RESEARCH ARTICLE
Prevalence of Atrial Fibrillation and Antithrombotic Therapy in Hemodialysis Patients: Cross-Sectional Results of the Vienna InVestigation of AtriaL Fibrillation and Thromboembolism in Patients on HemoDIalysis (VIVALDI) a1111111111 a1111111111 a1111111111 a1111111111 a1111111111
OPEN ACCESS Citation: Ko¨nigsbru¨gge O, Posch F, Antlanger M, Kovarik J, Klauser-Braun R, Kletzmayr J, et al. (2017) Prevalence of Atrial Fibrillation and Antithrombotic Therapy in Hemodialysis Patients: Cross-Sectional Results of the Vienna InVestigation of AtriaL Fibrillation and Thromboembolism in Patients on HemoDIalysis (VIVALDI). PLoS ONE 12(1): e0169400. doi:10.1371/journal.pone.0169400 Editor: Juei-Tang Cheng, Chang Jung Christian University, TAIWAN Received: August 1, 2016 Accepted: November 27, 2016 Published: January 4, 2017 Copyright: © 2017 Ko¨nigsbru¨gge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Austrian law prohibits public availability of health-related personal data. Data are available upon reasonable request, submitted to Silvia Koder (silvia. [email protected]). Funding: Support was provided by O¨sterreichische Nationalbank Jubila¨umsfond (Austrian Nationbank Anniversary fund) grant number 16433 awarded to
Oliver Ko¨nigsbru¨gge1, Florian Posch1,2, Marlies Antlanger3, Josef Kovarik4, Renate Klauser-Braun5, Josef Kletzmayr5, Sabine Schmaldienst6, Martin Auinger7, Gu¨nther Zuntner8, Matthias Lorenz9, Ella Grilz1, Gerald Stampfel1, Stefan Steiner1, Ingrid Pabinger1, Marcus Sa¨emann3, Cihan Ay1,10* 1 Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria, 2 Department of Medicine, Clinical Division of Oncology, Medical University of Graz, Austria, 3 Clinical Division of Nephrology, Department of Medicine III, Medical University of Vienna, Vienna, Austria, 4 Department of Medicine VI, Wilhelminenspital, Vienna, Austria, 5 Department of Medicine III, Donauspital, Vienna, Austria, 6 Department of Medicine I, Kaiser-Franz-Josef-Spital, Vienna, Austria, 7 Department of Medicine III, Hietzing Hospital, Vienna, Austria, 8 Department of Medicine I, Rudolfstiftung Hospital, Vienna, Austria, 9 Vienna Dialysis Center, Vienna, Austria, 10 Department of Medicine, Thrombosis and Hemostasis Program, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America * [email protected]
Abstract Background Atrial fibrillation (AF) adds significant risk of stroke and thromboembolism in patients on hemodialysis (HD). The aim of this study was to investigate the prevalence of AF in a population-based cohort of HD patients and practice patterns of antithrombotic therapy for stroke prevention in AF.
Methods The Vienna InVestigation of AtriaL fibrillation and thromboembolism in patients on hemodialysis (VIVALDI), an ongoing prospective observational cohort study, investigates the prevalence of AF and the risk of thromboembolic events in HD patients in Vienna, Austria. We analyzed cross-sectional data of 626 patients (63.4% men, median age 66 years, approx. 73% of HD patients in Vienna), who provided informed consent. A structured interview with each patient was performed, recent and archived ECGs were viewed and medical histories were verified with electronic records.
PLOS ONE | DOI:10.1371/journal.pone.0169400 January 4, 2017
1 / 14
Prevalence of Atrial Fibrillation in Patients with Hemodialysis
IP [https://www.oenb.at/Ueber-Uns/ Forschungsfoerderung/Jubilaeumsfonds.html] and O¨sterreichische Gesellschaft fu¨r Innere Medizin (Austrian Society for Internal Medicine) JosephSkoda-Prize 2014 awarded to CA [http://www. oegim.at/aktuell/preise/josef-skodaprojektfoerderungspreis.html]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.
