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

2020 ◽  
Vol 10 (1) ◽  
pp. 83
Author(s):  
Michele Magnocavallo ◽  
Antonio Bellasi ◽  
Marco Valerio Mariani ◽  
Maria Fusaro ◽  
Maura Ravera ◽  
...  

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.

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 422
Author(s):  
Mihai Ciprian Stoica ◽  
Zsolt Gáll ◽  
Mirela Liana Gliga ◽  
Carmen Denise Căldăraru ◽  
Orsolya Székely

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.


Author(s):  
Cynthia A. Jackevicius ◽  
Lingyun Lu ◽  
Zunera Ghaznavi ◽  
Alberta L. Warner

Background: Patients with heart failure and atrial fibrillation are an important atrial fibrillation subgroup in which direct oral anticoagulants (DOACs) have not been adequately studied in real-world settings. Since DOACs rely on renal elimination and renal dysfunction is prevalent in patients with heart failure, their use may increase bleeding risk, negating some of their advantage over warfarin. Methods: We conducted a retrospective cohort study using linked Veterans Administration databases of patients with heart failure newly started on warfarin or DOACs for atrial fibrillation from October 2010 to August 2017 (23 635 warfarin, 25 823 DOAC). Outcomes included time to first bleeding, stroke, and death using Cox proportional hazards models with inverse probability of treatment weighting. Results: Total bleeding (hazard ratio, 0.62 [95% CI, 0.56–0.68]), major bleeding (hazard ratio, 0.49 [95% CI, 0.40–0.61]), and death (hazard ratio, 0.74 [95% CI, 0.71–0.78]) were lower with DOAC than warfarin, and with apixaban and dabigatran, but not rivaroxaban. Moderate/severe chronic kidney disease was common (48.7%); moderate chronic kidney disease was associated with increased bleeding with DOACs but not warfarin. However, death and bleeding remained lower with DOACs than warfarin across all renal function levels and clinical subgroups. A >20% transient/persistent decline in renal function occurred in 53% of DOAC-treated patients at some point during follow-up, would have required dose reduction in 10.5% of patients, and was associated with increased bleeding. Dose adjustments were made more often, and bleeding and death were lower in patients seen by pharmacists or anticoagulation clinics. There were significant between-site variations in DOAC dosing. Conclusions: DOACs overall, apixaban, and dabigatran, but not rivaroxaban, were associated with less total bleeding and death than warfarin in patients with heart failure and atrial fibrillation at all levels of renal function. Renal function decline resulted in increased bleeding in patients with DOACs. DOAC dose adjustment was often indicated, associated with increased bleeding when not adjusted, emphasizing the need for closer monitoring in these patients.


2019 ◽  
pp. 14-19
Author(s):  
I. S. Daabul ◽  
A. A. Sokolova ◽  
I. L. Tsarev ◽  
D. A. Napalkov ◽  
V. V. Fomin

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. 


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Emma Kirstine Laugesen ◽  
Laila Staerk ◽  
Nicholas Carlson ◽  
Anne-Lise Kamper ◽  
Jonas Bjerring Olesen ◽  
...  

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.


Heart ◽  
2020 ◽  
pp. heartjnl-2020-317923 ◽  
Author(s):  
Olivier Hanon ◽  
Jean-Sébastien Vidal ◽  
George Pisica-Donose ◽  
Galdric Orvoën ◽  
Jean-Philippe David ◽  
...  

ObjectiveDirect oral anticoagulants have been evaluated in the general population, but proper evidence for their safe use in the geriatric population is still missing. We compared the bleeding risk of a direct oral anticoagulant (rivaroxaban) and vitamin K antagonists (VKAs) among French geriatric patients with non-valvular atrial fibrillation (AF) aged ≥80 years.MethodsWe performed a sequential observational prospective cohort study, using data from 33 geriatric centres. The sample comprised 908 patients newly initiated on VKAs between September 2011 and September 2014 and 995 patients newly initiated on rivaroxaban between September 2014 and September 2017. Patients were followed up for up to 12 months. One-year risks of major, intracerebral, gastrointestinal bleedings, ischaemic stroke and all-cause mortality were compared between rivaroxaban-treated and VKA-treated patients with propensity score matching and Cox models.ResultsMajor bleeding risk was significantly lower in rivaroxaban-treated patients (7.4/100 patient-years) compared with VKA-treated patients (14.6/100 patient-years) after multivariate adjustment (HR 0.66; 95% CI 0.43 to 0.99) and in the propensity score–matched sample (HR 0.53; 95% CI 0.33 to 0.85). Intracerebral bleeding occurred less frequently in rivaroxaban-treated patients (1.3/100 patient-years) than in VKA-treated patients (4.0/100 patient-years), adjusted HR 0.59 (95% CI 0.24 to 1.44) and in the propensity score–matched sample HR 0.26 (95% CI 0.09 to 0.80). Major lower bleeding risk was largely driven by lower risk of intracerebral bleeding.ConclusionsOur study findings indicate that bleeding risk, largely driven by lower risk of intracerebral bleeding, is lower with rivaroxaban than with VKA in stroke prevention in patients ≥80 years old with non-valvular AF.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Pardo Sanz ◽  
L M Rincon ◽  
P Guedes Ramallo ◽  
L Belarte ◽  
G De Lara ◽  
...  

