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      Predictive ability of creatinine clearance versus estimated glomerular filtration rate for outcomes in patients with non-valvular atrial fibrillation: Subanalysis of the J-RHYTHM Registry

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          Abstract

          Background

          Renal impairment is a risk factor for various adverse events, especially for death. In general, creatinine clearance (CrCl) is used for dose-adjustments of many drugs including oral anticoagulants, and estimated glomerular filtration rate (eGFR) is adopted for the diagnosis of chronic kidney disease. Predictive ability of CrCl versus eGFR for outcomes in patients with non-valvular atrial fibrillation (NVAF) remains controversial; therefore, this was compared using data from the J-RHYTHM Registry.

          Methods

          Out of 7406 outpatients with NVAF from 158 institutions, 6004 (age, 69.7 ± 9.9 years; men, 71.2%) having data of CrCl (mL/min, by the Cockcroft-Gault formula), eGFR (mL/min/1.73 m 2, by the equations of the Japanese Society of Nephrology), and body surface area (BSA) were analyzed. C-statistics (area under the receiver-operating characteristic curve) of CrCl and eGFR for events were compared by DeLong's test.

          Results

          Thromboembolism, major hemorrhage, and all-cause death occurred in 107 (1.8%), 117 (1.9%), and 154 (2.6%) patients during the 2-year follow-up period. C-statistics of CrCl for each event were 0.609 (95% confidence interval, 0.559–0.658), 0.599 (0.548–0.657), and 0.746 (0.706–0.786); and those of eGFR were 0.542 (0.487–0.597), 0.573 (0.519–0.626), and 0.677 (0.631–0.723), respectively. C-statistics of CrCl for thromboembolism and all-cause death were significantly higher than those of eGFR (P < 0.001 for both). These results were consistent when BSA-unadjusted eGFR was used instead of eGFR (P = 0.002 for thromboembolism and P < 0.001 for all-cause death).

          Conclusions

          CrCl was superior to eGFR in the prediction of adverse outcomes, i.e., thromboembolism and all-cause death in Japanese patients with NVAF.

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          Most cited references21

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          Prediction of Creatinine Clearance from Serum Creatinine

          A formula has been developed to predict creatinine clearance (C cr ) from serum creatinine (S cr ) in adult males: Ccr = (140 – age) (wt kg)/72 × S cr (mg/100ml) (15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18–92. Values for C cr were predicted by this formula and four other methods and the results compared with the means of two 24-hour C cr’s measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr·s of 0.83; on average, the difference between predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.
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            Stroke and bleeding in atrial fibrillation with chronic kidney disease.

            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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              Warfarin treatment in patients with atrial fibrillation: observing outcomes associated with varying levels of INR control.

              We aimed to determine the level of INR control associated with reduced stroke and mortality. The study used a retrospective cohort design using linked inpatient, haematology and mortality data from Cardiff and the Vale of Glamorgan, UK. Anonymised patients admitted with a diagnosis of non-valvular atrial fibrillation (NVAF) were defined as warfarin or non-warfarin treated by number of repeated International Normalised Ratio (INR) tests. Warfarin treated patients (>5 INR tests) categorised as at moderate or high risk of stroke (CHADS2 score > or = 2) with varying levels of INR control were compared to those who did not receive warfarin treatment using Cox proportional hazards models controlling for age, sex and CHADS2 score. Outcome measures were time to stroke and mortality. 6,108 patients with NVAF were identified. 2,235 (36.6%) of these patients had five or more INR readings and of these 486 (21.7%) had CHADS2 score > or = 2. There was significant improvement in time to stroke event in those patients with INR control of greater than 70% of time in therapeutic range (2.0 to 3.0) compared with the non-warfarin treatment group. Overall survival was significantly improved for all warfarin treated groups with INR control of greater than 40% of time in range. Patients with INR control of above 70% of time in range had a significantly reduced risk of stroke. Patient suitability for warfarin treatment should be continuously assessed based on their ability to maintain a consistently therapeutic INR.
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                Author and article information

                Contributors
                Journal
                Int J Cardiol Heart Vasc
                Int J Cardiol Heart Vasc
                International Journal of Cardiology. Heart & Vasculature
                Elsevier
                2352-9067
                10 June 2020
                August 2020
                10 June 2020
                : 29
                : 100559
                Affiliations
                [a ]Department of Internal Medicine and Cardiology, Nippon Medical School Tama-Nagayama Hospital, Tokyo, Japan
                [b ]Saiseikai Toyama Hospital, Toyama, Japan
                [c ]Minamihachioji Hospital, Tokyo, Japan
                [d ]Department of Cardiology and Nephrology, Hirosaki University Graduate School of Medicine, Aomori, Japan
                [e ]Saiseikai Kumamoto Hospital, Kumamoto, Japan
                [f ]The Cardiovascular Institute, Tokyo, Japan
                [g ]Division of Biostatistics and Clinical Epidemiology, University of Toyama, Toyama, Japan
                Author notes
                [* ]Corresponding author at: Department of Internal Medicine and Cardiology, Nippon Medical School Tama-Nagayama Hospital, 1-7-1 Nagayama, Tama-shi, Tokyo 206-8512, Japan. kodani@ 123456nms.ac.jp
                Article
                S2352-9067(20)30131-7 100559
                10.1016/j.ijcha.2020.100559
                7298529
                150d28e2-a2d2-4e58-9c78-ccb29dcfc6af
                © 2020 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 26 March 2020
                : 1 June 2020
                Categories
                Original Paper

                atrial fibrillation,creatinine clearance,estimated glomerular filtration rate,thromboembolism,mortality

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