Results The overall prevalence of AF was 26.5% (166 patients, 71.1% men, median age 72 years) of which 57.8% had paroxysmal AF, 3.0% persistent AF, 32.5% permanent AF, and 6.6% of patients had newly diagnosed AF. The median CHA2DS2-VASc Score was 4 [25th-75th percentile 3–5]. In multivariable analysis, AF was independently associated with age (odds ratio: 1.05 per year increase, 95% confidence interval: 1.03–1.07), male sex (1.7, 1.1–2.6), history of venous thromboembolism (2.0, 1.1–3.6), congestive heart failure (1.7, 1.1–2.5), history of or active cancer (1.5, 1.0–2.4) and time on HD (1.08 per year on HD, 1.03–1.13). Antithrombotic treatment was applied in 84.4% of AF patients (anticoagulant agents in 29.5%, antiplatelet agents in 33.7%, and both in 21.1%). In AF patients, vitamin-K-antagonists were used more often than low-molecular-weight heparins (30.1% and 19.9%).
Conclusions The prevalence of AF is high amongst HD patients and is associated with age, sex, and distinct comorbidities. Practice patterns of antithrombotic treatment indicate a lack of consensus for stroke prevention in HD patients with AF.
Introduction Atrial fibrillation (AF) is a common cardiac arrhythmia that affects 1–2% of the general population, and increases the risk of stroke [1,2]. In patients with end-stage renal disease (ESRD) receiving hemodialysis (HD), AF is an underestimated comorbidity. Although it is recognized as a causal factor for thromboembolic ischemic stroke and is associated with increased mortality in HD patients [3,4], stroke prevention using antithrombotic agents is complicated by an excessive risk of bleeding in ESRD patients [5]. In the general population, stroke prevention in AF with oral anticoagulation with vitamin-K-antagonists (VKA) can reduce the incidence of stroke by 60% [6]. However, in HD patients there is currently no clear evidence for how to achieve stroke prevention [7], and large differences exists in the current practice for use of antithrombotic agents in HD patients [8]. The reported prevalence of AF in HD patients is 3.8 to 27% [9–14]. This large variability in AF prevalence may be explained by regional differences [8], but may also be biased by the different study designs and data capture methods. The overall higher prevalence of AF compared to the general population is hypothesized to be associated with the HD procedure itself,[15] which can lead to an increase of cardiac dimensions and decrease of ejection fraction, resulting in AF development [12]. Thus, the prevalence of AF in HD patients may depend upon hemodialysis-specific patient characteristics as well as on treatment modalities. In this population-based cohort of HD patients, we investigated the prevalence of AF, analyzed the association of AF with clinico-epidemiological factors, and collected data on practice patterns of antithrombotic treatment strategies applied in HD patients for stroke prevention in AF.
