Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation

Genovesi, Simonetta; Rossi, Emanuela; Gallieni, Maurizio; Stella, Andréa; Badiali, Fabio; Conte, Ferruccio; Pasquali, Sonia; Bertoli, Silvio; Ondei, Patrizia; Bonforte, Giuseppe; Pozzi, Claudio; Rebora, Paola; Valsecchi, Maria Grazia; Santoro, Antonio

doi:10.1093/ndt/gfu334

Cited by 99 publications

(116 citation statements)

References 26 publications

(40 reference statements)

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“…161 Such concerns are particularly relevant because observational studies have shown no association between warfarin use and averted stroke in patients with severe CKD. 160,[162][163][164] Available data suggest that the efficacy of rivaroxaban, dabigatran, apixaban, and edoxaban is comparable to that of warfarin and that they can be safely used in people with stage 3 CKD. Rivaroxaban, dabigatran, and apixaban are approved for use in the United States in people with stage 4 CKD, and apixaban is approved for use in dialysis patients, all on the basis of pharmacokinetic data without any evidence of clinical efficacy or safety.…”

Section: Atrial Fibrillationmentioning

confidence: 99%

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

2016

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Abstract-Patients with chronic kidney disease and end-stage renal disease are at 5-to 10-fold higher risk for developing cardiovascular disease (CVD) than age-matched controls. Clinically, CVD in this population manifests as coronary artery disease, arrhythmias, stroke, or congestive heart failure. Beyond the traditional risk factors (eg, diabetes mellitus and hypertension), uremia-specific factors that arise from accumulating toxins also contribute to the pathogenesis of CVD.In this review, we summarize the literature on the epidemiology of both traditional and uremia-related CVD and focus on postulated mechanisms of the latter. P. Jousset, MD, 1 describing common causes of death among patients with Bright disease C hronic kidney disease (CKD) is an increasingly urgent public health concern that is projected to grow worldwide at a rate of 8% annually, with the fastest growth expected in developing nations.2,3 It has long been known that patients with kidney failure are predisposed to cardiovascular disease (CVD) that manifests clinically in various forms, including coronary artery disease, atrial or ventricular arrhythmias, myocardial infarction, stroke, or congestive heart failure. Over the last 30 years, it has become clear that the risk of CVD increases early in the course of progressive kidney disease and that the epidemiology, pathophysiology, prevention, and treatment of CVD and CKD are closely related and interdependent. 4 In this review, we initially describe the epidemiology of CVD among people with CKD, noting the limitations of available research. We then discuss common risk factors for CVD (traditional and nontraditional) and key shared aspects of its pathophysiology with CKD. Next we describe emerging diagnostic tools and novel therapies that may help to delay or prevent end-stage renal disease (ESRD) and to curtail the escalating burden of cardiorenal disease. In the final section, we discuss the health services and health policy challenges that CKD and its inextricably linked CVD morbidities pose worldwide, particularly for low-and middle-income countries (LMICs). Phenotypes and Epidemiology of CVD in Patients With CKDPatients with CKD and some forms of CVD share a number of risk factors and underlying pathophysiological mechanisms that, by virtue of their similarities, offer opportunities to improve their management. The epidemiology of 4 of the commonest clinical phenotypes of CVD associated with CKD is discussed below. Coronary Artery DiseaseCoronary artery disease (CAD) is a leading cause of death among people with advanced CKD. Clinical syndromes compatible with CAD (including angina and myocardial infarction) are exceedingly common in patients with nondialysis-dependent CKD, and the incidence of myocardial

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Section: Atrial Fibrillationmentioning

confidence: 99%

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

2016

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“…However, differences in study design might also play a significant role. Previous studies enrolled incident HD patients [14][15][16]23] who have higher mortality rates in the first weeks of treatment, screened for eligibility only those hospitalized for a cardiac event [17], and enrolled patients with pre-existing AF [16,22] , two potential sources of selection bias.…”

