Oral Anticoagulant Treatment in Patients with Atrial Fibrillation and Chronic Kidney Disease

Over the past few decades, a series of innovative medicines have been developed in order to optimize anticoagulation therapy for atrial fibrillation (AF). As a result, a number of nonvitamin K antagonist oral anticoagulants (NOAC) that directly target the enzymatic activity of factor II and factor Xa have been successfully licensed providing a more predictable effect and better safety profile compared to conventional anticoagulants (heparins and vitamin K antagonists (VKAs)). However, comparative efficacy and safety data is limited in patients with advanced chronic kidney disease (i.e., CKD stage 4/5 and end stage renal disease) because patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 were actively excluded from landmark trials, thus representing a major clinical limitation for the currently available agents. However, the renal function of AF patients can be altered over time. On the other hand, patients with CKD have an increased risk of developing AF. This review article will provide an overview of current concepts and recent evidence guiding the clinical use of NOACs in patients with CKD requiring chronic anticoagulation, and the associated risks and benefits of treatment in this specific patient population.

Download Full-text

Thromboembolic and Bleeding Risk in Atrial Fibrillation Patients with Chronic Kidney Disease: Role of Anticoagulation Therapy

Journal of Clinical Medicine ◽

10.3390/jcm10010083 ◽

2020 ◽

Vol 10 (1) ◽

pp. 83

Author(s):

Michele Magnocavallo ◽

Antonio Bellasi ◽

Marco Valerio Mariani ◽

Maria Fusaro ◽

Maura Ravera ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Bleeding Risk ◽

Therapeutic Window ◽

Hemorrhagic Risk

Atrial fibrillation (AF) and chronic kidney disease (CKD) are strictly related; several independent risk factors of AF are often frequent in CKD patients. AF prevalence is very common among these patients, ranging between 15% and 20% in advanced stages of CKD. Moreover, the results of several studies showed that AF patients with end stage renal disease (ESRD) have a higher mortality rate than patients with preserved renal function due to an increased incidence of stroke and an unpredicted elevated hemorrhagic risk. Direct oral anticoagulants (DOACs) are currently contraindicated in patients with ESRD and vitamin K antagonists (VKAs), remaining the only drugs allowed, although they show numerous critical issues such as a narrow therapeutic window, increased tissue calcification and an unfavorable risk/benefit ratio with low stroke prevention effect and augmented risk of major bleeding. The purpose of this review is to shed light on the applications of DOAC therapy in CKD patients, especially in ESRD patients.

Download Full-text

Non-vitamin K antagonist oral anticoagulants vs. vitamin-K antagonists in patients with atrial fibrillation and chronic kidney disease: a nationwide cohort study

Thrombosis Journal ◽

10.1186/s12959-019-0211-y ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Emma Kirstine Laugesen ◽

Laila Staerk ◽

Nicholas Carlson ◽

Anne-Lise Kamper ◽

Jonas Bjerring Olesen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

All Cause Mortality ◽

Comparable Population

Abstract Background We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. Methods By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011–2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. Results Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26–0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39–1.78), MI (HR: 0.45, 95% CI: 0.18–1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77–1.26). Conclusion NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.

Download Full-text

Risk of Stroke, Bleeding, and Death in Patients with Nonvalvular Atrial Fibrillation and Chronic Kidney Disease

Cardiology ◽

10.1159/000504877 ◽

2020 ◽

Vol 145 (3) ◽

pp. 178-186

Author(s):

Yoav Arnson ◽

Moshe Hoshen ◽

Adi Berliner-Sendrey ◽

Orna Reges ◽

Ran Balicer ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Impaired Renal Function ◽