Patients and Methods The Vienna InVestigation of AtriaL fibrillation and thromboembolism in hemDIialysis patients (VIVALDI) is a cohort study with aims to gather population-based epidemiologic data on the prevalence of AF, thromboembolic events and use of antithrombotic treatments in
PLOS ONE | DOI:10.1371/journal.pone.0169400 January 4, 2017
2 / 14
Prevalence of Atrial Fibrillation in Patients with Hemodialysis
HD patients and prospective data on the incidence of stroke and thromboembolism, as well as the incidence of new AF, bleeding, hospitalization, cardiovascular events, thrombotic shunt complications, and mortality. The study consists of a cross-sectional baseline investigation and a prospective observational evaluation of study outcomes and has approval of the local ethics committees. VIVALDI is conducted in accordance with the declaration of Helsinki and its later amendments. Patient treated at the seven major HD centers in the city of Vienna, Austria, were eligible for recruitment. The study cohort was recruited between April 2014 and July 2015. Patients aged 18 years or above, with an independent diagnosis of ESRD requiring long-term ambulatory HD treatment, able to provide signed and dated informed consent, and willing to comply with all study procedures were eligible for inclusion. Patients were excluded, if they were pregnant, lactating, suspected of pregnancy, incapable to consent, hospitalized as an in-patient, or serving a prison term at the time of enrolment. The steps of patient enrolment and corresponding patient numbers are provided in Fig 1. Out of approximately 860 patients receiving HD in Vienna (population of 1.7 million in 2014–2015), Austria, 814 (94.6%) were personally approached and 626 patients (~73% of the total HD population in the city) met the inclusion criteria and consented to participate. The prospective observation period is still ongoing. A trained study investigator interviewed each patient individually and recorded demographics, medical histories and HD parameters using the REDCap electronic data capture tools hosted at the Medical University of Vienna, Department of Medicine I, Clinical Division of Hematology and Haemostaseology [16]. Data quality was verified with treating nephrologists and the medical documentation of the participating dialysis centers. Cause of ESRD was established from the medical records at the dialysis center and classified according to categories of the Austrian Dialysis and Transplantation Registry [17]. A diagnosis of AF was recorded for symptomatic or asymptomatic AF in any one of the following (1) signs of AF on a recent 12-lead resting ECG within one month of recruitment, (2) documented AF episode during previous ECGs conducted routinely or in case of arrhythmia at the dialysis centers, or (3) recorded diagnosis of AF in medical records. Recently diagnosed AF was defined as recent new diagnosis of AF, where a specific type had not been established. Paroxysmal AF is recurrent self-terminating AF. Persistent AF is long-lasting AF that requires termination by cardioversion. In permanent AF, patients do not return to sinus rhythm or attempt cardioversion [18]. Time on HD was calculated as the sum of the current HD treatment period and periods of HD treatment before renal transplant in patients where applicable. Inter-dialytic weight gain was calculated as the difference between pre-dialysis weight and target dry body weight. A history of venous thromboembolism only includes non-catheter-associated deep vein thrombosis and pulmonary embolism.
Statistical methods Descriptive parameters of the study population are given as absolute and relative frequencies or median values with 25th to 75th percentile, where appropriate. In order to compare the distribution of patient parameters between patients with and without AF, the dependent variable, we used the Mann-Whitney U test for ordinal and continuous independent variables or chisquared test for categorical independent variables, where applicable. The odds ratios (OR) for association between AF and patient characteristics and comorbidities were calculated in univariable and multivariable logistic regression models. A two-tailed p-value below 0.05 was regarded as statistically significant. All calculations were conducted with SPSS (IBM SPSS for Windows, Version 23.0. Armonk, NY) and graphs were drawn with GraphPad Prism (GraphPad Software, Version 5.00 for Windows, San Diego CA).
PLOS ONE | DOI:10.1371/journal.pone.0169400 January 4, 2017
3 / 14
Prevalence of Atrial Fibrillation in Patients with Hemodialysis
Fig 1. Flow chart of the patient recruitment. doi:10.1371/journal.pone.0169400.g001
Results Study population A total of 626 patients were recruited into the study, of which 397 (63.4%) were men. The median age was 66 years (25th to 75th percentile 55–75) and the median BMI was 25.7 kg/m2 (22.4–29.6). Diabetic nephropathy was the most frequent cause for ESRD (25.6%) followed by vascular nephropathy (19.3%). Further baseline characteristics of the study cohort are provided in Table 1.
