Warfarin Dosing and Outcomes in Chronic Kidney Disease: A Closer Look at Warfarin Disposition

2019 ◽  
Vol 20 (8) ◽  
pp. 633-645
Author(s):  
Osama Y. Alshogran

Background: Chronic Kidney Disease (CKD) is a prevalent worldwide health problem. Patients with CKD are more prone to developing cardiovascular complications such as atrial fibrillation and stroke. This warrants the use of oral anticoagulants, such as warfarin, in this population. While the efficacy and safety of warfarin in this setting remain controversial, a growing body of evidence emphasizes that warfarin use in CKD can be problematic. This review discusses 1) warfarin use, dosing and outcomes in CKD patients; and 2) possible pharmacokinetic mechanisms for altered warfarin dosing and response in CKD. Methods: Structured search and review of literature articles evaluating warfarin dosing and outcomes in CKD. Data and information about warfarin metabolism, transport, and pharmacokinetics in CKD were also analyzed and summarized. Results: The literature data suggest that changes in warfarin pharmacokinetics such as protein binding, nonrenal clearance, the disposition of warfarin metabolites may partially contribute to altered warfarin dosing and response in CKD. Conclusion: Although the evidence to support warfarin use in advanced CKD is still unclear, this synthesis of previous findings may help in improving optimized warfarin therapy in CKD settings.

2020 ◽  
Vol 16 (6) ◽  
pp. 1031-1038
Author(s):  
T. V. Pavlova

Anticoagulant therapy in elderly patients with atrial fibrillation and concomitant diseases is often the challenge for clinicians. The high risk of stroke is inherent in atrial fibrillation, and it increases when combined with coronary heart disease and chronic kidney disease. On the other hand, the comorbidity increases the risk of bleeding. Older age is also the risk factor of thrombotic and hemorrhagic complications. As a consequence, the choice of specific anticoagulant should be based on a solid evidences, obtained both from randomized clinical trials and from daily clinical practice. In the ROCKET AF trail the direct oral anticoagulant rivaroxaban showed a tendency to reduce the risk of thromboembolism by 20% compared with warfarin in the patients aged 75 years and older. The safety of rivaroxaban has been evaluated in the XANTUS POOLED program. According to the follow-up results for 12 months, more than 96% of patients didn't have any adverse event, and the number of patients with major bleeding was 1.5%. Several meta-analyzes reported a reduction of cardiovascular complications in patients treated by rivaroxaban. In the ROCKET AF trail, a “renal” dose of rivaroxaban (15 mg OD) was studied in patients with chronic kidney disease. The efficacy and safety of rivaroxaban were validated in this patients, and a simple algorithm for selecting the dose of this drug in patients with chronic kidney disease was provided. 


ESC CardioMed ◽  
2018 ◽  
pp. 2237-2240
Author(s):  
Ken Okumura ◽  
Hirofumi Tomita

Atrial fibrillation (AF) is one of the common cardiovascular complications in patients with chronic kidney disease (CKD), and enhances synergistically the risks of stroke, systemic thromboembolism, and bleeding complications, resulting in increased mortality. One major concern in the treatment strategy for patients with AF and CKD has been a lack of robust evidence that improves quality of life and prognosis. Although a paradigm shift from warfarin to non-vitamin K antagonist oral anticoagulants has occurred in stroke prevention in AF, the role and indication of non-vitamin K antagonist oral anticoagulants remain to be established in patients with advanced CKD. Considering the fact that the prevalence of CKD in the general population increases with age, elderly people suffering from both CKD and AF will be increasingly frequent in the highly aged societies.


2019 ◽  
Vol 42 (11) ◽  
pp. 1463-1470 ◽  
Author(s):  
Harpreet S. Bhatia ◽  
Joseph Bailey ◽  
Ozan Unlu ◽  
Katherine Hoffman ◽  
Robert J. Kim

2019 ◽  
Vol 132 (11) ◽  
pp. 1335-1343.e6 ◽  
Author(s):  
Shang-Hung Chang ◽  
Chien-Chia V. Wu ◽  
Yung-Hsin Yeh ◽  
Chang-Fu Kuo ◽  
Yu-Ling Chen ◽  
...  

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 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.


Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
Konark Malhotra ◽  
Muhammad F Ishfaq ◽  
Nitin Goyal ◽  
John Parissis ◽  
Anne Alexandrov ◽  
...  

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