Bleeding Risk ◽

Intracranial Bleeding ◽

Increased Risk ◽

Ckd Stage ◽

Stroke Death

Introduction: Atrial fibrillation (AF) and chronic kidney disease (CKD) are both associated with increased risk of stroke, and CKD carries a higher bleeding risk. Oral anticoagulation (OAC) treatment is used to reduce the risk of stroke in patients with nonvalvular AF (NVAF); however, the risk versus benefit of OAC for advanced CKD is continuously debated. We aim to assess the management and outcomes of NVAF patients with impaired renal function within a population-based cohort. Methods: We conducted a retrospective observational cohort study using ICD-9 healthcare coding. Patients with incident NVAF between 2004 and 2015 were identified stratified by CKD stage. We compared treatment strategies and estimated risks of stroke, death, or any major bleeding based on CKD stages and OAC treatment. Results: We identified 85,116 patients with incident NVAF. Patients with impaired renal function were older and had more comorbidities. OAC was most common among stage 2 CKD patients (49%) and least in stages 4–5 CKD patients (27.6%). Higher CKD stages were associated with worse outcomes. Stroke rates increased from 1.04 events per 100 person-years (PY) in stage 1 CKD to 3.72 in stages 4–5 CKD. Mortality increased from 3.42 to 32.95 events/100 PY, and bleeding rates increased from 0.89 to 4.91 events/100 PY. OAC was associated with reduced stroke and intracranial bleeding risk regardless of CKD stage, and with a reduced mortality risk in stages 1–3 CKD. Conclusion: Among NVAF patients, advanced renal failure is associated with higher risk of stroke, death, and bleeding. OAC was associated with reduced stroke and intracranial bleeding risk, and with improved survival in stages 1–3 CKD.

Download Full-text

Oral Factor Xa Inhibitors versus Warfarin for the Treatment of Venous Thromboembolism in Advanced Chronic Kidney Disease

Advances in Hematology ◽

10.1155/2021/8870015 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Tania Ahuja ◽

Kelly Sessa ◽

Cristian Merchan ◽

John Papadopoulos ◽

David Green

Keyword(s):

Chronic Kidney Disease ◽

Venous Thromboembolism ◽

Kidney Disease ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Safety Data ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

Advanced Chronic Kidney Disease ◽

Ckd Stage

Introduction. Warfarin remains the preferred oral anticoagulant for the treatment of venous thromboembolism (VTE) in patients with advanced chronic kidney disease (CKD). Although the direct oral anticoagulants (DOACs) have become preferred for treatment of VTE in the general population, patients with advanced CKD were excluded from the landmark trials. Postmarketing, safety data have demonstrated oral factor Xa inhibitors (OFXais) such as apixaban and rivaroxaban to be alternatives to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, it remains unknown if these safety data can be extrapolated to the treatment of VTE and CKD. Methods. A retrospective cohort study from January 2013 to October 2019 was performed at NYU Langone Health. All adult patients with CKD stage 4 or greater, treated with anticoagulation for VTE, were screened. The primary outcome was tolerability of anticoagulant therapy at 3 months, defined as a composite of bleeding, thromboembolic events, and/or discontinuation rates. The secondary outcomes included bleeding, discontinuations, and recurrent thromboembolism. Results. There were 56 patients evaluated, of which 39 (70%) received warfarin and 17 (30%) received an OFXai (apixaban or rivaroxaban). Tolerability at 3 months was assessed in 48/56 patients (86%). A total of 34/48 (71%) patients tolerated anticoagulation at 3 months, 12 (80%) in the OFXai arm, and 22 (67%) in the warfarin arm ( p = 0.498 ). There were 10/48 (21%) patients that experienced any bleeding events within 3 months, 7 on warfarin, and 3 on apixaban. Recurrence of thromboembolism within 3 months occurred in 3 patients on warfarin, with no recurrence in the OFXai arm. Discussion. OFXais were better tolerated compared to warfarin for the treatment of VTE in CKD, with lower rates of bleeding, discontinuations, and recurrent thromboembolism in a small cohort. Future prospective studies are necessary to confirm these findings.