PLOS ONE | DOI:10.1371/journal.pone.0169400 January 4, 2017
4 / 14
Prevalence of Atrial Fibrillation in Patients with Hemodialysis
Table 1. Characteristics of the study population at baseline. Full cohort
Non-AF cohort
AF cohort
Patients, n (%)
626 (100)
460 (73.5)
166 (26.5)
p-value*
Male sex (%)
397 (63.4)
279 (60.7)
118 (71.1)
0.017
Prevalence of Atrial Fibrillation and Antithrombotic Therapy in Hemodialysis Patients: Cross-Sectional Results of the Vienna InVestigation of AtriaL Fibrillation and Thromboembolism in Patients on HemoDIalysis (VIVALDI) a1111111111 a1111111111 a1111111111 a1111111111 a1111111111
OPEN ACCESS Citation: Ko¨nigsbru¨gge O, Posch F, Antlanger M, Kovarik J, Klauser-Braun R, Kletzmayr J, et al. (2017) Prevalence of Atrial Fibrillation and Antithrombotic Therapy in Hemodialysis Patients: Cross-Sectional Results of the Vienna InVestigation of AtriaL Fibrillation and Thromboembolism in Patients on HemoDIalysis (VIVALDI). PLoS ONE 12(1): e0169400. doi:10.1371/journal.pone.0169400 Editor: Juei-Tang Cheng, Chang Jung Christian University, TAIWAN Received: August 1, 2016 Accepted: November 27, 2016 Published: January 4, 2017 Copyright: © 2017 Ko¨nigsbru¨gge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Austrian law prohibits public availability of health-related personal data. Data are available upon reasonable request, submitted to Silvia Koder (silvia. [email protected]). Funding: Support was provided by O¨sterreichische Nationalbank Jubila¨umsfond (Austrian Nationbank Anniversary fund) grant number 16433 awarded to
Oliver Ko¨nigsbru¨gge1, Florian Posch1,2, Marlies Antlanger3, Josef Kovarik4, Renate Klauser-Braun5, Josef Kletzmayr5, Sabine Schmaldienst6, Martin Auinger7, Gu¨nther Zuntner8, Matthias Lorenz9, Ella Grilz1, Gerald Stampfel1, Stefan Steiner1, Ingrid Pabinger1, Marcus Sa¨emann3, Cihan Ay1,10* 1 Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria, 2 Department of Medicine, Clinical Division of Oncology, Medical University of Graz, Austria, 3 Clinical Division of Nephrology, Department of Medicine III, Medical University of Vienna, Vienna, Austria, 4 Department of Medicine VI, Wilhelminenspital, Vienna, Austria, 5 Department of Medicine III, Donauspital, Vienna, Austria, 6 Department of Medicine I, Kaiser-Franz-Josef-Spital, Vienna, Austria, 7 Department of Medicine III, Hietzing Hospital, Vienna, Austria, 8 Department of Medicine I, Rudolfstiftung Hospital, Vienna, Austria, 9 Vienna Dialysis Center, Vienna, Austria, 10 Department of Medicine, Thrombosis and Hemostasis Program, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America * [email protected]
Abstract Background Atrial fibrillation (AF) adds significant risk of stroke and thromboembolism in patients on hemodialysis (HD). The aim of this study was to investigate the prevalence of AF in a population-based cohort of HD patients and practice patterns of antithrombotic therapy for stroke prevention in AF.
Methods The Vienna InVestigation of AtriaL fibrillation and thromboembolism in patients on hemodialysis (VIVALDI), an ongoing prospective observational cohort study, investigates the prevalence of AF and the risk of thromboembolic events in HD patients in Vienna, Austria. We analyzed cross-sectional data of 626 patients (63.4% men, median age 66 years, approx. 73% of HD patients in Vienna), who provided informed consent. A structured interview with each patient was performed, recent and archived ECGs were viewed and medical histories were verified with electronic records.
PLOS ONE | DOI:10.1371/journal.pone.0169400 January 4, 2017
1 / 14
Prevalence of Atrial Fibrillation in Patients with Hemodialysis
IP [https://www.oenb.at/Ueber-Uns/ Forschungsfoerderung/Jubilaeumsfonds.html] and O¨sterreichische Gesellschaft fu¨r Innere Medizin (Austrian Society for Internal Medicine) JosephSkoda-Prize 2014 awarded to CA [http://www. oegim.at/aktuell/preise/josef-skodaprojektfoerderungspreis.html]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.
