warfarin and Renal-Insufficiency--Chronic

Anticoagulant-related nephropathy (ARN) is a novel and not well-studied cause of acute kidney injury (AKI). The prevalence of ARN varies significantly between studies and is estimated at 20% in patients treated with warfarin. Patients with ARN have a significantly higher mortality risk and an increased risk of chronic kidney disease (CKD). Unexplained AKI with hematuria are clinical manifestations of ARN. In most cases, ARN is diagnosed within the first 2 months of anticoagulant therapy, but later ARN occurrence is possible. Among the studied anticoagulants, most data concern warfarin toxicity, whereas cases of ARN caused by direct oral anticoagulants (DOACs) have also been presented. Tubular obstruction by red blood cell casts or hemoglobin and iron tubular toxicity are the postulated mechanisms of ARN. On the molecular level, the inhibition of thrombin and protease-activated receptor-1 (PAR-1), leading to endothelial susceptibility to damage or abnormal protein C endothelial signaling, is suggested to contribute to ARN. Older age, impaired kidney function, hypertension, and diabetes mellitus are the main risk factors for ARN, but their significance may differ between anticoagulants. From therapeutic options, the withdrawal of the anticoagulant and the administration of its antidote, as well as corticosteroids or N-acetylcysteine, are proposed. Since the number of patients with kidney diseases on anticoagulants increases, and DOACs are starting to be more useful in this group of patients, we aim to summarize the pathogenesis, clinical picture and possible ways of treatment of DOAC-induced ARN.

Topics: Acute Kidney Injury; Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Renal Insufficiency, Chronic; Rivaroxaban; Warfarin

The frequent coexistence in daily clinical practice of chronic kidney disease (CKD) and atrial fibrillation (AF), especially in the elderly, represents a conundrum for physicians, mainly related to the management of anticoagulant therapy. The reduction of estimated glomerular filtration rate (eGFR) impairs anticoagulant clearance, increasing bleeding propensity. Moreover, dysfunctional responses of endothelial cells and inflammatory systems both trigger thromboembolic status. Those mechanisms pose an increased risk of adverse events for AF patients with CKD. While several data suggested the use of direct oral anticoagulants (DOACs) over warfarin as preferred anticoagulant strategy in patients with Stage 3A to Stage 4 CKD (eGFR range of 15-49 mL/min/1.73 m2), less is known about the optimal anticoagulation management in patients with end-stage renal disease (ESRD) or on renal replacement therapy (RRT). Furthermore, a pivotal feature to be considered when choosing the anticoagulant drug in CKD patients is represented by nephroprotective capability. Indeed, anticoagulant therapy with warfarin showed detrimental effects on kidney function, whereas DOACs demonstrated a beneficial effect on renal function preservation. Mounting data showed that, when pharmacological treatment cannot be pursued due to contraindication to anticoagulation, left atrial appendage occlusion (LAAO) may represent a valid alternative. This brief review outlines the current knowledge regarding anticoagulation therapy in ESRD/RRT patients, reporting new lines of evidence on the nephroprotective effect of oral anticoagulants and on the use of LAAO as a non-pharmacological alternative to oral anticoagulation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Endothelial Cells; Humans; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Stroke; Warfarin

Patients with chronic kidney disease (CKD) have an increased risk of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulants have not been studied in randomised controlled trials with CrCl < 30 ml/min. The objective of this review was to identify the impact of different anticoagulant strategies in patients with advanced CKD including dialysis.. We conducted a systematic review of randomized controlled trials and cohort studies, searching electronic databases from 1946 to 2022. Studies that evaluated both thrombotic and bleeding outcomes with anticoagulant use in CrCl < 50 ml/min were included.. Our initial search yielded 14,503 papers with 53 suitable for inclusion. RCTs comparing direct oral anticoagulants (DOACs) versus warfarin for patients with VTE and CrCl 30-50 ml/min found no difference in recurrent VTE events (RR 0.68(95% CI 0.42-1.11)) with reduced bleeding (RR 0.65 (95% CI 0.45-0.94)). Observational data in haemodialysis suggest lower risk of recurrent VTE and major bleeding with apixaban versus warfarin. Very few studies examining outcomes were available for therapeutic and prophylactic dose low molecular weight heparin for CrCl < 30 ml/min. Findings for patients with AF on dialysis were that warfarin or DOACs had a similar or higher risk of stroke compared to no anticoagulation. For patients with AF and CrCl < 30 ml/min not on dialysis, anticoagulation should be considered on an individual basis, with limited studies suggesting DOACs may have a preferable safety profile.. Further studies are still required, some ongoing, in patients with advanced CKD (CrCl < 30 ml/min) to identify the safest and most effective treatment options for VTE and AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Renal Insufficiency, Chronic; Venous Thromboembolism; Warfarin

Chronic kidney disease is common in patients with atrial fibrillation (AF) and is associated with heightened risks of stroke/systemic embolisation and bleeding. In this review we outline the evidence for AF stroke prevention in kidney disease, identify current knowledge gaps, and give recommendations for anticoagulation at various stages of chronic kidney disease. Overall, anticoagulation is underused. Warfarin use becomes increasingly difficult with advancing kidney disease, with difficulty maintaining international normalised ratio (INR) in therapeutic range, increased risk of intracranial and fatal bleeding compared to non-vitamin K oral anticoagulants (NOACs), and high rates of discontinuation. Similarly, the direct thrombin inhibitor dabigatran is not recommended as it is predominantly renally excreted with consequent increased plasma levels and bleeding risk with advanced kidney disease. The Factor Xa inhibitors apixaban and rivaroxaban have less renal excretion (25-35%), modest increases in plasma levels with advancing kidney disease, and are the preferred first line choice for anticoagulation in moderate kidney disease based on strong evidence from randomised clinical trials (RCTs). In severe kidney disease there is a paucity of RCT data, but extrapolation of the pharmacokinetic and RCT data for moderate kidney disease, and observational studies, support the considered use of dose-adjusted Factor Xa inhibitors unless the bleeding risk is prohibitive. In Australia, apixaban is approved for creatinine clearance down to 25 mL/min, and rivaroxaban down to 15 mL/min. For end-stage kidney disease warfarin is the only agent approved, but we recommend against anticoagulation (except in selected cases) due to high bleeding risk, multiple co-morbidities, and questionable benefit.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Australia; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Warfarin

Up to 20% of patients with chronic kidney disease have atrial fibrillation, and 40%-50% of atrial fibrillation patients suffer from chronic kidney disease. The 2 diseases share several risk factors and frequently coincide with each other. Both entities are associ ated with a prothrombotic state, which contributes to increased thromboembolic risk. Atrial fibrillation patients with chronic kidney disease have elevated risk of stroke, major bleeding, and mortality. Clinical risk scores, including CHA2DS2-VASc score, HAS-BLED score, or ORBIT score have a limited value in adverse clinical outcome risk stratification in patients with severe chronic kidney disease. However, the inclusion of renal function in the R(2)-CHA2DS2-VASc score does not improve significantly thromboembolic risk predic tion in atrial fibrillation. There is growing evidence suggesting that biomarkers, including N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin, cystatin C, or growth differentiation factor-15, might be helpful in the assessment of thromboembolic, bleeding, and/or mortality risk in atrial fibrillation patients with chronic kidney disease. The first-choice anticoagulant therapy is based on direct oral anticoagulants in this subgroup. The highest risk of adverse events is observed in end-stage renal disease, and in Europe, in contrast to the USA, solely warfarin is recommended in such atrial fibrillation patients. Treatment of atrial fibrillation patients with chronic kidney disease should be closely moni tored with the selection of right anticoagulant agents at the appropriate dose. The current review paper summarizes available evidence and the challenges of the management of atrial fibrillation patients with chronic kidney disease with practical implications.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Warfarin

Whether direct oral anticoagulants (DOACs) are more effective and safer than warfarin among Asian patients with non-valvular atrial fibrillation (NVAF) undergoing dialysis remains unclear.. We first compared the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding associated with DOACs compared with warfarin, in NVAF Asians undergoing dialysis using the Taiwan National Health Insurance Research Database (NHIRD) (Aim 1). Next, we searched PubMed and Medline from January 1, 2010 until January 31, 2020, to perform a systematic review and meta-analysis of all observational real-world studies comparing DOACs with warfarin specifically focused on NVAF patients with stage 4 or 5 chronic kidney disease undergoing dialysis (Aim 2). Finally, we tested the hypothesis whether AF patients undergoing dialysis treated with OACs (warfarin and DOACs) would be associated with lower risk of adverse clinical outcomes as compared to those without OACs using the Taiwan NHIRD (Aim 3).. From June 1, 2012, to December 31, 2017, a total of 3237 and 9263 NVAF patients comorbid with ESRD receiving oral anticoagulant (OACs) (490 on DOAC, 2747 on warfarin) or no OACs, respectively, were enrolled. Propensity score matching was used to balance covariates across the study groups. For the comparison of DOAC vs. warfarin (Aim 1), DOACs had comparable risks of IS/SE and major bleeding to warfarin in our present cohort. From the original 85 results retrieved, nine studies (including our study) with a total of 6490 and 22,494 patients treated with DOACs and warfarin were included in the meta-analysis, respectively. There were 5343 (82%) and 20,337 (90%) patients treated with DOACs and warfarin undergoing dialysis, respectively. The pooled meta-analysis also indicated no difference of the effectiveness (HR:0.90; [95%CI:0.74-1.10]; P = 0.32) and safety outcomes (HR:0.75; [95%CI:0.54-1.05]; P = 0.09) between DOACs and warfarin (Aim 2). For the comparison of OAC (+) vs. OAC (-) (Aim 3), OAC-treatment was associated with a higher risk of IS/SE (hazard ratio (HR):1.54; [95% confidential interval (CI):1.29-1.84];P < 0.0001) and comparable risk of major bleeding compared to those without OAC treatment.. DOACs did not provide benefit over warfarin regarding effectiveness and safety in AF patients undergoing dialysis. The use of OAC was not associated with a lower risk of IS/SE in ESRD AF patients when compared to those without OAC use.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Insurance Claim Review; Male; Patient Acuity; Renal Dialysis; Renal Insufficiency, Chronic; Stroke; Taiwan; Warfarin

Anticoagulant treatment in non-valvular atrial fibrillation (AF) patients with severe chronic kidney disease (CKD) or on dialysis remains a matter of debate. The object of this study was to quantify the benefit-risk profiles of rivaroxaban or apixaban versus warfarin in AF patients with stage 4-5 CKD or on dialysis.. A comprehensive search of the Cochrane Library, PubMed, Ovid, and Google Scholar databases was performed for eligible studies that comparing the effect and safety of rivaroxaban or apixaban versus warfarin in AF patients with stage 4-5 CKD or on dialysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were abstracted, and then pooled using a random-effects model.. A total of seven studies, one post hoc analysis of RCT and six observational cohorts, were included in this meta-analysis. Compared with warfarin use, the use of rivaroxaban or apixaban was significantly associated with reduced risks of all-cause death (HR = 0.82, 95% CI 0.72-0.93) and gastrointestinal bleeding (HR = 0.87, 95% CI 0.80-0.95). There were no significant differences in the risks of stroke or systemic embolism (rivaroxaban, HR = 0.71, 95% CI 0.43-1.19; apixaban, HR = 0.86, 95%CI 0.68-1.09) and major bleeding (rivaroxaban, HR = 0.96, 95% CI 0.64-1.45; apixaban, HR = 0.56, 95%CI 0.28-1.12).. Current evidence suggests that rivaroxaban or apixaban are safe and at least as effective as warfarin in patients with AF and stage 4-5 CKD or on dialysis.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Patient Acuity; Pyrazoles; Pyridones; Renal Dialysis; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Warfarin