Download Full-text

Atrial Fibrillation and Malignancy: The Clinical Performance of Non–Vitamin K Oral Anticoagulants—A Systematic Review

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0038-1661386 ◽

2018 ◽

Vol 45 (02) ◽

pp. 205-214 ◽

Cited By ~ 11

Author(s):

Roberta Bottino ◽

Anna Rago ◽

Pierpaolo Micco ◽

Antonio D' Onofrio ◽

Biagio Liccardo ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Vitamin K ◽

Clinical Performance ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Therapeutic Anticoagulation ◽

Increased Risk ◽

Active Cancer

AbstractAtrial fibrillation (AF) is commonly diagnosed in the setting of active cancer. Because of an increased risk of either thromboembolic events or bleeding, the decision to initiate therapeutic anticoagulation in patients with active cancer can be challenging. Moreover, little is still known about the optimal anticoagulation therapy in the setting of AF and cancer, and no guidelines are as yet available. Considering that nonvitamin K antagonist oral anticoagulants (NOACs) are recommended as alternatives to vitamin K antagonists for stroke prevention in AF patients with CHA2DS2-VASc score ≥2, the authors performed a systematic review of the current literature to describe the efficacy and safety of NOACs in AF patients with malignancy.

Download Full-text

Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Renal Dysfunction

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2021-02-03 ◽

2021 ◽

Vol 17 (1) ◽

pp. 62-72

Author(s):

Z. D. Kobalava ◽

A. A. Shavarov ◽

M. V. Vatsik-Gorodetskaya

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Renal Dysfunction ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Disease Epidemiology ◽

Increased Risk ◽

Estimate Glomerular Filtration Rate

Atrial fibrillation and renal dysfunction often coexist, each disorder may predispose to the other and contribute to worsening prognosis. Both atrial fibrillation and chronic kidney disease are associated with increased risk of stroke and thromboembolic complications. Oral anticoagulation for stroke prevention is therefore recommended in patients with atrial fibrillation and decreased renal function. Each direct oral anticoagulant has unique pharmacologic properties of which clinician should be aware to optimally manage patients. The doses of direct oral anticoagulants require adjustment for renal function. There is debate regarding which equation, the Chronic Kidney Disease Epidemiology (CKD-EPI) equation vs. the Cockcroft-Gault equation, should be used to estimate glomerular filtration rate in patients with atrial fibrillation treated with direct oral anticoagulants. Our review tries to find arguments for benefit of direct oral anticoagulants in patients with renal dysfunction.

Download Full-text

Abstract 13927: Advanced Age and Preferential Use of Vitamin K Antagonists in Severe Renal Impairment: First Results of the XARENO Registry in Patients With Non-valvular Atrial Fibrillation and Non-dialysis Dependent Advanced Chronic Kidney Disease

Circulation ◽

10.1161/circ.142.suppl_3.13927 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Reinhold Kreutz ◽

Gilbert Deray ◽

Juergen Floege ◽

Marianne Gwechenberger ◽

Andreas Luft ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Vitamin K ◽

Severe Renal Impairment ◽

Vitamin K Antagonists ◽

Thromboembolic Events ◽

Increased Risk ◽

First Results

Introduction: Patients with chronic kidney disease (CKD) and non-valvular atrial fibrillation (NVAF) are at increased risk for both ischemic stroke and hemorrhage. In addition, treatment with vitamin K antagonists (VKA) has been associated with worsening of renal function compared to direct oral anticoagulants (DOACs). XARENO (Factor XA -inhibition in RENal patients with non-valvular atrial fibrillation Observational registry) is an ongoing prospective, non-interventional, observational study conducted in Europe. XARENO evaluates the effectiveness of rivaroxaban in preserving renal function and preventing thromboembolic events as compared to VKA in NVAF patients with CKD in clinical practice. Methods: XARENO included male and female NVAF patients ≥18 years old with an estimated glomerular filtration rate (eGFR) between 15 and 49 mL/min per 1.73 m 2 and an indication for anticoagulation. Enrolment took place from April 2016 until January 2020. Patients treated with either rivaroxaban or VKA were included, while patients in whom physicians were withholding any anticoagulation could be also enrolled. Minimal planned follow-up is one year. Primary observational outcomes include efficacy and safety outcomes (progression of CKD, stroke, other thromboembolic events, major cardiovascular events, major bleeding, and all-cause mortality). First results on outcomes in the full cohort are expected in 2021. Results: In this analysis of a first set of 1485 patients (56.1% males), 731 and 666 patients received rivaroxaban and VKA, while 88 patients did not receive any anticoagulation. Mean age at baseline was 77.3 years (67.5% older than 75 years) with a mean eGFR of 38.9 mL/min per 1.73 m 2 . Overall 74.7% of patients had eGFR values below 45 mL/min per 1.73 m 2 and 28.0% below 30 mL/min per 1.73 m 2 . In the latter group, use of a VKA was about twofold more frequent compared to rivaroxaban. Conclusions: This first analysis of XARENO patients reveals the very high age of NVAF patients with concomitant non-dialysis dependent advanced CKD and a preferential use of VKA in stage 4 CKD. XARENO aims to provide important information on the real-world effectiveness and safety of rivaroxaban compared with VKA for this vulnerable patient group.

