scholarly journals The Nephrological Aspects of the Use of Rivaroxaban and Other Direct Peroral Anticoagulants in Non-Valvular Atrial Fibrillation

Kardiologiia ◽  
2019 ◽  
Vol 59 (6) ◽  
pp. 60-69
Author(s):  
M. M. Batiushin

Chronic kidney disease (CKD) is a powerful cardiovascular risk factor, its presence is accompanied by an increased risk of hospitalization for exacerbation of chronic heart failure (CHF), adverse outcomes in myocardial infarction, and cardiovascular mortality. Among the adverse events, an increased risk of atrial fibrillation (AF) should be noted. This article contains discussion of current approaches to the treatment of AF in patients with different stages of CKD, data on benefits of certain direct oral anticoagulants, as well as comparative characteristics of therapy with direct oral anticoagulants and warfarin. Pharmacokinetics and pharmacodynamics of direct oral anticoagulants, which determine the features of therapy in CKD, are also considered.

Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001726
Author(s):  
Anthony P Carnicelli ◽  
Ruth Owen ◽  
Stuart J Pocock ◽  
David B Brieger ◽  
Satoshi Yasuda ◽  
...  

ObjectiveAtrial fibrillation (AF) and myocardial infarction (MI) are commonly comorbid and associated with adverse outcomes. Little is known about the impact of AF on quality of life and outcomes post-MI. We compared characteristics, quality of life and clinical outcomes in stable patients post-MI with/without AF.Methods/resultsThe prospective, international, observational TIGRIS (long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease) registry included 8406 patients aged ≥50 years with ≥1 atherothrombotic risk factor who were 1–3 years post-MI. Patient characteristics were summarised by history of AF. Quality of life was assessed at baseline using EQ-5D. Clinical outcomes over 2 years of follow-up were compared. History of AF was present in 702/8277 (8.5%) registry patients and incident AF was diagnosed in 244/7575 (3.2%) over 2 years. Those with AF were older and had more comorbidities than those without AF. After multivariable adjustment, patients with AF had lower self-reported quality-of-life scores (EQ-5D UK-weighted index, visual analogue scale, usual activities and pain/discomfort) than those without AF. CHA2DS2-VASc score ≥2 was present in 686/702 (97.7%) patients with AF, although only 348/702 (49.6%) were on oral anticoagulants at enrolment. Patients with AF had higher rates of all-cause hospitalisation (adjusted rate ratio 1.25 [1.06–1.46], p=0.008) over 2 years than those without AF, but similar rates of mortality.ConclusionsIn stable patients post-MI, those with AF were commonly undertreated with oral anticoagulants, had poorer quality of life and had increased risk of clinical outcomes than those without AF.Trial registration numberClinicalTrials: NCT01866904.


2021 ◽  
Vol 17 (1) ◽  
pp. 62-72
Author(s):  
Z. D. Kobalava ◽  
A. A. Shavarov ◽  
M. V. Vatsik-Gorodetskaya

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.


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 ◽  
Vol 15 (4) ◽  
pp. 530-537 ◽  
Author(s):  
V. I. Petrov ◽  
O. V. Shatalova ◽  
A. S. Gerasimenko ◽  
V. S. Gorbatenko

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.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Pastori ◽  
P Pignatelli ◽  
F Violi ◽  
G.Y.H Lip

Abstract Background The integrated management of atrial fibrillation (AF) patients according to the Atrial fibrillation Better Care (ABC, A, Avoid stroke with anticoagulation; B, better symptom management; C, Cardiovascular and comorbidity risk management) pathway has associated with a reduced incidence of thromboembolic events and mortality. However, whether this approach also results in a lower rate of cardiac complications is unknown. Purpose To investigate the rate of major adverse cardiovascular events (MACE) in AF patients according to compliance with the ABC pathway. Methods This prospective single-center cohort study included 1157 patients with nonvalvular AF from the ATHERO-AF study. The A, B, and C groups were defined as follows: “A” by a Time in Therapeutic Range ≥70% in vitamin K antagonists-treated patients or appropriate dose for patients on direct oral anticoagulants; “B” by a European Heart Rhythm Association (EHRA) symptom scale I-II (vs. III-IV), and “C” as optimized cardiovascular comorbidity management (i.e. use of ACE inhibitors in heart failure patients, blood pressure <140/90, use of statins and beta blockers in patients with prior ischemic heart disease). The primary end point was a composite of MACE including fatal/non-fatal myocardial infarction, coronary revascularization and cardiovascular death (progressive heart failure, sudden cardiac death and procedure-related death). Results Overall, 458 (39.6%) patients were optimally managed according to the ABC (ABC-compliant group), while the remaining 729 patients presented at least one uncontrolled component (ABC non-compliant group). During a mean follow up of 35 months, (2688 patient-years), 64 MACE were recorded 2.38%/year. Kaplan Meier curve analysis showed a significant higher rate of MACE in ABC non-compliant group compared to the ABC-compliant (54 and 10 MACE in each group, respectively, log-rank test p=0.006, figure). The risk of MACE increased by the number of uncontrolled ABC components: Hazard ratio HR) for 1 component 1.697, 95% Confidence Interval 95% CI 0.814–3.537, p=0.158; HR for 2 components 4.157, 95% CI 1.994–8.665, p<0.001); HR for 3 components 5.100, 95% CI 1.596–16.295, p=0.006. ABC non-compliant group remained associated with an increased risk of MACE using Cox proportional hazard regression analysis (HR 2.175, 95% CI 1.098–4.309, p=0.026) after adjustment for CHA2DS2VASc score, antiplatelet drugs and digoxin use. Conclusion The majority of AF patients is not currently optimally managed. An integrated care ABC approach is associated with a reduced risk of MACE in the AF population. Figure 1. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Hamatani ◽  
M Iguchi ◽  
Y Aono ◽  
K Ishigami ◽  
S Ikeda ◽  
...  

