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      Ticagrelor vs. Clopidogrel in Acute Coronary Syndrome Patients With Chronic Kidney Disease After New-Generation Drug-Eluting Stent Implantation

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          Abstract

          Background: The impact of ticagrelor-based dual antiplatelet therapy (DAPT) on acute coronary syndrome (ACS) in patients with chronic kidney disease (CKD) remains unclear.

          Methods: Data on a total of 1,067 ACS patients with CKD including end-stage renal disease (ESRD) who underwent new-generation drug-eluting stent implantation were extracted from a multicenter registry. This study aimed to compare outcomes of patients treated with ticagrelor- ( n = 449) and those treated with clopidogrel-based ( n = 618) DAPT. Outcomes of interest included major adverse cardiac and cerebrovascular events (MACCEs) and bleeding (Bleeding Academic Research Consortium grade 3 or 5) at 12 months. Propensity-score matching (346 pairs) analysis was performed.

          Results: The patients with ESRD showed the highest MACCE and bleeding rates ( P < 0.001). There was no difference in the rate of MACCEs between the treatment groups (7.8% vs. 8.4%; hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.56–1.61, P = 0.855); however, a trend toward an increased bleeding rate was observed in the ticagrelor-based DAPT group (6.8% vs. 3.8%, HR = 1.84, 95% CI = 0.93–3.63, P = 0.079). Among patients with CKD stage III/IV but without ESRD (277 pairs), the ticagrelor-based DAPT group showed a reduced MACCE rate (3.6% vs. 8.7%, HR = 0.41, 95% CI = 0.19–0.86, P = 0.018) and a similar bleeding rate (5.1% vs. 3.2%, HR = 1.61, 95% CI = 0.70–3.71, P = 0.267), compared with those of the clopidogrel-based DAPT group.

          Conclusion: The effects of ticagrelor-based DAPT on ischemic and bleeding outcomes of ACS patients with CKD varied according to CKD stage; in ACS patients with CKD without ESRD, ticagrelor-based DAPT reduced MACCE risk without increasing bleeding risks, relative to those observed with clopidogrel-based DAPT.

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          Most cited references24

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          A new equation to estimate glomerular filtration rate.

          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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            Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.

            End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined. We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization. The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1.1 to 1.2), 1.8 with an estimated GFR of 30 to 44 ml per minute per 1.73 m2 (95 percent confidence interval, 1.7 to 1.9), 3.2 with an estimated GFR of 15 to 29 ml per minute per 1.73 m2 (95 percent confidence interval, 3.1 to 3.4), and 5.9 with an estimated GFR of less than 15 ml per minute per 1.73 m2 (95 percent confidence interval, 5.4 to 6.5). The adjusted hazard ratio for cardiovascular events also increased inversely with the estimated GFR: 1.4 (95 percent confidence interval, 1.4 to 1.5), 2.0 (95 percent confidence interval, 1.9 to 2.1), 2.8 (95 percent confidence interval, 2.6 to 2.9), and 3.4 (95 percent confidence interval, 3.1 to 3.8), respectively. The adjusted risk of hospitalization with a reduced estimated GFR followed a similar pattern. An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community-based population. These findings highlight the clinical and public health importance of chronic renal insufficiency. Copyright 2004 Massachusetts Medical Society
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              2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC).

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                Author and article information

                Contributors
                Journal
                Front Cardiovasc Med
                Front Cardiovasc Med
                Front. Cardiovasc. Med.
                Frontiers in Cardiovascular Medicine
                Frontiers Media S.A.
                2297-055X
                10 January 2022
                2021
                : 8
                : 707722
                Affiliations
                [1] 1Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Yongin Severance Hospital , Yongin, South Korea
                [2] 2Department of Cardiology, The Catholic University College of Medicine, Bucheon St. Mary's Hospital , Bucheon, South Korea
                [3] 3Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Cardiovascular Hospital , Seoul, South Korea
                [4] 4Department of Cardiology, CHA Bundang Medical Centre, CHA University , Seongnam, South Korea
                Author notes

                Edited by: Tommaso Gori, Johannes Gutenberg University Mainz, Germany

                Reviewed by: Matteo Nardin, Civil Hospital of Brescia, Italy; Monica Verdoia, University of Eastern Piedmont, Italy

                *Correspondence: Byeong-Keuk Kim kimbk@ 123456yuhs.ac

                This article was submitted to Coronary Artery Disease, a section of the journal Frontiers in Cardiovascular Medicine

                †These authors have contributed equally to this work and share first authorship

                Article
                10.3389/fcvm.2021.707722
                8785207
                35083294
                097dc52c-e873-486d-97e5-7f91033a71e0
                Copyright © 2022 Roh, Lee, Kim, Hong, Kim, Ahn, Cho, Kim, Ko, Choi, Hong and Jang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 May 2021
                : 15 December 2021
                Page count
                Figures: 5, Tables: 3, Equations: 0, References: 24, Pages: 11, Words: 5979
                Categories
                Cardiovascular Medicine
                Original Research

                ticagrelor,clopidogrel,acute coronary syndrome,renal insufficiency,drug eluting stents

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