Download Full-text

Safety of Using Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Chronic Kidney Disease

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2019-15-4-530-537 ◽

2019 ◽

Vol 15 (4) ◽

pp. 530-537 ◽

Cited By ~ 1

Author(s):

V. I. Petrov ◽

O. V. Shatalova ◽

A. S. Gerasimenko ◽

V. S. Gorbatenko

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Renal Pathology ◽

Rapid Progression ◽

Thromboembolic Complications ◽

Randomized Studies ◽

Increased Risk

The purpose of this review is to examine the possibilities and prospects for the use of direct oral anticoagulants for the prevention of thromboembolic complications in patients with atrial fibrillation and chronic kidney disease. Chronic kidney disease is an independent risk factor for cardiovascular complications. Atrial fibrillation is associated with a higher risk of developing chronic kidney disease and more rapid progression of existing renal pathology. The presence of chronic kidney disease in atrial fibrillation on the one hand leads to an increased risk of thromboembolism, and on the other to an increased risk of bleeding when using anticoagulants. The standard for the prevention of thromboembolic complications in atrial fibrillation, including those with concomitant renal pathology, was considered warfarin for many years. However, modern studies have shown that the use of warfarin may enhance vascular calcification in patients with chronic kidney disease, which in turn may lead to an increased risk of ischemic strokes.Analyzing clinical recommendations, randomized studies, meta-analyzes and a systematic review on the use of anticoagulants in patients with atrial fibrillation and renal pathology, revealed the advantage of using direct oral anticoagulants over warfarin at stage 1-3 of chronic kidney disease. Data on the use of direct oral anticoagulants with a more pronounced renal dysfunction and in patients on dialysis is limited due to the lack of a sufficient number of large randomized studies. Due to the presence of renal clearance in all oral anticoagulants, their pharmacokinetics changes to some extent with a decrease in the glomerular filtration rate, which requires dose adjustment of drugs depending on creatinine clearance. Therefore, the use of anticoagulants for the prevention of thromboembolic complications during atrial fibrillation requires special attention in patients with chronic kidney disease.

Download Full-text

MO123USE OF RIVAROXABAN VERSUS WARFARIN IN PATIENTS WITH ATRIAL FIBRILLATION AND ADVANCED CHRONIC KIDNEY DISEASE*

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab092.001 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Sherzod Abdullaev ◽