Abstract Background Atrial fibrillation (AF) increases the risk of death, stroke/systemic embolism and heart failure (HF). Plasma natriuretic peptide (NP) level is an important prognostic marker in HF patients. However, little is known regarding the prognostic significance of plasma NP level in AF patients without HF. Purpose The aim of this study is to investigate the relationship between plasma NP level and clinical outcomes such as all-cause death, stroke/systemic embolism and HF hospitalization during follow-up period in AF patients without HF. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in our city. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011, and follow-up data were available for 4,466 patients by the end of November 2019. From the registry, we excluded 1,220 patients without a pre-existing HF (defined as having one of the following; prior hospitalization for HF, New York Heart Association class ≥2, or left ventricular ejection fraction <40%). Among 3,246 AF patients without HF, we investigated 1,189 patients with the data of plasma BNP (n=401) or N-terminal pro-BNP (n=788) level at the enrollment. We divided the patients according to the quartile of each plasma BNP or NT-pro BNP level and compared the backgrounds and outcomes between these 4 groups stratified by plasma NP level. Results Of 1,189 patients, the mean age was 72.1±10.2 years, 454 (38%) were female and 684 (58%) were paroxysmal AF. The mean CHADS2 and CHA2DS2-VASc score were 1.6±1.1 and 2.9±1.5, respectively. Oral anticoagulants were prescribed in 671 (56%) at baseline. The median (interquartile range) BNP and N-terminal pro-BNP level were 84 (38, 176) and 500 (155, 984) pg/ml, respectively. Patients with high plasma NP level were older, and demonstrated lower prevalence of paroxysmal AF, higher CHADS2 and CHA2DS2-VASc scores and higher prevalence of chronic kidney disease and oral anticoagulants prescription (all P<0.01). A total of 165 all-cause death, 114 stroke/systemic embolism and 103 HF hospitalization occurred during the median follow-up period of 5.0 years. Kaplan-Meier curves demonstrated that higher plasma NP level was significantly associated with the incidences of all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF (Figure 1A). Multivariable Cox regression analysis revealed that plasma NP level could stratify the risk of clinical outcomes even after adjustment by type of AF, CHA2DS2-VASc score, chronic kidney disease and oral anticoagulant prescription (Figure 1B). Conclusion Plasma NP level is a significant prognostic marker for all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF, suggesting the importance of measuring plasma NP level in AF patients even without HF. Figure 1 Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Denas ◽  
G Costa ◽  
E Ferroni ◽  
N Gennaro ◽  
U Fedeli ◽  
...  