BACKGROUND AND OBJECTIVE: Systematic reviews and meta-analyses of direct oral anticoagulants (DOACs) for patients with chronic kidney disease (CKD) or dialysis patients are lacking. We aimed to compare the efficacy and safety of DOACs and warfarin in patients with CKD requiring anticoagulation therapy.. We performed a systematic review and meta-analysis of six randomized controlled trials and 19 observational studies, with the inclusion criteria being a comparative study between DOACs and warfarin in patients with CKD or dialysis patients from database inception until August 2020. The efficacy outcomes were stroke, systemic embolism (SE), or venous thromboembolism (VTE), and the safety outcome was major bleeding.. Compared with warfarin, DOACs significantly reduced the risk of stroke/SE/VTE by 22% (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.64-0.95) and major bleeding by 17% (HR = 0.83, 95% CI 0.71-0.97). On comparing factor Xa inhibitors and dabigatran with warfarin separately, factor Xa inhibitors significantly reduced the risk of stroke/SE/VTE (HR = 0.78, 95% CI 0.62-0.98) and major bleeding (HR = 0.76, 95% CI 0.64-0.91) overall in patients. Comparing each DOACs with warfarin separately, apixaban was associated with a significantly better risk reduction of stroke/SE/VTE (25% risk reduction) and major bleeding (35% risk reduction) than warfarin. Compared with warfarin, DOACs significantly reduced the risk of stroke, SE, or VTE by 19% (HR = 0.81, 95% CI 0.68-0.97) in patients with CKD stage 3 and significantly lowered the risk of major bleeding by 31% (HR = 0.69, 95% CI 0.56-0.85) in patients with CKD stages 4-5.. In pooled, analyzed randomized controlled trials and observational studies, DOACs were associated with better efficacy in early CKD, as well as similar efficacy and safety outcomes to warfarin in patients with CKD stages 4-5 or dialysis patients. The results of patients with CKD stages 4-5 and dialysis patients were from observational studies. Well-designed randomized controlled trials focused on DOAC use in patients with CKD and dialysis patients are needed. PROSPERO register number: CRD42020150599, 6 February, 2020.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Stroke; Venous Thromboembolism; Warfarin

Chronic kidney disease (CKD) patients have a higher risk of cardiovascular (CVD) morbidity and mortality compared to the general population. The links between CKD and CVD are not fully elucidated but encompass both traditional and uremic-related risk factors. The term CKD-mineral and bone disorder (CKD-MBD) indicates a systemic disorder characterized by abnormal levels of calcium, phosphate, PTH and FGF-23, along with vitamin D deficiency, decreased bone mineral density or altered bone turnover and vascular calcification. A growing body of evidence shows that CKD patients can be affected by subclinical vitamin K deficiency; this has led to identifying such a condition as a potential therapeutic target given the specific role of Vitamin K in metabolism of several proteins involved in bone and vascular health. In other words, we can hypothesize that vitamin K deficiency is the common pathogenetic link between impaired bone mineralization and vascular calcification. However, some of the most common approaches to CKD, such as (1) low vitamin K intake due to nutritional restrictions, (2) warfarin treatment, (3) VDRA and calcimimetics, and (4) phosphate binders, may instead have the opposite effects on vitamin K metabolism and storage in CKD patients.

Topics: Calcium; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hyperparathyroidism; Osteocalcin; Phosphates; Renal Insufficiency, Chronic; Risk Factors; Vascular Calcification; Vitamin K; Vitamin K Deficiency; Warfarin

Vascular calcification is a known complication of chronic kidney disease (CKD). The prevalence of vascular calcification in patients with non-dialysis-dependent CKD stages 3-5 has been shown to be as high as 79% (20). Vascular calcification has been associated with increased risk for mortality, hospital admissions, and cardiovascular disease (6, 20, 50, 55). Alterations in mineral and bone metabolism play a pivotal role in the pathogenesis of vascular calcification in CKD. As CKD progresses, levels of fibroblast growth factor-23, parathyroid hormone, and serum phosphorus increase and levels of 1,25-(OH)

Topics: Animals; Anticoagulants; Arteries; Dietary Supplements; Humans; Iatrogenic Disease; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Signal Transduction; Vascular Calcification; Vitamin K; Vitamin K Deficiency; Warfarin

There is a lack of clear benefit and a potential risk of bleeding with direct oral anticoagulant (DOAC) use in chronic kidney disease (CKD) and dialysis patients with atrial fibrillation. The objective of this study was to evaluate how treatment with DOACs affects stroke and bleeding outcomes compared with warfarin or aspirin.. We conducted a systematic review of randomized controlled trials, cohort studies and case series, and searched electronic databases from 1946 to 2017. Studies evaluating stroke and bleeding outcomes with DOAC use in CKD and dialysis patients were included.. From 8008 studies, 10 met the inclusion criteria. For moderate CKD patients (estimated glomerular filtration rate  <60 mL/min/1.73 m2), there was no difference in stroke outcomes between dabigatran 110 mg [hazard ratio (HR) 0.78, 95% confidence interval (95% CI) 0.51-1.21], rivaroxaban (HR 0.82-0.84, 95% CI 0.25-2.69) and edoxaban (HR 0.87, 95% CI 0.65-1.18) versus warfarin. Dabigatran (150 mg twice daily) and apixaban reduced risk of stroke or systemic embolism significantly more than warfarin for moderate CKD patients (HR 0.55, 95% CI 0.34-0.89 and HR 0.61, 95% CI 0.39-0.94, respectively). Edoxaban and apixaban were associated with reduced major bleeding events (HR 0.50-0.76) compared with warfarin. Rivaroxaban and dabigatran 110 mg and 150 mg showed no significant difference in major bleeding versus warfarin. In hemodialysis (HD) patients, there was no difference in stroke outcomes between apixaban, dabigatran [relative risk (RR) 1.71, 95% CI 0.97-2.99] or rivaroxaban (RR 1.8, 95% CI 0.89-3.64) versus warfarin. In HD patients, rivaroxaban and dabigatran were associated with an increased major bleeding risk (RR 1.45-1.76), whereas there was no major bleeding difference with apixaban compared to warfarin.. The heterogeneity of major bleeding and stroke definitions of the 10 included studies.. Clinicians should continue to weigh the risk of stroke versus bleeding before prescribing DOACs in the CKD and dialysis population.

Topics: Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Dabigatran; Embolism; Glomerular Filtration Rate; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Treatment Outcome; Warfarin

Oral anticoagulants are commonly used drugs in patients with CKD and patients with ESKD to treat atrial fibrillation to reduce stroke and systemic embolism. Some of these drugs are used to treat or prevent deep venous thrombosis and pulmonary embolism in patients with CKD who undergo knee and hip replacement surgeries. Warfarin is the only anticoagulant that is approved for use by the Food and Drug Administration in individuals with mechanical heart valves. Each oral anticoagulant affects the coagulation profile in the laboratory uniquely. Warfarin and apixaban are the only anticoagulants that are Food and Drug Administration approved for use in patients with CKD and patients with ESKD. However, other oral anticoagulants are commonly used off label in this patient population. Given the acquired risk of bleeding from uremia, these drugs are known to cause increased bleeding events, hospitalization, and overall morbidity. Each anticoagulant has unique pharmacologic properties of which nephrologists need to be aware to optimally manage patients. In addition, nephrologists are increasingly asked to aid in the management of adverse bleeding events related to oral anticoagulant use in patients with CKD and patients with ESKD. This article summarizes the clinical pharmacology of these drugs and identifies knowledge gaps in the literature related to their use.

Topics: Administration, Oral; Anticoagulants; Antidotes; Antithrombins; Dabigatran; Factor Xa Inhibitors; Humans; International Normalized Ratio; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency, Chronic; Rivaroxaban; Thiazoles; Warfarin

Vitamin-K antagonists (VKA) have been the standard for oral anticoagulation. However, they carry several problems in older patients: frequent bleeding complications, complex management, risk of interactions with multiple drugs. Two classes of direct oral anticoagulants (DOA) are currently available in France: (a) direct thrombin inhibitors: dabigatran; and (b) direct factor Xa inhibitors: rivaroxaban, apixaban and others. Their management is easier: quickly effective after administration, they are given at fixed doses and do not need regular laboratory monitoring. Several randomized trials have shown that DOA are non-inferior to VKA for treating venous thromboembolic disease (prophylactic or curative treatment) and atrial fibrillation (prevention of associated embolisms). DOA might be also effective for long-term treatment of coronary disease, in some cases. No trial has specifically studied older patients. In the context of atrial fibrillation, subgroup analysis show similar results between patients above and below 75-years-old. Lower doses of dabigatran and apixaban should be used in many older people. All DOA are eliminated at least partly by kidneys. Their dose must be reduced in moderate renal failure (filtration glomerular rate (FGR) 30 to 50mL/min) and they are contraindicated in older patients with severe renal failure (FGR<30mL/min). DOA also have other problems: (a) important drug interactions are still possible, (b) the clinical application of specific coagulation tests need to be defined, (c) their safety in some subgroups of elderly patients, very different from patients included in clinical trials, is not known.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Contraindications, Drug; Dose-Response Relationship, Drug; Drug Interactions; Factor Xa Inhibitors; Heart Valve Prosthesis; Hemorrhage; Humans; Renal Insufficiency, Chronic; Risk Factors; Secondary Prevention; Stroke; Thromboembolism; Vitamin K; Warfarin

Direct oral anticoagulants (DOACs) have been shown to be superior to vitamin K antagonists (VKAs) in regards to safety and efficacy in numerous clinical trials and are now the preferred oral anticoagulant by multiple professional societies. However, patients with significant levels of organ dysfunction were excluded from all major clinical trials, leaving the clinical benefit in these subsets uncertain. Patients with chronic kidney disease (CKD) specifically often require anticoagulation for acute or long-term indications such as venous thromboembolism, atrial fibrillation, or mechanical heart valves. The efficacy and safety of anticoagulation in patients with renal failure is less certain, however, particularly with DOACs which have altered pharmacokinetics in patients with renal failure and limited observational data on their use in this population. In this review, we compile the most up to date data on the DOAC use in patients with CKD. DOAC use in patients with ESRD and advanced CKD is increasing despite the presence of a clear benefit, and with the potential for increased risk of bleeding compared to warfarin. Apixaban has the greatest amount of outcomes research supporting its use over warfarin in this patient population; however, further research on DOAC safety and efficacy in those with advanced CKD is still needed.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Europe; Hemorrhage; Humans; Kidney Failure, Chronic; Kidney Function Tests; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Severity of Illness Index; United States; Warfarin

Patients with CKD represent a vulnerable population where the risks of atrial fibrillation, ischemic stroke, and bleeding are all heightened. Although large randomized, controlled trials in the general population clearly demonstrate that the benefits of warfarin and direct-acting oral anticoagulants outweigh the risks of bleeding, no such studies have been conducted in patients when their creatinine clearance falls below 25-30 ml/min. Without randomized, controlled trial data, the role of anticoagulation in patients with CKD with atrial fibrillation remains unclear and our practice is informed by a growing body of imperfect literature such as observational and pharmacokinetic studies. This article aims to present a contemporary literature review of the benefits versus harms of anticoagulation in atrial fibrillation for patients with CKD stages 3, 4, 5, and 5 on dialysis. Although unanswered questions and areas of clinical equipoise remain, this piece serves to assist physicians in interpreting the complex body of literature and applying it to their clinical care.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Hemorrhage; Humans; Renal Insufficiency, Chronic; Risk Assessment; Stroke; Warfarin

Vitamin K is a composite term referring to a group of fat-soluble vitamins that function as a cofactor for the enzyme γ-glutamyl carboxylase (GGCX), which activates a number of vitamin K-dependent proteins (VKDPs) involved in haemostasis and vascular and bone health. Accumulating evidence demonstrates that chronic kidney disease (CKD) patients suffer from subclinical vitamin K deficiency, suggesting that this represents a population at risk for the biological consequences of poor vitamin K status. This deficiency might be caused by exhaustion of vitamin K due to its high requirements by vitamin K-dependent proteins to inhibit calcification.