Abstract Aims Balance between embolic and bleeding risk is challenging in patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. We further evaluated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with cancer. Methods The AMBER-AF registry is an observational multicentre study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain. 1237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. Mean follow-up was 3.1 years. Results Both groups were similar in age, CHA2DS2-VASc and HASB-LED scores. Lack of guidelines recommended therapies was more frequent among patients with cancer. Compared with patients without cancer, adjusted rates of stroke (hazard ratio [95% confidence interval]) in cancer patients were higher (1.56 [1.04–2.35]), whereas bleeding rates remained similar (1.25 [0.95–1.64]). Within the group of patients with cancer, the use of DOACs vs VKAs did not entail differences in the adjusted rates of stroke (0.91 [0.42–1.99]) or severe bleedings (1.53 [0.93–2.53]). Follow-up events Conclusions Antithrombotic management of AF frequently differs in patients with breast cancer. While breast cancer is associated with a higher risk of incident stroke, bleeding events remained similar. Patients with cancer treated with DOACs experienced similar rates of stroke and bleeding as those with VKAs.


2016 ◽  
Vol 23 (1) ◽  
pp. 5-19 ◽  
Author(s):  
Zachary Stacy ◽  
Sara Richter

Atrial fibrillation (AF) is a significant risk factor for stroke and peripheral thromboembolic events (TEs). Preventing blood clots in the heart to reduce stroke and TE risk is a key goal of AF therapy. Traditional stroke risk assessment tools for patients with nonvalvular AF include the CHADS2 and CHA(2)DS(2)-VASc scores, while long-term outcome data with the newer direct oral anticoagulants (DOACs) are emerging. The goals of this review were to assess traditional therapies and existing treatment guidelines and to discuss key pharmacologic properties of the DOACS, noting how these may benefit at-risk patients with AF. This narrative review was developed on the basis of the authors’ clinical knowledge, extensive reading of the literature, and broad pharmacy experience in the management of patients with AF. Limitations of oral vitamin K antagonists (VKAs) include slow onset of action, the need for regular monitoring of their anticoagulation effect, significant food and drug interactions, and unpredictable dose–response properties. Key clinical trial data led to the approvals of apixaban, dabigatran etexilate, edoxaban, and rivaroxaban in the United States to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF. With predictable pharmacologic properties and limited drug and/or dietary interactions, the DOACs offer several benefits over traditional oral anticoagulation therapy with VKA. However, they have limitations, including the absence of immediate reversal agents and limited options for monitoring their anticoagulation effects in clinical practice. As experience with the use of DOACs grows, optimized treatment regimens and improved patient care are expected.


2021 ◽  
Vol 96 (4) ◽  
pp. 296-311
Author(s):  
Ki Hong Lee ◽  
Jin-Bae Kim ◽  
Seung Yong Shin ◽  
Boyoung Joung

Atrial fibrillation (AF) is a strong risk factor for ischemic stroke and systemic embolism. To prevent thromboembolic events in patients with AF, anticoagulation therapy is essential. The anticoagulant strategy is determined after stroke and bleeding risk assessments using the CHA2DS2-VASc and HAS-BLED scores, respectively; both consider clinical risk factors. Vitamin K antagonists (VKAs) are the sole anticoagulant option in AF patients with a prosthetic mechanical valve or moderate-severe mitral stenosis; in all other AF patients VKA or non-vitamin K antagonist oral anticoagulants are therapeutic options. However, antiplatelet therapy should not be used for stroke prevention in AF patients. Anticoagulation is not needed in AF patients with low stroke risk but strongly recommended in those with a with low bleeding risk. Left atrial appendage (LAA) occlusion offers an alternative in AF patients in whom long-term anticoagulation is contraindicated. Surgical occlusion or the exclusion of LAA can be considered for stroke prevention in AF patients undergoing cardiac surgery. In this article, we review existing data for stroke prevention and suggest optimal strategies to prevent stroke in AF patients.


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