Results The overall prevalence of AF was 26.5% (166 patients, 71.1% men, median age 72 years) of which 57.8% had paroxysmal AF, 3.0% persistent AF, 32.5% permanent AF, and 6.6% of patients had newly diagnosed AF. The median CHA2DS2-VASc Score was 4 [25th-75th percentile 3–5]. In multivariable analysis, AF was independently associated with age (odds ratio: 1.05 per year increase, 95% confidence interval: 1.03–1.07), male sex (1.7, 1.1–2.6), history of venous thromboembolism (2.0, 1.1–3.6), congestive heart failure (1.7, 1.1–2.5), history of or active cancer (1.5, 1.0–2.4) and time on HD (1.08 per year on HD, 1.03–1.13). Antithrombotic treatment was applied in 84.4% of AF patients (anticoagulant agents in 29.5%, antiplatelet agents in 33.7%, and both in 21.1%). In AF patients, vitamin-K-antagonists were used more often than low-molecular-weight heparins (30.1% and 19.9%).
Conclusions The prevalence of AF is high amongst HD patients and is associated with age, sex, and distinct comorbidities. Practice patterns of antithrombotic treatment indicate a lack of consensus for stroke prevention in HD patients with AF.
Introduction Atrial fibrillation (AF) is a common cardiac arrhythmia that affects 1–2% of the general population, and increases the risk of stroke [1,2]. In patients with end-stage renal disease (ESRD) receiving hemodialysis (HD), AF is an underestimated comorbidity. Although it is recognized as a causal factor for thromboembolic ischemic stroke and is associated with increased mortality in HD patients [3,4], stroke prevention using antithrombotic agents is complicated by an excessive risk of bleeding in ESRD patients [5]. In the general population, stroke prevention in AF with oral anticoagulation with vitamin-K-antagonists (VKA) can reduce the incidence of stroke by 60% [6]. However, in HD patients there is currently no clear evidence for how to achieve stroke prevention [7], and large differences exists in the current practice for use of antithrombotic agents in HD patients [8]. The reported prevalence of AF in HD patients is 3.8 to 27% [9–14]. This large variability in AF prevalence may be explained by regional differences [8], but may also be biased by the different study designs and data capture methods. The overall higher prevalence of AF compared to the general population is hypothesized to be associated with the HD procedure itself,[15] which can lead to an increase of cardiac dimensions and decrease of ejection fraction, resulting in AF development [12]. Thus, the prevalence of AF in HD patients may depend upon hemodialysis-specific patient characteristics as well as on treatment modalities. In this population-based cohort of HD patients, we investigated the prevalence of AF, analyzed the association of AF with clinico-epidemiological factors, and collected data on practice patterns of antithrombotic treatment strategies applied in HD patients for stroke prevention in AF.