Topics: Bone and Bones; Carbon-Carbon Ligases; Dietary Supplements; Humans; Nutritional Status; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Vitamin K; Vitamin K Deficiency; Warfarin

Data regarding the efficacy and safety of warfarin and non-vitamin K antagonist oral anticoagulant (NOAC) among patients with chronic kidney disease (CKD) remain scarce.. Fifteen studies (7 comparing NOAC vs warfarin and 8 comparing warfarin vs no anticoagulant) were identified comprising 78,053 patients. Warfarin (vs no anticoagulant) was associated with reduced risk of ischemic stroke (risk ratio [RR] = 0.68; 95% confidence interval [CI] 0.55-0.84]) and mortality (RR = 0.70; 95% CI 0.62-0.78). In comparison to warfarin, NOAC use lowered the risk of ICH (RR = 0.43; 95% CI 0.33-0.56), stroke. Among patients with CKD treated with oral anticoagulants, NOACs present with a more favorable safety and efficacy profile for various cardiovascular outcomes.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Intracranial Hemorrhages; Mortality; Renal Insufficiency, Chronic; Stroke; Warfarin

Atrial fibrillation (AF) is the most common cardiac rhythm disturbance and is associated with increased risk of thromboembolism. Oral anticoagulants are effective at reducing rates of thromboembolism in patients with AF in the general population. Patients with AF and concurrent chronic kidney disease (CKD) have higher risk of thromboembolism and bleeding compared with patients with normal renal function. Among moderate CKD and end-stage renal disease (ESRD) patients on chronic dialysis, the use of oral anticoagulants is controversial. Use of warfarin, while beneficial in non-CKD patients, raises a number of concerns such as increased bleeding risk, labile anticoagulant effect, and calciphylaxis, especially in the ESRD population. The newer direct oral anticoagulant (DOAC) agents have demonstrated comparable efficacy and improved safety profiles compared with coumadin but are not as well studied in the CKD population. This review highlights the efficacy and safety of coumadin and the DOACs for thromboembolism prophylaxis in non-valvular AF patients with CKD.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Renal Insufficiency, Chronic; Warfarin

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.. 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.. 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.. 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.

Topics: Animals; Anticoagulants; Humans; Renal Insufficiency, Chronic; Warfarin

Atrial fibrillation (AF) and chronic kidney disease (CKD) are increasingly prevalent in the general population and share common risk factors such as older age, hypertension and diabetes mellitus. The presence of CKD increases the risk of incident AF, and, likewise, AF increases the risk of CKD development and/or progression. Both conditions are associated with substantial thromboembolic risk, but patients with advanced CKD also exhibit a paradoxical increase in bleeding risk. In the landmark randomized clinical trials that compared non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin for thromboprophylaxis in patients with AF, the efficacy and safety of NOACs in patients with mild-to-moderate CKD were similar to those in patients without CKD. Dose adjustment of NOACs as per the prescribing label is required in this population. Owing to limited trial data, evidence-based recommendations for the management of patients with AF and severe CKD or end-stage renal disease on dialysis are lacking. Observational cohort studies have reported conflicting results, and the management of these particularly vulnerable patients remains challenging and requires careful assessment of stroke and bleeding risk and, where appropriate, use of warfarin with good-quality anticoagulation control.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Renal Insufficiency, Chronic; Risk Factors; Stroke; Warfarin

Anticoagulant-related nephropathy (ARN) is a newly recognized form of AKI in which overanticoagulation causes profuse glomerular hemorrhage, which manifests on renal biopsy as numerous renal tubules filled with red cells and red cell casts. The glomeruli show changes, but they are not sufficient to account for the glomerular hemorrhage. We were the first to study ARN, and since then, our work has been confirmed by numerous other investigators. Oral anticoagulants have been in widespread use since the 1950s; today, >2 million patients with atrial fibrillation take an oral anticoagulant. Despite this history of widespread and prolonged exposure to oral anticoagulants, ARN was discovered only recently, suggesting that the condition may be a rare occurrence. This review chronicles the discovery of ARN, its confirmation by others, and our animal model of ARN. We also provide new data on analysis of "renal events" described in the

Topics: Acute Kidney Injury; Administration, Oral; Animals; Anticoagulants; Creatinine; Disease Models, Animal; Humans; International Normalized Ratio; Kidney; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Risk Factors; Warfarin

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.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Geriatrics; Hemorrhage; Humans; Metabolic Clearance Rate; Renal Insufficiency, Chronic; Warfarin

Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, in CKD patients AF is associated with an increased risk of thromboembolism and stroke. However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance <25ml/min who were excluded from all pivotal phase 3 NOACs trials. This review focuses on the current pharmacokinetic, observational, and prospective data on NOACs in patients with moderate to advanced chronic kidney disease (creatinine clearance 15-49ml/min) and those on dialysis.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Prospective Studies; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Thiazoles; Thromboembolism; Warfarin

Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, AF is associated with an increased risk of thromboembolism and stroke, according to progressive decline of glomerular filtration rate (GFR). However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance <25 ml/min who were excluded from all pivotal phase 3 NOACs trials. This review focuses on the current pharmacokinetic, observational, and prospective data on NOACs in patients with advanced chronic kidney disease (creatinine clearance <25 ml/min) and those on dialysis.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Stroke; Thrombosis; Warfarin

Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin.. To assess the efficacy and safety of DOAC including apixaban, dabigatran, edoxaban, and rivaroxaban versus warfarin among AF patients with CKD.. We searched the Cochrane Kidney and Transplant Specialised Register (up to 1 August 2017) through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.. We included all randomised controlled trials (RCTs) which directly compared the efficacy and safety of direct oral anticoagulants (direct thrombin inhibitors or factor Xa inhibitors) with dose-adjusted warfarin for preventing stroke and systemic embolic events in non-valvular AF patients with CKD, defined as creatinine clearance (CrCl) or eGFR between 15 and 60 mL/min (CKD stage G3 and G4).. Two review authors independently selected studies, assessed quality, and extracted data. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for the association between anticoagulant therapy and all strokes and systemic embolic events as the primary efficacy outcome and major bleeding events as the primary safety outcome. Confidence in the evidence was assessing using GRADE.. Our review included 12,545 AF participants with CKD from five studies. All participants were randomised to either DOAC (apixaban, dabigatran, edoxaban, and rivaroxaban) or dose-adjusted warfarin. Four studies used a central, interactive, automated response system for allocation concealment while the other did not specify concealment methods. Four studies were blinded while the other was partially open-label. However, given that all studies involved blinded evaluation of outcome events, we considered the risk of bias to be low. We were unable to create funnel plots due to the small number of studies, thwarting assessment of publication bias. Study duration ranged from 1.8 to 2.8 years. The large majority of participants included in this study were CKD stage G3 (12,155), and a small number were stage G4 (390). Of 12,545 participants from five studies, a total of 321 cases (2.56%) of the primary efficacy outcome occurred per year. Further, of 12,521 participants from five studies, a total of 617 cases (4.93%) of the primary safety outcome occurred per year. DOAC appeared to probably reduce the incidence of stroke and systemic embolism events (5 studies, 12,545 participants: RR 0.81, 95% CI 0.65 to 1.00; moderate certainty evidence) and to slightly reduce the incidence of major bleeding events (5 studies, 12,521 participants: RR 0.79, 95% CI 0.59 to 1.04; low certainty evidence) in comparison with warfarin.. Our findings indicate that DOAC are as likely as warfarin to prevent all strokes and systemic embolic events without increasing risk of major bleeding events among AF patients with kidney impairment. These findings should encourage physicians to prescribe DOAC in AF patients with CKD without fear of bleeding. The major limitation is that the results of this study chiefly reflect CKD stage G3. Application of the results to CKD stage G4 patients requires additional investigation. Furthermore, we could not assess CKD stage G5 patients. Future reviews should assess participants at more advanced CKD stages. Additionally, we could not conduct detailed analyses of subgroups and sensitivity analyses due to lack of data.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Embolism; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Thiazoles; Warfarin

A 70-year-old man with relapsed/refractory chronic lymphocytic leukemia has multiple comorbidities including atrial fibrillation (on warfarin for anticoagulation), irritable bowel syndrome, and chronic renal insufficiency. Two years ago, he received bendamustine and rituximab as first-line therapy for chronic lymphocytic leukemia and achieved partial response, but now has relapsed. Fluorescence in situ hybridization cytogenetics reveals deletion 17p. Which novel agent would you recommend for this patient?

Topics: Aged; Antineoplastic Agents; Atrial Fibrillation; Chromosome Deletion; Chromosomes, Human, Pair 17; Comorbidity; Humans; Irritable Bowel Syndrome; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Renal Insufficiency, Chronic; Safety; Smith-Magenis Syndrome; Warfarin

The use of warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) can be problematic because of increased bleeding risk. We performed a systematic review and meta-analysis of observational studies that evaluated the use of warfarin in patients with AF and CKD to evaluate the risks of ischemic stroke/thromboembolism, major bleeding, and mortality.. PUBMED, EMBASE, CINAHL, ProQuest, and Google Scholar databases were electronically searched through January 12, 2015. Additionally, a manual search was performed for relevant references. Random-effects model was used to estimate the pooled hazard ratio (HR) with 95% CI. CKD was divided into non-end-stage CKD and end-stage CKD (on renal replacement therapy) and separate analyses were performed.. Thirteen publications from 11 cohorts (six retrospective and five prospective) including >48,500 total patients with >11,600 warfarin users were included in the meta-analysis. In patients with AF and non-end-stage CKD, warfarin resulted in a lower risk of ischemic stroke/thromboembolism (HR, 0.70; 95% CI, 0.54-0.89; P = .004) and mortality (HR, 0.65; 95% CI, 0.59-0.72; P < .00001), but had no effect on major bleeding (HR, 1.15; 95% CI, 0.88-1.49; P = .31). In patients with AF and end-stage CKD, warfarin had no effect on the risks of stroke (HR, 1.12; 95% CI, 0.69-1.82; P = .65) and mortality (HR, 0.96; 95% CI, 0.81-1.13; P = .60), but increased the risks of major bleeding (HR, 1.30; 95% CI, 1.08-1.56; P = .005).. Based on this meta-analysis, the use of warfarin for AF may have an unfavorable risk/benefit ratio in patients with end-stage CKD but not in those with non-end-stage CKD.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Kidney Failure, Chronic; Mortality; Proportional Hazards Models; Renal Insufficiency, Chronic; Renal Replacement Therapy; Risk Assessment; Stroke; Warfarin

