safety of dapagliflozin according to baseline blood pressure – observations from DECLARE-TIMI 58 Trlial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Furtado ◽  
I Raz ◽  
E.L Goodrich ◽  
M.S Sabatine ◽  
S.D Wiviott
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Severe Hypertension ◽  
Incidence Rates ◽  
Funding Source ◽  
Efficacy And Safety ◽  
Volume Depletion ◽  
Artery Disease

Abstract Background Type 2 diabetes mellitus (T2DM) is associated with heightened risk of cardio-renal complications. In DECLARE-TIMI 58, dapagliflozin, compared to placebo, reduced hospitalization for heart failure (HHF) and renal events (the composite of sustained decrease in glomerular filtration rate of at least 40%, progression to end-stage renal disease or death due to renal causes) in a broad range of patients with T2DM, without increase in volume depletion or amputations (two adverse events potentially related to blood pressure lowering). It is uncertain whether the cardio-renal effects of dapagliflozin are partially mediated by an anti-hypertensive effect and whether patients with normal blood pressure can be safely treated with this drug class. In this pre-specified analysis, we report the interaction of those results with baseline systolic blood pressure (SBP). Purpose To analyze efficacy and safety of dapagliflozin stratified according to baseline SBP. Methods DECLARE-TIMI 58 enrolled 17,160 patients with T2DM with either prior atherosclerotic disease or risk factors. Following the most recent guidelines, patients were categorized according to the following baseline SBP levels: <120, 120–129, 130–139, 140–159 and ≥160 mmHg (respectively, optimal, normal, high normal, grade 1 hypertension and grade 2–3 or severe hypertension). Additionally, spline models were developed to explore the association between SBP and the incidence rates of HHF and renal events. Models were adjusted for: diastolic blood pressure, prior coronary artery disease, prior stroke, peripheral artery disease, dyslipidemia, history of hypertension, prior HF, glomerular filtration rate <60 ml/min/1.73 m2, urinary albumin to creatinin ratio >300 mg/g, age, race, body mass index, DM duration and region. Results From the overall trial population, 2557, 3686, 4385, 5501 and 1031 patients were categorized as optimal, normal, high normal, grade 1 hypertension and grade 2–3 or severe hypertension, respectively. After adjustment for clinical co-variates, there was an independent association between SBP and HHF or renal events in the placebo arm, with a “U”-shaped association for both events. Moreover, patients with severe hypertension were at the highest risk for HHF and renal events (Figure 1, Panels A and B). While the HHF benefit of dapagliflozin was amplified in patients with severe hypertension (p-int=0.041), the benefit of dapagliflozin did not differ by SBP category for renal events (p-int=0.15), (Figure 1, Panels C and D). There was no increase in symptoms of volume depletion or amputation at any level of SBP (p-int = 0.93 and 0.28, respectively). Conclusion In patients with T2DM, baseline SBP was independently associated with HHF and renal events with a “U”-shaped relationship. Patients with severe hypertension experienced a greater benefit with dapagliflozin for HHF, and renal events were consistently reduced with dapagliflozin across all levels of SBP. Figure 1. HHF and renal events according to SBP Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): AstraZeneca

P391Estimated glomerular filtration rate levels and risk of stroke in individuals with diabetes mellitus and atrial fibrillation

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
R Westreich ◽  
O Barrett ◽  
L Kezerle ◽  
M Leventer Roberts ◽  
M Avgil Tsadok ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Mortality Risk ◽  
Impaired Renal Function ◽  
Filtration Rate ◽  
Historical Cohort ◽  
Increased Risk

Abstract Funding Acknowledgements pfizer Background Diabetes mellitus (DM) is associated with increased risk of embolic complications in non-valvular atrial fibrillation (NVAF). Chronic kidney disease (CKD) has been shown in some studies to increase the risk of stroke. This finding is not consistent among all studies. Therefore the relationship between kidney function, diabetes and stroke risk is complex and warrants further investigation. Purpose To assess the incidence rates and risk of ischemic stroke and mortality by baseline Estimated Glomerular Filtration Rate (eGFR) levels among individuals with AF and DM. Methods A prospective, historical cohort study using our electronic medical records database. The study population included all members 21 years old, with a first diagnosis of NVAF between January 1, 2010 to December 31, 2016 and a minimal follow-up period of 1 year. Among those patients identified as diabetics, we compared three groups of patients according to eGFR levels at the time of AF diagnosis: eGFR ≥ 60, between 30-60 and ≤ 30 or chronic dialysis or kidney transplant. Results A total of  17,567 cases were included in the final analysis, of them, 11013 (62.7%) had eGFR ≥ 60, 4930 (28%) with eGFR between 30-60 and 1624 (9.24%) with eGFR ≤30 . The median age was 75 years (IQR 65-83) with a majority of females in all groups, 52.5%, 51.2% and 55.5% respectively. The incidence of stroke per 100 person-years in the three study groups was: 1.88 in patients with eGFR ≥ 60, 2.69 in patients with eGFR between 30-60 and 3.34 in those with eGFR ≤ 30 . Impaired renal function was associated with increased risk of stroke in univariate analysis, but not found in the adjusted model  (Adjusted Hazard Ratio (AHR) = 1.04 {95% 0.89-1.23} for eGFR 30-60  and 1.16 {95% CI 0.88-1.51} for eGFR ≤ 30 compared to GFR ≥ 60). incidence of mortality per 100 person-years was 10.78 in patients with  eGFR ≥ 60, 21.49 in patients with eGFR 30-60 and 41.55 in those with eGFR ≤ 30. In both univariate and multivariate analyses, decreased levels of eGFR were associated with increased mortality risk compared to subjects with normal renal function (AHR 1.22 {95%CI 1.14-1.27} and AHR 2.09 {95%CI 1.95-2.24} for eGFR between 30-60 and for eGFR ≤ 30, respectively). Conclusion In this observational prospective cohort of patients with newly diagnosed NVAF, impaired renal function was not found to be associated with increased risk of stroke. Lower eGFR levels were associated with an increased mortality risk.

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