Patients and Methods The Vienna InVestigation of AtriaL fibrillation and thromboembolism in hemDIialysis patients (VIVALDI) is a cohort study with aims to gather population-based epidemiologic data on the prevalence of AF, thromboembolic events and use of antithrombotic treatments in
PLOS ONE | DOI:10.1371/journal.pone.0169400 January 4, 2017
2 / 14
Prevalence of Atrial Fibrillation in Patients with Hemodialysis
HD patients and prospective data on the incidence of stroke and thromboembolism, as well as the incidence of new AF, bleeding, hospitalization, cardiovascular events, thrombotic shunt complications, and mortality. The study consists of a cross-sectional baseline investigation and a prospective observational evaluation of study outcomes and has approval of the local ethics committees. VIVALDI is conducted in accordance with the declaration of Helsinki and its later amendments. Patient treated at the seven major HD centers in the city of Vienna, Austria, were eligible for recruitment. The study cohort was recruited between April 2014 and July 2015. Patients aged 18 years or above, with an independent diagnosis of ESRD requiring long-term ambulatory HD treatment, able to provide signed and dated informed consent, and willing to comply with all study procedures were eligible for inclusion. Patients were excluded, if they were pregnant, lactating, suspected of pregnancy, incapable to consent, hospitalized as an in-patient, or serving a prison term at the time of enrolment. The steps of patient enrolment and corresponding patient numbers are provided in Fig 1. Out of approximately 860 patients receiving HD in Vienna (population of 1.7 million in 2014–2015), Austria, 814 (94.6%) were personally approached and 626 patients (~73% of the total HD population in the city) met the inclusion criteria and consented to participate. The prospective observation period is still ongoing. A trained study investigator interviewed each patient individually and recorded demographics, medical histories and HD parameters using the REDCap electronic data capture tools hosted at the Medical University of Vienna, Department of Medicine I, Clinical Division of Hematology and Haemostaseology [16]. Data quality was verified with treating nephrologists and the medical documentation of the participating dialysis centers. Cause of ESRD was established from the medical records at the dialysis center and classified according to categories of the Austrian Dialysis and Transplantation Registry [17]. A diagnosis of AF was recorded for symptomatic or asymptomatic AF in any one of the following (1) signs of AF on a recent 12-lead resting ECG within one month of recruitment, (2) documented AF episode during previous ECGs conducted routinely or in case of arrhythmia at the dialysis centers, or (3) recorded diagnosis of AF in medical records. Recently diagnosed AF was defined as recent new diagnosis of AF, where a specific type had not been established. Paroxysmal AF is recurrent self-terminating AF. Persistent AF is long-lasting AF that requires termination by cardioversion. In permanent AF, patients do not return to sinus rhythm or attempt cardioversion [18]. Time on HD was calculated as the sum of the current HD treatment period and periods of HD treatment before renal transplant in patients where applicable. Inter-dialytic weight gain was calculated as the difference between pre-dialysis weight and target dry body weight. A history of venous thromboembolism only includes non-catheter-associated deep vein thrombosis and pulmonary embolism.
Statistical methods Descriptive parameters of the study population are given as absolute and relative frequencies or median values with 25th to 75th percentile, where appropriate. In order to compare the distribution of patient parameters between patients with and without AF, the dependent variable, we used the Mann-Whitney U test for ordinal and continuous independent variables or chisquared test for categorical independent variables, where applicable. The odds ratios (OR) for association between AF and patient characteristics and comorbidities were calculated in univariable and multivariable logistic regression models. A two-tailed p-value below 0.05 was regarded as statistically significant. All calculations were conducted with SPSS (IBM SPSS for Windows, Version 23.0. Armonk, NY) and graphs were drawn with GraphPad Prism (GraphPad Software, Version 5.00 for Windows, San Diego CA).
PLOS ONE | DOI:10.1371/journal.pone.0169400 January 4, 2017
3 / 14
Prevalence of Atrial Fibrillation in Patients with Hemodialysis
Fig 1. Flow chart of the patient recruitment. doi:10.1371/journal.pone.0169400.g001
Results Study population A total of 626 patients were recruited into the study, of which 397 (63.4%) were men. The median age was 66 years (25th to 75th percentile 55–75) and the median BMI was 25.7 kg/m2 (22.4–29.6). Diabetic nephropathy was the most frequent cause for ESRD (25.6%) followed by vascular nephropathy (19.3%). Further baseline characteristics of the study cohort are provided in Table 1.
PLOS ONE | DOI:10.1371/journal.pone.0169400 January 4, 2017
4 / 14
Prevalence of Atrial Fibrillation in Patients with Hemodialysis
Table 1. Characteristics of the study population at baseline. Full cohort
Non-AF cohort
AF cohort
Patients, n (%)
626 (100)
460 (73.5)
166 (26.5)
p-value*
Male sex (%)
397 (63.4)
279 (60.7)
118 (71.1)
0.017