To evaluate the safety of antithrombotic drugs used in patients with both atrial fibrillation (AF) and non-end-stage chronic kidney disease (NECKD).. A search was performed for studies on major bleeding outcomes in patients with concurrent AF and NECKD using Medline and Cochrane databases on 19th February, 2015. Fixed- or random-effects meta-analysis was adopted for evaluating pooled effect sizes according to whether heterogeneity existed.. Twelve articles were included for analysis. Three studies evaluated AF patients who took warfarin vs. placebo/antiplatelet drugs in the presence of NECKD. No significant difference in major bleeding risk was observed according to the pooled analysis using the random-effects model (RR: 1.05, 95% CI: 0.74-1.36). The risk of a composite of major bleeding outcomes was reduced by 19% in patients randomized to direct oral anticoagulants (DOACs) compared to dose-adjusted warfarin from pooled data of three randomized controlled trials with regard to AF and NECKD (RR: 0.81, 95% CI: 0.75-0.88). This superiority of DOACs to warfarin maintained until the renal function was severely impaired.. In patients with AF and NECKD, no significant increase in the incidence of major bleeding outcomes was observed in warfarin use compared with placebo/antiplatelet drugs. DOACs reduced the risk of major bleeding by 19% compared to warfarin and further data-exploration indicated that the risk did not increase as renal function deteriorated during the renal status of mild to moderate impairment.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Comorbidity; Female; Fibrinolytic Agents; Hemorrhage; Humans; Incidence; Male; Middle Aged; Renal Insufficiency, Chronic; Risk Factors; Thrombosis; Warfarin

Atrial fibrillation (AF) and chronic kidney disease (CKD) are disorders with increasing prevalence. The presence of CKD increases the risk of incident AF and vice versa, and the presence of AF may accelerate CKD progression. Nearly a third of patients with established CKD also have AF, whilst half of AF patients may have some degree of renal dysfunction. Both AF and CKD are associated with increased cardiovascular morbidity and mortality, including significantly increased risk of stroke or systemic embolism. Oral anticoagulant therapy (OAC), either with vitamin K antagonists or with non-vitamin K oral anticoagulants (NOACs) is essential to optimise prevention of stroke and systemic embolism in AF patients with one or more stroke risk factors, and NOACs are more convenient and generally safer than vitamin K antagonists mostly due to consistently reduced risk of intracranial bleeding. The use of OAC must be balanced against the risk of OAC-related bleeding, which depends on the presence of bleeding risk factors. Renal failure is a well-established bleeding risk factor and renal function should be routinely assessed in all patients presenting with AF. Since the risk of bleeding increases in parallel with CKD severity, the clinical decision to use OAC in AF patients with severe CKD may be challenging. In this review article we summarize the OAC agents currently used in clinical practice and discuss the role of NOACs for stroke prevention in patients with AF and CKD.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Dabigatran; Embolism; Humans; Renal Insufficiency, Chronic; Stroke; Warfarin

CKD is an independent risk factor for cardiovascular disease (CVD). Thus, patients with CKD often require treatment with cardiovascular drugs, such as antiplatelet, antihypertensive, anticoagulant, and lipid-lowering agents. There is significant interpatient variability in response to cardiovascular therapies, which contributes to risk for treatment failure or adverse drug effects. Pharmacogenomics offers the potential to optimize cardiovascular pharmacotherapy and improve outcomes in patients with CVD, although data in patients with concomitant CKD are limited. The drugs with the most pharmacogenomic evidence are warfarin, clopidogrel, and statins. There are also accumulating data for genetic contributions to β-blocker response. Guidelines are now available to assist with applying pharmacogenetic test results to optimize warfarin dosing, selection of antiplatelet therapy after percutaneous coronary intervention, and prediction of risk for statin-induced myopathy. Clinical data, such as age, body size, and kidney function have long been used to optimize drug prescribing. An increasing number of institutions are also implementing genetic testing to be considered in the context of important clinical factors to further personalize drug therapy for patients with CVD.

Topics: Adrenergic beta-Antagonists; Anticoagulants; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 Enzyme System; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Pharmacogenetics; Phenotype; Platelet Aggregation Inhibitors; Precision Medicine; Purinergic P2Y Receptor Antagonists; Renal Insufficiency, Chronic; Solute Carrier Proteins; Ticlopidine; Vitamin K Epoxide Reductases; Warfarin

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clinical Trials as Topic; Creatinine; Diabetes Complications; Drugs, Investigational; Europe; Female; Heart Failure; Hemorrhage; Humans; Hypertension; Myocardial Infarction; North America; Observational Studies as Topic; Pyrazoles; Pyridones; Registries; Renal Insufficiency, Chronic; Severity of Illness Index; Stroke; Tachycardia; Thrombophilia; Treatment Outcome; Warfarin

Nonvitamin K-dependent oral anticoagulant agents (NOACs) are currently recommended for patients with atrial fibrillation at risk for stroke. As a group, NOACs significantly reduce stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with warfarin. All NOACs are dependent on the kidney for elimination, such that patients with creatinine clearance <25 ml/min were excluded from all the pivotal phase 3 NOAC trials. It therefore remains unclear how or if NOACs should be prescribed to patients with advanced chronic kidney disease and those on dialysis. The authors review the current pharmacokinetic, observational, and prospective data on NOACs in patients with advanced chronic kidney disease (creatinine clearance <30 ml/min) and those on dialysis. The authors frame the evidence in terms of risk versus benefit to bring greater clarity to NOAC-related major bleeding and efficacy at preventing stroke specifically in patients with creatinine clearance <30 ml/min.

Topics: Anticoagulants; Atrial Fibrillation; Creatinine; Dabigatran; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney; Kidney Failure, Chronic; Pyrazoles; Pyridines; Pyridones; Renal Dialysis; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Thiazoles; Warfarin

Direct oral anticoagulants have recently emerged as an attractive choice for patients requiring anticoagulation treatment. They have a rapid onset of action and can be administered at fixed doses without the need for routine anticoagulation monitoring. They may present fewer interactions than warfarin but further experience is needed to assess the clinical significance of the interactions with cytochrome CYP3A and P-gp inhibitors/inducers. A higher rate of bleeding has been observed in association with antiplatelet agents or non-steroidal anti-inflammatory drugs. Their safety profile has not been sufficiently studied in the elderly, and in patients with liver disease or severe renal impairment. Dose adjustment is necessary in patients with moderate renal impairment and a higher bleeding rate has been observed in this subgroup, although not higher than with warfarin. The clinical settings that require monitoring of coagulation assays have not yet been specified. Reversal of their anticoagulant effect may be problematic in case of severe bleeding. Therefore, despite the obvious advantages of the direct oral anticoagulants, experience is still lacking for many patient subgroups in which they should be withheld awaiting more data.

Topics: Administration, Oral; Age Factors; Anticoagulants; Blood Coagulation; Food-Drug Interactions; Hemorrhage; Humans; Liver Diseases; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic; Warfarin

Anticoagulant-related nephropathy, a recently recognized entity, manifests as unexplained acute kidney injury in the setting of excessive anticoagulation with oral agents. Histologic findings in warfarin-related nephropathy include glomerular hemorrhage and renal tubular obstruction by red blood cells. Affected patients are at increased risk of mortality as well as irreversible kidney injury. Patients with chronic kidney disease are particularly vulnerable to this complication. Similar case reports of anticoagulant-related nephropathy have been linked to the more novel oral anticoagulant, dabigatran. Anticoagulant-related nephropathy has been successfully reproduced in rat models. These animal models shed light on the pathogenesis of the disease including the potential role of direct thrombin and protease-activated receptor-1 inhibition. Warfarin and dabigatran also cause an increase in systolic blood pressure in rats, a risk factor for developing nephropathy. This article reviews the current evidence for anticoagulant-related nephropathy and provides data for the suggested possible mechanisms underlying this adverse effect.

Topics: Acute Kidney Injury; Administration, Oral; Animals; Anticoagulants; Dabigatran; Disease Models, Animal; Humans; Rats; Renal Insufficiency, Chronic; Risk Factors; Warfarin

Chronic kidney disease and atrial fibrillation (AF) commonly coexist, and data suggest that renal patients have AF rates in excess of double that encountered in the general population. These patients are at increased risk of stroke, regardless of the presence or absence of AF. Furthermore, a lower GFR causes increased thromboembolic risk in patients with AF - independent of other risk factors. The dilemma facing clinicians treating this cohort of patients is that renal insufficiency confers both a thromboembolic and a bleeding risk. Renal disease also commonly coexists with other risk factors for stroke and bleeding such as hypertension and advanced age. Furthermore, bleeding risk tracks stroke risk and many risk factors are common to both thromboembolism and haemorrhage. Patients with severe renal impairment are also actively excluded from the majority of trials for stroke prevention in AF, including those trials which informed the development of stroke risk factor scoring schemes. Therefore, patients with renal disease and AF present a unique management challenge. The available data suggests that the benefit from warfarin in terms of stroke reduction is not as clear as in the general population, and there is an increased risk of bleeding complications and even ectopic vascular calcification. Thus, it is problematic to extrapolate the benefits of warfarin in the general population to a subgroup that has been actively excluded from clinical trials. The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion. There is a need for large randomised control trials in patients with renal insufficiency and on haemodialysis to provide a bank of high-quality scientific data on which clinicians can base their management decisions. Until then, we must adopt a pragmatic approach which involves careful consideration of the relative risk of stroke and bleeding in each individual patient.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Comorbidity; Dabigatran; Disease Management; Embolism; Female; Fibrinolytic Agents; Hemorrhage; Humans; Hypertension; Intracranial Embolism; Male; Morpholines; Patient Selection; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Risk; Risk Factors; Rivaroxaban; Severity of Illness Index; Stroke; Thiophenes; Thrombophilia; Warfarin

Patients with atrial fibrillation (AF) and chronic kidney disease (CKD) are individually associated with a higher incidence of stroke as compared with the general population. Over the last two decades, an increase in prevalence of AF is seen in patients with CKD. While long-term anticoagulation with warfarin is well established to reduce the risk of thromboembolic event in patients with AF, its safety and efficacy has not been documented in patients with severe CKD.. In this review, the authors analyze the risk and benefit of long term anticoagulation across the spectrum of AF patients with CKD and explore the role of novel agents in this unique patient population. A Medline search of the English literature published between 1980 and 2012 was performed using the heading 'chronic kidney disease' combined with 'atrial fibrillation', 'hemodialysis', 'warfarin', 'anticoagulation' and 'new oral anticoagulants'.. Long-term anticoagulation with warfarin under strict monitoring appears to be the cornerstone of therapy in patients with CKD to prevent stroke. Further research is warranted to explore the safety and efficacy of newer anticoagulant agents in these high-risk patients in order to reduce the incidence of disabling stroke.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Monitoring; Hemorrhage; Humans; Patient Selection; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Treatment Outcome; Warfarin

As chronic kidney disease (CKD) is a contraindication to the use of the new anticoagulants, the vitamin K antagonists (VKA) are still valid in patients with CKD, though their use may be harmful. During overanticoagulation, some patients can develop acute kidney injury (AKI), especially those with CKD, by obstruction of the renal tubules and Bowman's spaces by erythrocytes. In addition, VKA increase atherogenesis through vitamin K deficiency, which is essential for the carboxylation of proteins that inhibit calcification of vessels. Eventually, hemodialysed patients under VKA have an increased risk of stroke, especially those over 75 years of age. Therefore anticoagulation with VKA in patients with CKD should be carefully implemented and its monitoring more frequent than in non-CKD patients.

