Elsevier

Thrombosis Research

Volume 128, Issue 4, October 2011, Pages 341-345
Thrombosis Research

Regular Article
Glomerular filtration rate in patients with atrial fibrillation on warfarin treatment: A subgroup analysis from the AURICULA registry in Sweden

https://doi.org/10.1016/j.thromres.2011.04.022Get rights and content

Abstract

Introduction

Numerous associations between chronic kidney disease (CKD) and atrial fibrillation (AF) have been reported and patients with CKD on anticoagulation therapy have an increased risk of bleeding. Currently, new anticoagulant agents are emerging in clinical practice, some of which are excreted by the kidneys. The proportion of AF patients on anticoagulant treatment with reduced renal function is, however, unknown.

Materials and Methods

Using AURICULA, a Swedish registry for anticoagulation, estimated glomerular filtration rate (eGFR) was investigated in AF patients on warfarin treatment (n = 2,603). The study group was compared with a healthy sample from the population (n = 2,261). Two different creatinine prediction equations were used for calculating eGFR: the Lund-Malmö (LM) and MDRD Study equation.

Results

The fraction of AF patients with eGFR < 30 and < 45 ml/min/1.73 m2 were 8.1% and 22.9% with the LM and 4.3% and 16.3% with the MDRD equation, respectively, and significantly higher than corresponding values in the reference population. GFR decreased with increasing age, where 11.4% and 5.6% of AF patients aged  75 years had eGFR < 30 ml/min/1.73 m2 according to the LM and MDRD equations, respectively.

Conclusions

Severe renal impairment is common among AF patients on anticoagulant treatment with warfarin, especially at higher ages. Monitoring of renal function should be implemented in clinical practice for AF patients treated with new anticoagulants eliminated by the kidneys.

Introduction

Patients with atrial fibrillation (AF) are frequently present in healthcare settings. Similar to a general western population, the AF prevalence in Sweden is approximately 1 to 1.5% [1], [2]. During the past decade, a large number of published works have demonstrated associations between kidney dysfunction and cardiovascular disease (CVD) [3], [4], [5], [6]. In recent years, a relationship between end-stage renal disease (ESRD) [7], [8] as well as mild to moderate chronic kidney disease (CKD) [9], [10], [11], [12], [13], [14], [15], [16] and AF has been reported. The newly introduced “cardiorenal syndrome” divides causal links between AF and CKD into three categories: heart diseases leading to kidney disease, kidney diseases leading to heart disease and systemic conditions leading to both heart and kidney disease [17]. Although research in this area is under way, there is still more to learn about correlations, cause-and-effect relationships and pathological mechanisms between CKD and AF.

Patients with CKD have impaired platelet function [18]. Despite this fact, CKD is a risk factor for thrombotic events [18], [19]. Paradoxically, this patient group is also at greater risk for bleeding complications [18], which is emphasized by including CKD in schemes for predicting hemorrhage [20]. As AF patients age, the probability of comorbidities increases, thus leading to an extended need for various pharmaceuticals [21]. Because many drugs are eliminated by the kidneys, patients with moderate to severe renal impairment are often excluded from pharmacological studies [22]. Currently, new anticoagulant agents such as dabigatran etexilate and rivaroxaban, which are excreted by the kidneys, are emerging in clinical practice [22], [23]. To our knowledge, the proportion of AF patients on anticoagulant treatment exhibiting chronic kidney disease (CKD) and potential contraindications to pharmacological treatment is unknown. In the present study, we compared estimated GFR (eGFR) in AF patients on anticoagulation treatment with warfarin (Waran®, Nycomed AB, Stockholm, Sweden) to a healthy reference group sampled from the population. Two different creatinine predicting equations were used to estimate GFR. We hypothesized a large proportion of the AF group to have an eGFR < 30 ml/min/1.73 m2 and that AF patients would differ from the reference group in terms of renal function.

Section snippets

Study population

The study population consisted of AF patients on anticoagulation treatment with warfarin. Patients were collected from AURICULA, a national quality registry for Swedish patients on anticoagulant treatment (www.ucr.uu.se/auricula/index.php). AURICULA was introduced in 2006 with aims to improve and modernize anticoagulant treatment and evaluate the patient benefit of such modifications. Among approximately 25,000 AURICULA patients eligible at June 1st, 2009, all 4,298 subjects enrolled in the

Results

Characteristics of the 2,603 AF patients and the 2,261 reference subjects are presented in Table 1. Indication for warfarin treatment was primary prophylaxis in 83.2% and secondary prophylaxis in 16.8% of the AF patients. In addition to AF, 133 of the patients had heart valve prosthesis and 70 had previous venous thromboembolism (data not shown). The mean age in the AF group and the reference population was 75.4 ± 10.2 and 70.8 ± 9.6 years (Table 1) and the proportion of women was 42.6% and 54.4%,

Discussion

This study investigates renal function among AF patients on anticoagulation treatment with warfarin. The results suggest that around one-tenth of AF patients have severely impaired renal function defined as an eGFR < 30 ml/min/1.73 m2 and that this proportion increases with age. Compared to a healthy reference population, a significant difference in the prevalence of decreased kidney function was seen. Almost 50% of AF patients in this study have eGFR < 60 ml/min/1.73 m2, which corresponds to stage

Conflict of interest statement

Prof. Gunnar Engström is employed as senior epidemiologist by AstraZeneca R&D.

Acknowledgements

This study was supported by an unrestricted grant form Bergers Stiftelse and funds from the Skåne University Hospital, Malmö. The authors would like to thank Camilla Nilsson and Leif Persson, both at Skåne University Hospital, Malmö, Sweden.

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