Association of Different Estimates of Renal Function With Cardiovascular Mortality and Bleeding in Atrial Fibrillation.


Background We compared different methods of estimated glomerular filtration rate (eGFR) and their association with cardiovascular death and major bleeding in 14 980 patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Methods and Results eGFR was calculated using equations based on creatinine (Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) and/or cystatin C (CKD-EPICysC and CKD-EPICysC+Creatinine). These 5 eGFR equations, as well as the individual variables that are used in these equations, were assessed for correlation and discriminatory ability for cardiovascular death and major bleeding. The median age was 70.0 years, and 35.6% were women. The median eGFR was highest with Cockcroft-Gault (74.1 mL/min) and CKD-EPICysC (74.2 mL/min), and lowest with Modification of Diet in Renal Disease (66.5 mL/min). Correlation between methods ranged from 0.49 (Cockroft-Gault and CKD-EPICysC) to 0.99 (Modification of Diet in Renal Disease and CKD-EPI). Among the eGFR equations, those based on cystatin C yielded the highest C indices for cardiovascular death and major bleeding: 0.628 (CKD-EPICysC) and 0.612 (CKD-EPICysC+Creatinine), respectively. A model based on the variables within the different eGFR equations (age, sex, weight, creatinine, and cystatin C) yielded the highest discriminatory value for both outcomes, with a C index of 0.673 and 0.656, respectively. Conclusions In patients with atrial fibrillation on anticoagulation, correlation between eGFR calculated using different methods varied substantially. Cystatin C-based eGFRs seem to provide the most robust information for predicting death and bleeding. A model based on the individual variables within the eGFR equations, however, provided the highest discriminatory value. Our findings may help refine risk stratification in patients with atrial fibrillation and define how renal function should be determined in future atrial fibrillation studies. Registration URL: https://www.clini​caltr​; Unique identifier: NCT00412984.





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Publication Info

Hijazi, Ziad, Christopher B Granger, Stefan H Hohnloser, Johan Westerbergh, Johan Lindbäck, John H Alexander, Matyas Keltai, Alexander Parkhomenko, et al. (2020). Association of Different Estimates of Renal Function With Cardiovascular Mortality and Bleeding in Atrial Fibrillation. Journal of the American Heart Association, 9(18). p. e017155. 10.1161/jaha.120.017155 Retrieved from

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Christopher Bull Granger

Donald F. Fortin, M.D. Distinguished Professor of Medicine

My primary research interest is in conduct and methodology of large randomized clinical trials in heart disease. I have led a number of large international clinical studies in heart attacks, unstable angina, heart failure, and atrial fibrillation. I have lead clinical studies of blood thinners and coronary intervention for heart attacks, stroke prevention in atrial fibrillation, and prevention of heart attack for patients with coronary artery disease. I have been co-director of the Reperfusion of Acute MI in Carolina Emergency Departments (RACE) project that is a North Carolina state-wide program to improve reperfusion care for acute myocardial infarction. I serve as the Chairman of the American Heart Association Mission: Lifeline program to improve heart attack care nationally as well as the American College of Cardiology/American Heart Association guideline committee for heart attack care. I have also studied the effects of genetic variation on heart disease. I work with the National Institute of Health and the Federal Drug Administration on evaluation of heart disease and of new drugs. I have developed tools to predict which patients are at risk for death, heart attack, and need for hospitalization.


John Hunter Peel Alexander

Professor of Medicine

John H. Alexander, MD, MHS is a cardiologist and Professor of Medicine in the Department of Medicine, Division of Cardiology at Duke University School of Medicine, as well as the Vice Chief, Clinical Research in the Division of Cardiology. He is the Director of Cardiovascular Research at the Duke Clinical Research Institute where he oversees a large group of clinical research faculty and a broad portfolio of cardiovascular clinical trials and observational clinical research programs. He is a member of the American Society of Clinical Investigation.

Dr. Alexander’s clinical interests are in acute and general cardiovascular disease, valvular heart disease, and echocardiology. His research is focused on the translation of novel therapeutic concepts into clinical data through clinical trials, specifically on the therapeutics of acute coronary syndromes, chronic coronary artery disease, and cardiac surgery and on novel methodological approaches to clinical trials. He was on the Executive Committee of the ARISTOTLE trial of apixaban in patients with atrial fibrillation and was the Principal Investigator of the APPRAISE-2 trial of apixaban in patients with acute coronary syndromes.

Dr. Alexander has published extensively and has served as the principal investigator of numerous multicenter clinical trials. He currently serves as the co-chair of the Clinical Trial Transformation Initiative (CTTI).


Renato Delascio Lopes

Professor of Medicine

Atrial Fibrillation
Antithrombotic Therapy in patients with Acute Coronary Syndromes
Elderly patients with Heart Disease
Biomarkers in Acute Coronary Syndromes and Atrial Fibrillation
Thrombosis and Anticoagulation and novel antithrombotic agents
Metabolomics in Cardiovascular Medicine

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