Topics: 4-Hydroxycoumarins; Acute Kidney Injury; Anticoagulants; Atherosclerosis; Blood Coagulation Disorders; Cerebrovascular Disorders; Coumarins; Humans; Indenes; Renal Insufficiency, Chronic; Vitamin K; Warfarin

Topics: Aged; Endpoint Determination; Factor Xa Inhibitors; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Incidence; Kidney Function Tests; Male; Middle Aged; Renal Insufficiency, Chronic; Risk Assessment; Stroke; Thromboembolism; Warfarin

Veverimer is a polymer being developed as a potential treatment of metabolic acidosis in patients with chronic kidney disease. Veverimer selectively binds and removes hydrochloric acid from the gastrointestinal tract, resulting in an increase in serum bicarbonate. Veverimer is not systemically absorbed, so potential drug-drug interactions (DDIs) are limited to effects on the absorption of other oral drugs through binding to veverimer in the gastrointestinal tract or increases in gastric pH caused by veverimer binding to hydrochloric acid. In in vitro binding experiments using a panel of 16 test drugs, no positively charged, neutral, or zwitterionic drugs bound to veverimer. Three negatively charged drugs (furosemide, aspirin, ethacrynic acid) bound to veverimer; however, this binding was reduced or eliminated in the presence of normal physiologic concentrations (100-170 mM) of chloride. Veverimer increased gastric pH in vivo by 1.5-3 pH units. This pH elevation peaked within 1 hour and had returned to baseline after 1.5-3 hours. Omeprazole did not alter the effect of veverimer on gastric pH. The clinical relevance of in vitro binding and the transient increase in gastric pH was evaluated in human DDI studies using two drugs with the most binding to veverimer (furosemide, aspirin) and two additional drugs with pH-dependent solubility effecting absorption (dabigatran, warfarin). None of the four drugs showed clinically meaningful DDI with veverimer in human studies. Based on the physicochemical characteristics of veverimer and results from in vitro and human studies, veverimer is unlikely to have significant DDIs. SIGNIFICANCE STATEMENT: Patients with chronic kidney disease, who are usually on many drugs, are vulnerable to drug-drug interactions (DDIs). The potential for DDIs with veverimer was evaluated based on the known site of action and physicochemical structure of the polymer, which restricts the compound to the gastrointestinal tract. Based on the findings from in vitro and human studies, we conclude that veverimer is unlikely to have clinically significant DDIs.

Topics: Absorption, Physicochemical; Acidosis; Administration, Oral; Adolescent; Adult; Aspirin; Cross-Over Studies; Dabigatran; Drug Interactions; Ethacrynic Acid; Female; Furosemide; Gastrointestinal Absorption; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Polymers; Polypharmacy; Renal Insufficiency, Chronic; Solubility; Warfarin; Young Adult

Compared with the general population, patients with advanced chronic kidney disease have a >10-fold higher burden of atrial fibrillation. Limited data are available guiding the use of nonvitamin K antagonist oral anticoagulants in this population.. We compared the safety of apixaban with warfarin in 269 patients with atrial fibrillation and advanced chronic kidney disease (defined as creatinine clearance [CrCl] 25 to 30 mL/min) enrolled in the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). Cox proportional models were used to estimate hazard ratios for major bleeding and major or clinically relevant nonmajor bleeding. We characterized the pharmacokinetic profile of apixaban by assessing differences in exposure using nonlinear mixed effects models.. Among patients with atrial fibrillation and CrCl 25 to 30 mL/min, apixaban caused less bleeding than warfarin, with even greater reductions in bleeding than in patients with CrCl >30 mL/min. We observed substantial overlap in the range of exposure to apixaban 5 mg twice daily for patients with or without advanced chronic kidney disease, supporting conventional dosing in patients with CrCl 25 to 30 mL/min. Randomized, controlled studies evaluating the safety and efficacy of apixaban are urgently needed in patients with advanced chronic kidney disease, including those receiving dialysis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00412984.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Female; Hemorrhage; Humans; Male; Proportional Hazards Models; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Warfarin

Chronic kidney disease (CKD) complicates warfarin anticoagulation partially through its effect on CYP2C9 activity. Tecarfarin, a novel vitamin K antagonist, is not metabolized by CYP2C9. To evaluate the effect of CKD on their metabolism, we measured PK parameters of warfarin and tecarfarin in subjects with and without CKD. CKD subjects with estimated glomerular filtration rate < 30 mL/min not on dialysis (

Topics: Adult; Aged; Anticoagulants; Area Under Curve; Benzoates; Blood Coagulation; Coumarins; Cross-Over Studies; Cytochrome P-450 CYP2C9; Drug Interactions; Drug Monitoring; Female; Glomerular Filtration Rate; Half-Life; Humans; Kidney; Male; Metabolic Clearance Rate; Middle Aged; Patient Safety; Pharmacogenomic Variants; Renal Insufficiency, Chronic; Risk Assessment; Severity of Illness Index; Treatment Outcome; United States; Warfarin; Young Adult

The review shows the prevalence of atrial fibrillation (AF) in patients with chronic kidney disease (CKD), depending on the severity of the disease. Patients with non-valvular AF and CKD have a significantly increased risk of both bleeding and thromboembolic complications, and death from all causes. Evaluation of the results of randomized clinical trials (RCTs), meta-analyzes of RCTs demonstrated the advantages of the new oral anticoagulants (NOAC), such as dabigatran, rivaroxaban, apixaban, compared with warfarin in reducing the risk of bleeding in patients with AF and CKD in predialysis stage. According to experimental and clinical studies, warfarin can promote renal vascular calcification. With the deterioration of filtration renal function during treatment with anticoagulants in patients with AF on the results of ROCKET AF study found that rivaroxaban is more preferable than warfarin in reducing the risk of stroke and systemic embolism without increasing the risk of bleeding. The absence of RCT data complicates the choice of anticoagulant therapy in patients with CKD on hemodialysis, although the NOAC approved by the Office of Quality Control Food and Drug US drugs (FDA) for the use of patients in this category. According to the instruction drugs rivaroxaban and apixaban are allowed to use in patients with end-stage CKD with creatinine clearance not less than 15 ml/min.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Pyridones; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Warfarin

Topics: Aged; Atrial Fibrillation; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Valves; Humans; Japan; Male; Middle Aged; Prospective Studies; Renal Insufficiency, Chronic; Risk Assessment; Rivaroxaban; Treatment Outcome; Warfarin

Atrial fibrillation (AF) is common among patients with impaired renal function. Apixaban, a novel oral anticoagulant with partial renal excretion, was compared with warfarin and reduced the rate stroke, death and bleeding in the ARISTOTLE trial. We evaluated these outcomes in relation to renal function.. Baseline glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations as well as cystatin C measurements. According to baseline Cockcroft-Gault, there were 7518 patients (42%) with an estimated GFR (eGFR) of >80 mL/min, 7587 (42%) between >50 and 80 mL/min, and 3017 (15%) with an eGFR of ≤50 mL/min. The rate of cardiovascular events and bleeding was higher at impaired renal function (≤80 mL/min). Apixaban was more effective than warfarin in preventing stroke or systemic embolism and reducing mortality irrespective of renal function. These results were consistent, regardless of methods for GFR estimation. Apixaban was associated with less major bleeding events across all ranges of eGFRs. The relative risk reduction in major bleeding was greater in patients with an eGFR of ≤50 mL/min using Cockcroft-Gault {hazard ratio (HR) 0.50 [95% confidence interval (CI) 0.38-0.66], interaction P = 0.005} or CKD-EPI equations [HR 0.48 (95% CI 0.37-0.64), interaction P = 0.003].. In patients with AF, renal impairment was associated with increased risk of cardiovascular events and bleeding. When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function. Patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban.

Topics: Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Glomerular Filtration Rate; Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Risk Factors; Stroke; Treatment Outcome; Warfarin

Chronic kidney disease (CKD) is characterized by increased interstitial fibrosis and tubular atrophy (IFTA) in the kidney. Chronic hematuria is a hallmark of several human kidney diseases and often is seen in patients on anticoagulation therapy. We had previously demonstrated that chronic hematuria associated with warfarin increases IFTA in 5/6 nephrectomy (5/6NE) rats, and such treatment increases reactive oxygen species (ROS) in the kidney. The goal of this study was to evaluate the effects of the antioxidant N-acetylcysteine (NAC) on the progression of IFTA in 5/6NE mice. 5/6NE C57BL/6 and 5/6NE 129S1/SvImJ mice were treated with warfarin alone or with warfarin and NAC for 23 weeks. Serum creatinine (SCr), hematuria, blood pressure (BP), and ROSs in the kidney were measured; kidney morphology was evaluated. Warfarin doses were titrated to achieve prothrombin time (PT) increase to the levels seen with therapeutic human doses. Warfarin treatment resulted in an increased SCr, systolic BP, hematuria, expression of TGF-ß and ROS in the kidney in both mouse strains. Tumor necrosis factor alpha (TNF-ɑ) levels in the serum were increased in 5/6NE mice treated with warfarin. IFTA was increased as compared with control 5/6NE mice, and this increase in IFTA was more prominent in 129S1/SvImJ than in C57BL/6 mice. NAC ameliorated the warfarin-associated increase in SCr and BP but not hematuria. IFTA, TGF-ß, and ROS in the kidney as well as TNF-ɑ levels in the serum were reduced in mice treated with NAC and warfarin as compared to mice treated with warfarin alone. NAC mitigates the increase in SCr and IFTA in mice with chronic hematuria by reducing oxidative stress in the kidney. This data open novel possibilities for treatments in CKD patients.

Topics: Acetylcysteine; Animals; Fibrosis; Hematuria; Humans; Kidney; Mice; Mice, Inbred C57BL; Nephrectomy; Rats; Reactive Oxygen Species; Renal Insufficiency, Chronic; Tumor Necrosis Factor-alpha; Warfarin

Warfarin treatment quality is calculated as time in therapeutic range (TTR). TTR ≥ 70 % is considered reducing the risk of adverse events for patients with atrial fibrillation (AF). The association of TTR and adverse events in chronic kidney disease (CKD) is however poorly investigated. The aim is to explore this further.. Swedish cohort study based on national healthcare registers between 2009 and 2018, including Swedish Renal Registry, Swedish Stroke Register and AuriculA - the Swedish national quality register for AF and anticoagulation. Investigating the effect of individual TTR (iTTR) and iTTR ≥ 70 % versus <70 % on the risk of ischemic stroke, major bleeding and death for patients with CKD GFR category 3-5 (G3-G5) including patients on dialysis (G5D) and non-valvular AF (NVAF).. Of 2379 included patients 21.9 % had G3, 47.5 % G4, 10.8 % G5 and 19.8 % G5D. TTR in G3 was 75.6 %, G4 72.2 %, G5 67.6 % and G5D 62.0 %. Increase by 10 percentage points iTTR conferred lower risk of major bleeding, ischemic stroke and death for all patients (hazard ratio 0.91 (95 % Confidence interval 0.87-0.94), 0.92 (0.85-0.99) and 0.88 (0.85-0.90)). iTTR≥ 70 % versus <70 % was associated with lower risk of bleeding and death in all patients (0.63 (0.51-0.77) and (0.51 (0.43-0.61)), and a non-significant tendency towards lower stroke risk (0.67 (0.43-1.06)).. Warfarin treatment quality worsens with decreasing GFR. Higher iTTR confers lower risk of bleeding, ischemic stroke and death in patients with NVAF and G3-G5D. iTTR ≥ 70 % was associated with better safety profile. Close monitoring of patients with CKD on warfarin is recommended.