Abstract Introduction Anticoagulation therapy is central for the management of stroke in patients with non-valvular atrial fibrillation (NVAF). Persistence with oral anticoagulation is essential to prevent thromboembolic complications. Purpose To assess persistence levels of DOACs and look for possible predictors of treatment discontinuity in NVAF patients. Methods We performed a population-based retrospective cohort study in the Veneto Region (north-eastern Italy, about 5 million inhabitants) using the regional health system databases. Naïve patients initiating direct oral anticoagulants (DOACs) for stroke prevention in NVAF from July 2013 to September 2017 were included in the study. Patients were identified using Anatomical Therapeutic Chemical (ATC) codes, excluding other indications for anticoagulation therapy using ICD-9CM codes. Treatment persistence was defined as the time from initiation to discontinuation of the therapy. Baseline characteristics and comorbidities associated to the persistence of therapy with DOACs were explored by means of Kaplan-Meier curves and assessed through Cox regression. Results Overall, 17920 patients initiated anticoagulation with DOACs in the study period. Most patients were older than 74 years old, while gender was almost equally represented. Comorbidities included hypertension (72%), diabetes mellitus (17%), congestive heart failure (9%), previous stroke/TIA (20%), and prior myocardial infarction (2%). After one year, the persistence to anticoagulation treatment was 82.7%, while the persistence to DOAC treatment was 72.9% with about 10% of the discontinuations being due to switch to VKAs. On multivariate analysis, factors negatively affecting persistence were female gender, younger age (<65 years), renal disease and history of bleeding. Conversely, persistence was better in patients with hypertension, previous cerebral ischemic events, and previous acute myocardial infarction. Persistence to DOAC therapy Conclusion This real-world data show that within 12 months, one out of four anticoagulation-naïve patients stop DOACs, while one out of five patients stop anticoagulation. Efforts should be made to correct modifiable predictors and intensify patient education.


Author(s):  
Kyle P Hornsby ◽  
Kensey Gosch ◽  
Amy L Miller ◽  
Jonathan P Piccini ◽  
Renato D Lopes ◽  
...  

Background: Little data are available regarding differences in prognosis and health status between new-onset and prior atrial fibrillation (AF) among patients with acute myocardial infarction (AMI). Methods: The TRIUMPH study enrolled 4340 AMI patients who received longitudinal follow-up including SF-12 health status assessments through 1 year post-AMI. We compared 1-year mortality, rehospitalization, and functional status according to AF type (none, prior, new) after adjusting for differences in baseline characteristics. Results: A total of 212 AMI patients (4.9%) had prior AF and 254 (5.9%) had new-onset AF. Compared with no AF, new AF was associated with older age, male sex, first MI, worse baseline physical function, home atrioventricular nodal blocker use, and worse ventricular function (c-index 0.77). Rates of 1-year mortality were 6.2%, 14.5%, and 13.0%, and 1-year rehospitalization rates were 29.1%, 44.2%, and 36.8% for no, prior, and new AF, respectively. After multivariable adjustment, neither prior nor new AF was associated with increased 1-year mortality, and only prior AF was associated with increased risk of 1-year rehospitalization (Figure). After adjusting for baseline SF-12 physical function scores, patients with prior AF had lower 1-year scores than those with no AF (40.6 vs. 43.7, p <0.003), whereas patients with new AF had similar scores (42.9 vs. 43.7, p=0.36). Conclusion: New-onset AF during AMI is associated with a number of comorbidities but, unlike prior AF, is not associated with adverse outcomes. These results raise the question of whether AF is itself a cause of or simply a marker of comorbidities leading to downstream adverse outcomes after AMI.


2018 ◽  
Vol 118 (12) ◽  
pp. 2162-2170 ◽  
Author(s):  
Kamilla Steensig ◽  
Kevin Olesen ◽  
Troels Thim ◽  
Jens Nielsen ◽  
Svend Jensen ◽  
...  

Background Patients with atrial fibrillation (AF) have an increased risk of ischaemic stroke. The risk can be predicted by the CHA2DS2-VASc score, in which the vascular component refers to previous myocardial infarction, peripheral artery disease and aortic plaque, whereas coronary artery disease (CAD) is not included. Objectives This article explores whether CAD per se or extent provides independent prognostic information of future stroke among patients with AF. Materials and Methods Consecutive patients with AF and coronary angiography performed between 2004 and 2012 were included. The endpoint was a composite of ischaemic stroke, transient ischaemic attack and systemic embolism. The risk of ischaemic events was estimated according to the presence and extent of CAD. Incidence rate ratios (IRR) were calculated in reference to patients without CAD and adjusted for parameters included in the CHA2DS2-VASc score and treatment with anti-platelet agents and/or oral anticoagulants. Results Of 96,430 patients undergoing coronary angiography, 12,690 had AF. Among patients with AF, 7,533 (59.4%) had CAD. Mean follow-up was 3 years. While presence of CAD was an independent risk factor for the composite endpoint (adjusted IRR, 1.25; 1.06–1.47), extent of CAD defined as 1-, 2-, 3- or diffuse vessel disease did not add additional independent risk information. Conclusion Presence, but not extent, of CAD was an independent risk factor of the composite thromboembolic endpoint beyond the components already included in the CHA2DS2-VASc score. Consequently, we suggest that significant angiographically proven CAD should be included in the vascular disease criterion in the CHA2DS2-VASc score.


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