Rano Igamberdieva ◽

Olimkhon Sharapov

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Oral Anticoagulants ◽

Randomized Study ◽

Academic Research ◽

Minor Bleeding ◽

Stage 4 ◽

Ckd Stage ◽

Clinically Significant

Abstract Background and Aims Patients with chronic kidney disease (CKD) develop bleeding and thromboembolic tendencies, so the indication for the use of anticoagulants for atrial fibrillation (AF) is difficult. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are the main complications. In recent years, new oral anticoagulants (rivaroxaban) have been developed and have shown superiority over classic anti-vitamin K anticoagulants in preventing the risk of stroke, systemic embolism and bleeding. Aim is to evaluate the safety parameters of rivaroxaban in patients with stage 4 chronic kidney disease (CKD) or a transient sustained decrease in glomerular filtration rate (GFR) to 15–29 ml/min/1,73 m2 in the presence of atrial fibrillation (AF). Method Multicenter prospective randomized study that included patients from cardiology departments in 2019. Of 5448 hospitalized patients, 109 (2%) patients with AF and CKD stage 4 or a sustained decrease in GFR to 15-29 ml/min/1.73 m2 were randomized in a 2:1 ratio to rivaroxaban 15 mg/day (n=73) or warfarin (n=36). Primary endpoint: development of large, small and small clinically significant bleeding according to the BARC (Bleeding Academic Research Consortium) and ISTH (International Society on Thrombosis and Hemostasis) scales. The average follow-up period is 12 months. Results Patients taking warfarin were significantly more likely to develop minor bleeding according to BARC scales (n=26 (72.2%) versus n=31 (42.4%), p<0.01) and ISTH (n=22 (61.1%) versus n=27 (36.9%), p<0.01) and all clinically significant (minor clinically significant and major) bleeding according to the ISTH scale [n=10 (27.7%) versus n=8 (10.9%), p=0.03]. The number of readmissions was 32 (43.8% of patients) in the rivaroxaban group, 17 (47.2% of patients) in the warfarin group (p=0.57), of which 12 (37.5%) and 7 (41.1%) (in the rivaroxaban and warfarin groups, respectively) - for urgent reasons (p=0.96). A significant improvement in the dynamics of creatinine levels, GFR (according to CKD-EPI) in the rivaroxaban group was revealed. Conclusion The study provides evidence of a favorable safety profile for rivaroxaban compared with warfarin in patients with AF and advanced CKD.

Download Full-text

Anticoagulant therapy in patients with atrial fibrillation and concomitant chronic kidney disease: the results of a prospective study

Medical Council ◽

10.21518/2079-701x-2019-5-14-19 ◽

2019 ◽

pp. 14-19

Author(s):

I. S. Daabul ◽

A. A. Sokolova ◽

I. L. Tsarev ◽

D. A. Napalkov ◽

V. V. Fomin

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Kidney Function ◽

Anticoagulant Therapy ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Thromboembolic Complications ◽

Hemorrhagic Events

In recent years, both Russian and foreign authors have published many papers on anticoagulant therapy for atrial fibrillation (AF). The largest are devoted to the study of direct oral anticoagulants (DOACs), which have appeared in this field since 2009, and their comparison with vitamin K antagonists (VKAs) in terms of efficacy, safety and other important characteristics. There are far fewer studies on DOACs and their comparison with VKAs and with each other in patients with AF and reduced kidney function. Most of them are retrospective. Meanwhile, the prevalence of chronic kidney disease (CKD) in the population is very high, and doctors are faced with a problem of selecting anticoagulant therapy for these patients.Purpose. To assess the effect of VKAs and DOACs on renal function in real clinical practice in patients with AF depending on the stage of CKD.Materials and methods. A prospective single-centre non-randomized non-interventional observational study in parallel groups was conducted. The study included 92 patients with AF and CKD of 1-4 stages (S1-S4). The comparison group consisted of 35 patients with AF without concomitant CKD. The patients’ age ranged from 44 to 94 years (mean age was 72.2 ± 8.5 years). Patients of both groups received anticoagulant therapy with VKA (warfarin) or one of the registered in the Russian Federation DOACs (dabigatran, rivaroxaban, apixaban). During the observation (median was 10 months), follow-up visits were every 3 months. On visits we conducted the evaluation of effectiveness (strokes / TIA and thromboembolic complications) and safety (major and minor hemorrhagic events) of anticoagulant therapy, as well as the dynamics of kidney function (CC by Cockroft-Gault, GFR by CKD-EPI).Results. The main results are devoted to patients with AF and concomitant CKD. Significant dynamics of the kidney function depending on the anticoagulant taken (VKA or representatives of the DOACs class) were not identified. There were not any thromboembolic complications and major bleedings during the observation period. Statistically significant more minor bleedings on any dose of rivaroxaban in comparison with other anticoagulants were identified.Conclusions. In patients with AF and CKD, there was no significant effect of one or another anticoagulant on the kidney function, which is probably related to the concomitant nephroprotective therapy obtained in a large percentage of cases (ACE inhibitors / ARA, calcium antagonists, statins). Therapy with DOACs and warfarin in patients with AF and CKD for an average of 10 months of followup was effective and safe. In case of AF and CKD combination, the use of dabigatran or apixaban seems to be more preferable in relation to minor bleedings, the use of which less often leads to the development of hemorrhagic events.

Download Full-text