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Hemorrhage; Humans; Ischemic Stroke; Renal Insufficiency, Chronic; Stroke; Warfarin

There has been limited evidence reported about the outcomes of oral anticoagulants among patients with venous thromboembolism (VTE) and chronic kidney disease (CKD), especially those with stage V/end-stage renal disease (ESRD). This retrospective cohort analysis of five U.S. claims databases evaluated the risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB) for apixaban versus warfarin among VTE patients diagnosed with CKD, including ESRD. Inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Hazard ratios (HRs) were calculated for recurrent VTE, MB, and CRNMB among patients with CKD who experienced an index VTE. An interaction analysis was conducted to evaluate treatment effects across different stages of CKD. A total of 29,790 VTE patients with CKD were selected for analyses, of whom 10,669 (35.8%) initiated apixaban and 19,121 (64.2%) initiated warfarin. Among IPTW-balanced patient cohorts, the apixaban group had significantly lower risk of recurrent VTE (HR: 0.78; 95% confidence interval [CI]: 0.66-0.92), MB (HR: 0.76; 95% CI: 0.65-0.88), and CRNMB (HR: 0.86; 95% CI: 0.80-0.93) than the warfarin group. When stratified by CKD stage (stage I/II: 8.2%; stage III: 49.4%; stage IV: 12.8%; stage V/ESRD: 12.0%; stage unspecified: 17.6%), no significant interaction was observed for effects of apixaban versus warfarin on recurrent VTE or MB. In summary, apixaban was associated with a significantly lower risk of recurrent VTE and MB than warfarin among VTE patients with CKD. CKD stages did not have significant impact on treatment effects for recurrent VTE and MB.

Topics: Anticoagulants; Hemorrhage; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Retrospective Studies; Venous Thromboembolism; Warfarin

Evidence is needed on the impact of anticoagulation therapy on kidney function in patients with atrial fibrillation (AF). The objective of this analysis, which is part of the CALLIPER study, was to investigate the risk of worsening kidney function with rivaroxaban 15 mg once daily compared with warfarin in patients with AF and moderate-to-severe chronic kidney disease (CKD) in routine clinical practice in the United States.. CALLIPER was an observational, retrospective, new-user cohort study. Adult patients with AF in the US IBM Watson MarketScan databases who newly initiated anticoagulation with rivaroxaban 15 mg once daily or warfarin between January 2013 and December 2017 were included. Comparative analysis was performed using Cox proportional hazards regression after adjustment for potential confounding by the stabilized inverse probability of treatment weighting approach and propensity score matching. One of the main study outcomes was worsening kidney function (composite of progression to CKD stage 5, kidney failure, or need for dialysis), besides traditional AF-related outcomes.. The cohort included 7368 patients: 5903 (80.1%) initiating warfarin and 1465 (19.9%) initiating rivaroxaban 15 mg once daily. Rivaroxaban 15 mg was associated with a significant 47% reduction in the risk of worsening kidney function versus warfarin (hazard ratio 0.53; 95% confidence interval 0.35-0.78). Similar results were observed in the subgroup of patients with type 2 diabetes.. Rivaroxaban 15 mg may be associated with a lower risk of worsening kidney function as compared with warfarin in the atrial fibrillation population with moderate-to-severe CKD.. NCT03359876.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus, Type 2; Humans; Kidney; Renal Insufficiency, Chronic; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; United States; Warfarin

Non-vitamin-K dependent oral anti-coagulants (NOAC) are the current therapeutic standard for preventing strokes in patients with atrial fibrillation (AF) and should be preferred over vitamin K antagonists (VKA) in this indication. This recommendation applies also to patients with VHF and concomitant chronic kidney disease (CKD). Real World Evidence (RWE), i. e., structured data from clinical practice, extends and confirms the clinical evidence generated in more formalized clinical trials with NOAC and VKA. In addition, RWE in respect to the indication showed that the superiority of NOAC versus the VKA warfarin can also be extrapolated to phenprocoumon, the commonly used VKA in Germany. Furthermore, data include evidence that the typical progression of CKD appears to be less pronounced in individuals treated with NOAC compared to those treated with VKA.. Die momentanen Leitlinien empfehlen Nicht-Vitamin-K-abhängige orale Antikoagulanzien (NOAK) als Therapiestandard für die Schlaganfallprophylaxe bei Patienten mit Vorhofflimmern (VHF) und sind daher den Vitamin-K-Antagonisten (VKA) vorzuziehen. Diese Empfehlung gilt auch für Patienten mit VHF und chronischer nicht dialysepflichtiger Niereninsuffizienz. Sogenannte Real-World-Evidenz (RWE), also Daten aus der klinischen Praxis, erweitert und bestätigt die zugrunde liegende klinische Evidenz, die in den stärker formalisierten klinischen Prüfungen mit NOAK und VKA, hier ausschließlich Warfarin, gewonnen wurde. Darüber hinaus zeigte die RWE, dass die Überlegenheit der NOAK gegenüber dem VKA Warfarin auch für Phenprocoumon gilt, dem in Deutschland gebräuchlichsten VKA. Auch fanden sich Hinweise, dass bei Patienten mit chronischen Nierenerkrankungen das Fortschreiten der Nierenfunktionsstörung unter Behandlung mit NOAK geringer ausfallen kann als unter VKA.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Renal Insufficiency, Chronic; Stroke; Vitamin K; Warfarin

Data on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in relation to the risk of cardiovascular (CV) disease and renal protection among patients with atrial fibrillation (AF), are relatively sparse. We aimed to compare the effectiveness and safety of NOACs with those of warfarin for vascular protection in a large-scale, nationwide Asian population with AF.. Patients with AF who were prescribed oral anticoagulants according to the Korean Health Insurance Review and Assessment database between 2014 and 2017 were analyzed. The warfarin and NOAC groups were balanced using propensity score weighting. Clinical outcomes included ischemic stroke, myocardial infarction, angina pectoris, peripheral artery disease, chronic kidney disease (CKD), end-stage renal disease (ESRD), CV death, and all-cause death. NOAC use was associated with a lower risk of angina pectoris (HR, 0.79 [95% CI, 0.69-0.89] p<0.001), CKD stage 4 (HR, 0.5 [95% CI, 0.28-0.89], p = 0.02), and ESRD (HR, 0.15[95% CI, 0.08-0.32], p<0.001) than warfarin use. NOACs and warfarin did not significantly differ with respect to stroke reduction (HR, 1.05 [95% CI, 0.88-1.25], p = 0.19). NOAC use was associated with a lower risk of intracranial hemorrhage (HR, 0.6 [95% CI, 0.44-0.83], p = 0.0019), CV death (HR, 0.55 [95% CI, 0.43-0.70], p<0.001), and all-cause death (HR, 0.6 [95% CI, 0.52-0.69], p<0.001) than warfarin use.. NOACs were associated with a significantly lower risk of adverse CV and renovascular outcomes than warfarin in patients with AF.

Topics: Administration, Oral; Angina Pectoris; Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Stroke; Warfarin

The aim was to identify sex-specific factors linked with oral anticoagulant initiation in a cohort of patients with atrial fibrillation using administrative data from Quebec (Canada) between 2014 and 2017. Cohort entry defined as new users, that is, no claims in last 12 months, a cohort of 32 050 patients was stratified in two groups, that is, women and men. Multivariable regression models were used to identify factors of initiations for low- and standard-dose direct oral anticoagulants (DOACs) versus warfarin, and low- versus standard-dose DOACs. In both sexes, warfarin initiation decreased and DOAC initiation increased, with year of initiation as major factors of DOACs use. In 2017, the increase was of 2- to 4-fold and 3- to 8-fold for low- and standard-dose DOACs (vs. warfarin), respectively. The proportion of patients starting on a low-dose DOAC was higher in women than men. Older age for both sexes and CHADS

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Hemorrhage; Humans; Male; Renal Insufficiency, Chronic; Rivaroxaban; Warfarin

In non-valvular atrial fibrillation (NVAF) patients with chronic kidney disease (CKD), rivaroxaban was not inferior to warfarin in preventing stroke and systemic embolism. However, a comparative evaluation of the cost-effectiveness of rivaroxaban and warfarin therapies for NVAF patients at different renal function levels has not yet been reported, and this study aimed to estimate the cost-effectiveness of rivaroxaban compared with warfarin in Chinese NVAF patients with CKD.. A Markov model was constructed to estimate quality-adjusted life years (QALYs) and lifetime costs associated with the use of rivaroxaban relative to warfarin in patients with NVAF at different estimated glomerular filtration rate (eGFR) levels as follows: 30 to <50, 50 to <80 and ≥80 mL/min. Input parameters were sourced from the clinical literature. Probabilistic sensitivity analyses were performed to assess model uncertainty.. The incrementalQALYs with rivaroxaban was slightly increased by approximately 0.3 QALY as compared with that with warfarin in all the subgroups, resulting in an ICER of $9,736/QALY (eGFR, 30 to <50 mL/min), $9,758/QALY (50 to <80 mL/min) and $9,969/QALY (≥80 mL/min). The probabilistic sensitivity analysis suggested a chance of >80% that the ICER would be lower than the willingness-to-pay threshold of three times the GDP of China in 2019 in all the subgroups. Results were consistent even under the assumption of anticoagulant discontinuation after major bleeding events. The model was most sensitive to event-free-related utility and survival rates.. The existing evidence supports the cost-effectiveness of rivaroxaban therapy as an alternative anticoagulant to warfarin for patients with NVAF at different renal function levels.

Topics: Anticoagulants; Atrial Fibrillation; China; Cost-Benefit Analysis; Factor Xa Inhibitors; Glomerular Filtration Rate; Health Expenditures; Hemorrhage; Humans; Models, Econometric; Polyketides; Quality-Adjusted Life Years; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Warfarin

Comparing kidney disease progression among patients treated with direct oral anticoagulants (DOACs) versus warfarin has not been well studied. We hypothesized that apixaban would be associated with lower risks of progression of chronic kidney disease (CKD) and progression to incident kidney failure than warfarin in patients with atrial fibrillation (AF).. Retrospective cohort study.. Medicare recipients with stage 3, 4, or 5 CKD and incident AF who received a new prescription for apixaban or warfarin from 2013 through 2017.. Apixaban or warfarin.. Progression to incident kidney failure or, separately, to a more advanced stage of CKD.. Marginal structural cause-specific proportional hazards models with inverse probability weighting to estimate marginal hazard ratios (HRs) for each outcome. HRs compared apixaban to warfarin in intention-to-treat and censored-at-drug-switch analyses.. 12,816 individuals met inclusion criteria (50.3% received apixaban; 49.7% received warfarin). After weighting, the mean age of the cohort was 80 ± 7 years, 51% were women, and 88% were White. Approximately 84% had stage 3, 15% had stage 4, and 1% had stage 5 CKD. In the intention-to-treat analysis, apixaban, relative to warfarin, was associated with an HR of developing incident kidney failure of 0.98 (95% confidence interval [CI], 0.79-1.22) and of CKD stage progression of 0.90 (95% CI, 0.82-0.99). Corresponding HRs for censored-at-drug-switch analyses were 0.81 (95% CI, 0.56-1.17) and 0.81 (95% CI, 0.70-0.92). Results were similar for a series of subgroup and sensitivity analyses.. CKD was defined based on diagnosis codes from claims; findings may not be generalizable to non-Medicare CKD populations.. Apixaban, compared with warfarin, was associated with lower risk of CKD stage progression, but not with incident kidney failure.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Disease Progression; Factor Xa Inhibitors; Female; Humans; Ischemic Stroke; Kidney Failure, Chronic; Male; Medicare; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Retrospective Studies; Severity of Illness Index; United States; Warfarin