Section: Discussionmentioning

confidence: 99%

Patients' Characteristics Affect the Survival Benefit of Warfarin Treatment for Hemodialysis Patients with Atrial Fibrillation. A Historical Cohort Study

Brancaccio

Neri²,

Bellocchio³

et al. 2016

Am J Nephrol

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Background: Stroke prevention in dialysis-dependent patients with atrial fibrillation (AF) is an unresolved clinical dilemma. Indeed, no randomized controlled trial evaluating the efficacy and safety of oral anticoagulants in this population, has been conducted so far. Observational research on the use of warfarin in patients on dialysis has shown conflicting results. This uncertainty is mirrored by the wide variations in warfarin prescription patterns across centers. We sought to evaluate the association between the use of vitamin K antagonists (VKAs) and mortality among hemodialysis patient with AF and to assess potential factors affecting the risk-benefit profile of warfarin in this population. Methods: A total of 91,987 patients registered in the European Clinical Dialysis Database® system from January 2004 to January 2015. Of which, 9,238 patients were identified with a diagnosis of AF. After excluding ineligible patients, a 1:1 propensity score matched cohort of 1,324 warfarin users and non-users were assembled. Results: VKA use was associated with both increased 90-day survival (hazard ratio, HR 0.47, p < 0.01) and 6-year survival (HR 0.76, p < 0.01); however, a trend indicated a stronger early benefit (p for time-interaction <0.01). Moderation analysis showed that patients' age and clinical history of stroke strongly influenced warfarin-related benefits on survival. Conclusion: VKA may provide an early survival benefit; however, this is partially offset later during the follow-up. In addition, heterogeneous risk-benefit profiles were observed among subgroups of dialysis-dependent patients with AF, further emphasizing the complexities of tailoring stroke prevention strategies in this population.

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“…This turns into a low prevalence of warfarin prescription (less than 50% of the patients) [27]. In this specific setting characterized by a very high mortality, anticoagulation seems to be associated with a better survival; furthermore, patients with the highest time of International Normalized Ratio (INR) in therapeutic range had the lowest bleeding rate [28].…”

Section: Estimation Of Renal Functionmentioning

confidence: 99%

Dabigatran etexilate: appropriate use in patients with chronic kidney disease and in the elderly patients

Molteni

Minno

et al. 2017

Intern Emerg Med

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Dabigatran etexilate (DE) is a direct thrombin inhibitor, which has been approved for the treatment of non-valvular atrial fibrillation (AF), and for the prevention and treatment of venous thromboembolism (VTE). Despite large randomized clinical trials and independent observational studies providing robust data concerning DE safety and efficacy, some physicians still perceive mild-to-moderate renal impairment and old age as a relative contraindication to its use. In this article, we review the available scientific evidence supporting the use of DE in these clinical situations. Patients with AF and chronic kidney disease (CKD) are per se at high risk of stroke, bleeding and mortality. Although there is evidence of clinical benefit of anticoagulation in these patients, anticoagulant therapy requires caution and demands careful clinical monitoring, regardless of the drug used. In patients with no contraindication to its use, the clinical benefit of DE versus warfarin is independent of renal function. The elderly with AF are frequently undertreated because of the perception of high bleeding risk and limited clinical benefit. However, the clinical benefit of anticoagulation is independent of patient age, and age per se should not represent a contraindication to anticoagulation. DE has been extensively studied in the elderly, both in randomized clinical trials and in observational studies: DE 150 mg BID should not be used in patients 80 years of age or older, while DE 110 mg BID is as safe as warfarin. Intracranial haemorrhages reduction by DE compared with warfarin is preserved in the elderly. Therefore, mild and moderate CKD and being elderly should not deter physicians from prescribing DE. Furthermore, the availability of a specific antidote is expected to improve the safety of the use of DE in clinical practice.

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Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation

Cited by 99 publications

References 26 publications

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

Patients' Characteristics Affect the Survival Benefit of Warfarin Treatment for Hemodialysis Patients with Atrial Fibrillation. A Historical Cohort Study

Dabigatran etexilate: appropriate use in patients with chronic kidney disease and in the elderly patients

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