While direct oral anticoagulants (DOACs) are considered safe among patients without chronic kidney disease (CKD), the evidence is conflicting as to whether they are also safe in the CKD and end-stage kidney disease (ESKD) population. In this observational cohort study, we examined whether DOACs are a safe alternative to warfarin across CKD stages for a variety of anticoagulation indications.. Individuals on DOACs or warfarin were identified from OptumLabs® Data Warehouse (OLDW), a longitudinal dataset with de-identified administrative claims, from 2010 to 2017. Cox models with sensitivity analyses were used to assess the risk of cardiovascular disease and bleeding outcomes stratified by CKD stage.. Among 351,407 patients on anticoagulation, 45% were on DOACs. CKD stages 3-5 and ESKD patients comprised approximately 12% of the cohort. The most common indications for anticoagulation were atrial fibrillation (AF, 44%) and venous thromboembolism (VTE, 23%). DOACs were associated with a 22% decrease in the risk of cardiovascular outcomes (HR 0.78, 95% CI: 0.77-0.80, p < 0.001) and a 10% decrease in the risk of bleeding outcomes (HR 0.90, 95% CI: 0.88-0.92, p < 0.001) compared to warfarin after adjustment. On stratified analyses, DOACs maintained a superior safety profile across CKD stages. Patients with AF on DOACs had a consistently lower risk of cardiovascular and bleeding events than warfarin-treated patients, while among other indications (VTE, peripheral vascular disease, and arterial embolism), the risk of cardiovascular and bleeding events was the same among DOAC and warfarin users.. DOACs may be a safer alternative to warfarin even among CKD and ESKD patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Cohort Studies; Female; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Insufficiency, Chronic; Severity of Illness Index; United States; Warfarin

This study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC).. We retrospectively reviewed  10,320 patients who underwent ESD for EGC during November 2013-October 2016. We evaluated overall bleeding rates and their inter-group differences. Factors associated with early/late (cut-off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated.. Overall, the post-ESD bleeding rate was 4.7% (489/10 320); the median time to post-ESD bleeding was 4 days. The post-ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1).. We revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC.

Topics: Anticoagulants; Aspirin; Endoscopic Mucosal Resection; Fibrinolytic Agents; Gastric Mucosa; Humans; Japan; Male; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Stomach Neoplasms; Thienopyridines; Thromboembolism; Warfarin

Topics: Administration, Oral; Antifibrinolytic Agents; Antithrombins; Atrial Fibrillation; Consensus; Delphi Technique; Diabetes Complications; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Stroke; Vascular Diseases; Warfarin

Patients with atrial fibrillation (AF) commonly have impaired renal function. The safety and efficacy of direct oral anticoagulants (DOACs) in patients with chronic kidney disease (CKD) and end-stage renal disease has not been fully elucidated. This study evaluated and compared the safety outcomes of DOACs versus warfarin in patients with nonvalvular AF and concomitant CKD. Patients in our health system with AF prescribed oral anticoagulants during 2010 to 2017 were identified. All-cause mortality, bleeding and hemorrhagic, and ischemic stroke were evaluated based on degree of renal impairment and method of anticoagulation. There were 21,733 patients with a CHA

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Pennsylvania; Platelet Aggregation Inhibitors; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Survival Rate; Warfarin

Topics: Aged; Anticoagulants; Blood Coagulation; Female; Hemorrhage; Hospitals, Veterans; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Stroke; Venous Thromboembolism; Veterans; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Renal Insufficiency, Chronic; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Renal Insufficiency, Chronic; Warfarin

There is limited evidence on the effectiveness and safety of direct-acting oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD). This study compared the risks of ischemic stroke/systemic embolism (ISSE) and major bleeding in patients with NVAF and stage IV-V CKD treated with rivaroxaban or warfarin.. Patients with NVAF and stage IV-V CKD who initiated rivaroxaban or warfarin treatment between November 2011 and June 2018 were selected from the Optum® Deidentified Electronic Health Record Database. Propensity score matching was used to balance rivaroxaban and warfarin patients on 112 measured baseline covariates. ISSE and major bleeding events over 2 years following treatment initiation were ascertained with validated end point definitions. Outcomes were analyzed as time-to-event data using Kaplan-Meier survival estimators and Cox regression.. A total of 781 eligible rivaroxaban-treated patients were propensity score-matched to 1,536 warfarin-treated patients; baseline covariates were well balanced after matching (absolute standardized differences <0.1). The average patient age was 80 years; 60.5% were female; 81.3% and 18.7% had CKD stage IV and V, respectively. Hazard ratios for rivaroxaban compared to warfarin were 0.93 (95% CI 0.46-1.90, P = .85) for the risk of ISSE and 0.91 (95% CI 0.65-1.28, P = .60) for major bleeding.. No statistically significant difference in the risk of ISSE or major bleeding was found between rivaroxaban- and warfarin-treated patients. Although further study is needed, rivaroxaban appears to be a reasonable alternative to warfarin for ISSE prevention in the setting of NVAF and stage IV-V CKD.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Humans; Male; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Rivaroxaban; Severity of Illness Index; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Renal Insufficiency, Chronic; Rivaroxaban; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Renal Insufficiency, Chronic; Rivaroxaban; Warfarin

The comparative effectiveness of direct-acting oral anticoagulants, compared with warfarin, for risks of stroke/systemic embolism, major bleeding, or death have not been studied in Medicare beneficiaries with atrial fibrillation and nondialysis-dependent chronic kidney disease.. Medicare data from 2011 to 2017 were used to identify patients with stages 3, 4, or 5 chronic kidney disease and new atrial fibrillation who received a new prescription for warfarin, apixaban, rivaroxaban, or dabigatran. We estimated marginal hazard ratios with 95% CIs for the association of each direct-acting oral anticoagulant, compared with warfarin, for the outcomes of interest using inverse-probability-of-treatment weighted Cox proportional hazards models in as-treated and intention-to-treat analyses.. A total of 22 739 individuals met criteria (46.3% warfarin, 29.6% apixaban, 17.2% rivaroxaban, 6.9% dabigatran). Across the groups of anticoagulant users, mean age was 78.4 to 79.0 years; 50.3% to 51.4% were women, and 80.3% to 82.8% had stage 3 chronic kidney disease. In the as-treated analysis, for stroke/systemic embolism, hazard ratios, all compared with warfarin, were 0.70 (0.51-0.96) for apixaban, 0.80 (0.54-1.17) for rivaroxaban, and 1.15 (0.69-1.94) for dabigatran. For major bleeding, analogous hazard ratios were 0.47 (0.37-0.59) for apixaban, 1.05 (0.85-1.30) for rivaroxaban, and 0.95 (0.70-1.31) for dabigatran. There was no difference in the risk of all-cause mortality between the direct-acting oral anticoagulants and warfarin. Results of the intention-to-treat analysis were similar.. Apixaban, compared with warfarin, was associated with decreased risk of stroke/systemic embolism and major bleeding; risks for both outcomes with rivaroxaban and dabigatran did not differ from risks with warfarin.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Hemorrhage; Humans; Male; Medicare; Middle Aged; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Retrospective Studies; Stroke; United States; Warfarin; Young Adult

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Humans; Renal Insufficiency, Chronic; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Medicare; Renal Insufficiency, Chronic; United States; Warfarin

Topics: Aged; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Medicare; Renal Insufficiency, Chronic; United States; Warfarin

Atrial fibrillation (AF) is associated with increased stroke and bleeding risk in patients with chronic kidney disease (CKD). Little is known about the real-life use of non-vitamin K antagonist oral anticoagulants (NOACs) in CKD stage G4. In a retrospective cohort study, we enrolled 182 consecutive AF patients with CKD stage G4 including 90 (49%) subjects on NOAC, ie, 61 on apixaban 2.5 mg bid and 29 on rivaroxaban 15 mg qd, and 92 (51%) subjects on warfarin. Thromboembolic and bleeding events were recorded during a mean follow-up of 26.3 months. There were no differences in demographic, clinical, and laboratory variables at baseline between the 2 treatment groups. During follow-up, arterial thromboembolic events occurred in 11 (12.22%) subjects on NOAC and 7 (7.61%) on warfarin, (hazard ratio [HR] 1.70; 95% CI, 0.65-4.42), with similar risk of ischemic stroke (9 [10%] vs. 7 [7.61%], P = 0.56, respectively). Major bleedings or clinically relevant nonmajor bleeding occurred in 14 (15.56%) on NOAC and 13 (14.13%) on warfarin, (HR 1.12; 95% CI, 0.53-2.39), with similar risk of gastrointestinal bleeding (HR 0.70; 95% CI, 0.20-2.47). We observed no difference in all-cause mortality related to the type of anticoagulants, but it tended to be lower in the apixaban group compared with rivaroxaban group (14.7% vs. 31%, P = 0.07), without any differences in thromboembolic and bleeding events. The study suggests that AF patients with CKD stage G4 receiving reduced-dose NOAC or warfarin have similar risk of thromboembolism and bleeding in everyday practice of a tertiary anticoagulation center.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Poland; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Severity of Illness Index; Stroke; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

The aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of atrial fibrillation (AF) in patients with late-stage chronic kidney disease (CKD) who transitioned to dialysis.. The clinical benefit of warfarin therapy for thromboprophylaxis after incident AF diagnosis in patients with late-stage CKD who are transitioning to dialysis is unknown.. In this retrospective cohort analysis, the study population was a national cohort of 22,771 U.S. veterans with incident end-stage renal disease who developed incident AF before initiating renal replacement therapy. This study examined the association of warfarin therapy following the diagnosis of incident AF with ischemic cerebrovascular accidents (CVAs) (ischemic stroke or transient ischemic attack), ischemic CVA-related hospitalization, major bleeding events (gastrointestinal or intracranial bleeding), bleeding event-related hospitalizations, and post-dialysis, all-cause mortality in multivariable adjusted Cox regression analyses that adjusted for demographic characteristics and comorbidities.. The mean ± SD age of the cohort was 73.5 ± 8.8 years, 13% were African American, and the mean CHA. In patients with late-stage CKD who transitioned to dialysis, warfarin use was associated with higher risk of ischemic and bleeding events but a lower risk of mortality. Future studies such as those comparing warfarin with newer oral anticoagulant agents are needed to granularly define the net clinical benefit of anticoagulation therapy in patients with advanced CKD with incident AF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Humans; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Renal Insufficiency, Chronic; Stroke; Warfarin

Direct oral anticoagulants (DOACs) are effective alternatives to warfarin for stroke prevention in patients with atrial fibrillation (AF) including patients with CKD III. However, data on patient outcomes with DOACs for advanced CKD are limited, while warfarin use is controversial.. A retrospective study of patients with AF using DOACs and CKD stages III-V was conducted. The primary outcomes were stroke or systemic embolism and major bleeding while on DOAC therapy among CKD IV and V patients. Rates of outcomes from the DOAC trials and from previous studies of warfarin in CKD were referenced.. Of 316 patients reviewed, 152 were included with mean CrCl of 38.8 mL/min. Stroke and systemic embolism occurred at a rate of 1.17 per 100 person-years, with no significant difference between CKD IV/V and CKD III (P = .567). Rates were comparable to DOAC use from the DOAC trials, and lower than rates in studies of warfarin in CKD IV/V patients. There was a nonstatistically significant trend toward increased major bleeding in CKD IV/V patients. Rates of major bleeding in CKD III to V subjects were comparable to published rates for warfarin users with similar levels of renal impairment.. In our study, DOACs appeared to be as efficacious and safe in CKD IV and V as in CKD III. In addition, DOACs appeared to be more effective than, and as safe as warfarin when compared with reference studies of patients with advanced CKD. Our findings support the use of DOACs for thromboembolism prevention in patients with advanced CKD and AF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Renal Insufficiency, Chronic; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

Antithrombotic (AT) therapy has been known to increase post-endoscopic resection (ER) bleeding risk; however, there are few studies quantifying the effect of AT agents. This study aimed to analyze the incidence of delayed bleeding (DB) based on AT agents administered and to identify the proper timing of drug cessation.. Between January 2011 and March 2017, 7752 patients with 8242 lesions underwent ER for single gastric neoplasm. After a 2:1 propensity score matching using age, sex, specimen size, tumor location, diagnosis, chronic kidney disease, and liver cirrhosis, 798 and 399 lesions were classified as belonging to the matched control (MC) group and AT group, respectively. The clinical outcomes were compared between the 2 groups.. The DB rate of the MC and AT groups was 6.3% and 10.0%, respectively. There was no significant difference in the early DB rate between the 2 groups; however, the late DB rate of the AT group was higher than the MC group. The continuation group of the AT group had a higher incidence of DB than their matched control subjects (15.9% vs 5.1%; odds ratio, 3.55; 95% confidence interval, 1.24-10.14; P = .018). In patients taking anticoagulants, heparin bridging therapy (HBT) increased the incidence of DB compared with non-HBT (35.7% vs 10.0%; odds ratio, 5.00; 95% confidence interval, 1.11-22.50; P = .036). No thromboembolic events were observed in patients taking AT agents.. Patients receiving AT therapy had a higher incidence of DB than those not receiving AT therapy, especially with the continued administration of AT agents and HBT.

Topics: Aged; Anticoagulants; Antithrombins; Aspirin; Case-Control Studies; Deprescriptions; Endoscopic Mucosal Resection; Factor Xa Inhibitors; Female; Gastroscopy; Heparin; Humans; Incidence; Liver Cirrhosis; Logistic Models; Male; Middle Aged; Multivariate Analysis; Perioperative Care; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Propensity Score; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Stomach Neoplasms; Thromboembolism; Time Factors; Warfarin

Topics: Humans; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Warfarin

Topics: Humans; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Warfarin

Topics: Humans; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Warfarin

Patients with nonvalvular atrial fibrillation with stage 4 or 5 chronic kidney disease or undergoing hemodialysis were excluded from phase III randomized trials of nonvitamin K antagonist oral anticoagulants (NOACs). We sought to evaluate the effectiveness and safety of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation and stage 4 or 5 chronic kidney disease or undergoing hemodialysis in routine practice.. Using MarketScan data from January 2012 to December 2017, we identified patients on oral anticoagulant (OAC) with naïve nonvalvular atrial fibrillation and stage 4 or 5 chronic kidney disease or undergoing hemodialysis and with ≥12 months of insurance coverage before OAC initiation. Differences in baseline covariates between the rivaroxaban and warfarin cohorts were adjusted using inverse probability-of-treatment weights based on propensity scores calculated using generalized boosted models and 10,000 regression trees (absolute standardized differences <0.1 achieved for all covariates after adjustment). Patients were followed until a stroke/systemic embolism or major bleeding event, OAC discontinuation/switch, insurance disenrollment, or end of data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the OAC cohorts were calculated using Cox regression.. We identified 1896 rivaroxaban (38.7% received a dose <20 mg/d) and 4848 warfarin users. Eighty-eight percent of included patients had stage 5 chronic kidney disease or were undergoing hemodialysis. Rivaroxaban did not significantly reduce stroke or systemic embolism (HR = 0.55, 95% CI = 0.27-1.10) or ischemic stroke (HR = 0.67, 95% CI = 0.30-1.50) alone, but it was associated with a significant 32% (95% CI = 1-53%) reduction in major bleeding risk compared with warfarin.. Among patients with nonvalvular atrial fibrillation and stage 4 or 5 chronic kidney disease or undergoing hemodialysis, rivaroxaban appears associated with significantly less major bleeding compared to warfarin.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Databases, Factual; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Rivaroxaban; Stroke; United States; Warfarin; Young Adult

BACKGROUND Worldwide, the treatment of patients with chronic kidney disease (CKD) remains a challenge as warfarin treatment can be associated with severe adverse events related to bleeding. Alternative anticoagulants that can be used in CKD remain to be identified. This study aimed to compare the effects of indobufen, a new antiplatelet agent, with warfarin in a rat model of adenine-induced CKD. MATERIAL AND METHODS Forty-eight male Wistar rats were treated with intragastric adenine to create the rat model of CKD and were divided into four groups: an untreated control group (N=12), a group treated with dimethyl sulfoxide (DMSO) (N=12), a group treated with indobufen, (N=12) and a group treated with warfarin (N-12). Treatment was given for 4 weeks and 8 weeks. Kidney histology was performed, and the degree of fibrosis was quantified using Masson trichrome staining. RESULTS In the rat model of adenine-induced CKD, Masson trichrome staining showed that the degree of kidney fibrosis in the indobufen group (26%) was significantly reduced (p<0.05) when compared the DMSO group (58%) and the warfarin group (49%). Kidney fibrosis was associated with upregulation of 6-keto-PGI2/TXB2 in the rat kidney tissue. CONCLUSIONS In a rat model of adenine-induced CKD, preliminary findings showed that indobufen was associated with reduced kidney fibrosis when compared with warfarin.

Topics: Adenine; Animals; Anticoagulants; China; Disease Models, Animal; Fibrosis; Isoindoles; Kidney; Kidney Failure, Chronic; Male; Phenylbutyrates; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Renal Insufficiency, Chronic; Warfarin

Atrial fibrillation (AF) is increasingly prevalent in chronic kidney disease (CKD) patients. The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in AF and CKD patients remains unknown. This systematic review and meta-analysis will mainly assess net clinical benefit (NCB) property of NOACs versus warfarin in patients with AF and CKD by a pooled-analysis.. We will search Medline, Embase, Cochrane Library, and Clinical Trials.gov Website comprehensively for eligible randomized controlled trials that report the efficacy and safety outcomes according to renal function of NOACs. Relative risks and their 95% confidence intervals will be calculated using fixed- and random-effects models. Subgroup, sensitivity, and regression analyses will be performed to evaluate intertrial heterogeneity and bias of the results. NCB that balance stroke/systemic embolism (SSE) and major bleeding will be calculated using Singer's method.. This systemic review and meta-analysis will evaluate the NCB of NOACs versus warfarin via SSE, major bleeding and all-cause death in patients with CKD.. This study will provide new evidence for clinical profile of NOACs on SSE, major bleeding, all-cause death, and NCB in CKD patients.. CRD42019116940.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Meta-Analysis as Topic; Renal Insufficiency, Chronic; Research Design; Systematic Reviews as Topic; Warfarin

Topics: Anticoagulants; Humans; Renal Insufficiency, Chronic; Warfarin

The effect of uninterrupted oral anticoagulant use in patients with chronic kidney disease (CKD) during catheter ablation for atrial fibrillation (AF) is not fully understood.. The present study aimed to evaluate the safety and efficacy of periprocedural uninterrupted direct oral anticoagulant (DOAC) use compared with those of uninterrupted warfarin use in patients undergoing catheter ablation for AF stratified by various renal function groups.. A total of 2091 patients were retrospectively included in this study. The study population was divided into 4 groups: creatinine clearance level ≥80 mL/min (n = 1086), 50-79 mL/min (n = 774), 15-49 mL/min (n = 209), and <15 mL/min (n = 22). We investigated periprocedural complications and compared them between uninterrupted DOAC and warfarin groups.. There was no significant difference in thromboembolic events among the 4 groups (0.6%, 0.6%, 1.0%, and 0%, respectively; P = .792). However, major bleeding events (0.9%, 1.4%, 4.8%, and 4.5%; P < .001) and minor bleeding events (4.1%, 6.1%, 11.5%, and 13.6%; P < .001) primarily occurred in patients with CKD. The rate of periprocedural complications in the DOAC group was similar to that in the warfarin group for each renal function category. Adverse events did not differ after adjustment using propensity score-matched analysis. Multivariate analysis showed that lower body weight, antiplatelet drug use, initial ablation session, and CKD were independent predictors of adverse events.. The periprocedural bleeding risk was increased in patients with CKD. Uninterrupted DOAC and warfarin administration during catheter ablation for AF in patients with CKD is feasible and effective.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Female; Follow-Up Studies; Glomerular Filtration Rate; Hemorrhage; Humans; Incidence; Japan; Male; Middle Aged; Prognosis; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Stroke; Warfarin

Topics: Acute Kidney Injury; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Comorbidity; Female; Humans; Kidney Function Tests; Male; Renal Insufficiency, Chronic; Risk Adjustment; Risk Factors; Rivaroxaban; Stroke; Treatment Outcome; United States; Warfarin

To assess the association between anticoagulation, ischaemic stroke, gastrointestinal and cerebral haemorrhage, and all cause mortality in older people with atrial fibrillation and chronic kidney disease.. Propensity matched, population based, retrospective cohort analysis from January 2006 through December 2016.. The Royal College of General Practitioners Research and Surveillance Centre database population of almost 2.73 million patients from 110 general practices across England and Wales.. Patients aged 65 years and over with a new diagnosis of atrial fibrillation and estimated glomerular filtration rate (eGFR) of <50 mL/min/1.73m. Receipt of an anticoagulant prescription within 60 days of atrial fibrillation diagnosis.. Ischaemic stroke, cerebral or gastrointestinal haemorrhage, and all cause mortality.. 6977 patients with chronic kidney disease and newly diagnosed atrial fibrillation were identified, of whom 2434 were on anticoagulants within 60 days of diagnosis and 4543 were not. 2434 pairs were matched using propensity scores by exposure to anticoagulant or none and followed for a median of 506 days. The crude rates for ischaemic stroke and haemorrhage were 4.6 and 1.2 after taking anticoagulants and 1.5 and 0.4 in patients who were not taking anticoagulant per 100 person years, respectively. The hazard ratios for ischaemic stroke, haemorrhage, and all cause mortality for those on anticoagulants were 2.60 (95% confidence interval 2.00 to 3.38), 2.42 (1.44 to 4.05), and 0.82 (0.74 to 0.91) compared with those who received no anticoagulation.. Giving anticoagulants to older people with concomitant atrial fibrillation and chronic kidney disease was associated with an increased rate of ischaemic stroke and haemorrhage but a paradoxical lowered rate of all cause mortality. Careful consideration should be given before starting anticoagulants in older people with chronic kidney disease who develop atrial fibrillation. There remains an urgent need for adequately powered randomised trials in this population to explore these findings and to provide clarity on correct clinical management.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebral Hemorrhage; England; Female; Gastrointestinal Hemorrhage; Humans; Male; Renal Insufficiency, Chronic; Retrospective Studies; Stroke; Wales; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Renal Insufficiency, Chronic; Stroke; Warfarin

Chronic kidney disease (CKD) causes dysregulation of mineral metabolism, vascular calcification and renal osteodystrophy, an entity called 'CKD-Mineral and Bone Disorder' (CKD-MBD). Here we determine whether metformin, an anti-diabetic drug, exerts favorable effects on progressive, severe CKD and concomitant mineral metabolism disturbances. Rats with CKD-MBD, induced by a 0.25% adenine diet for eight weeks, were treated with 200 mg/kg/day metformin or vehicle from one week after CKD induction onward. Severe, stable CKD along with marked hyperphosphatemia and hypocalcemia developed in these rats which led to arterial calcification and high bone turnover disease. Metformin protected from development toward severe CKD. Metformin-treated rats did not develop hyperphosphatemia or hypocalcemia and this prevented the development of vascular calcification and inhibited the progression toward high bone turnover disease. Kidneys of the metformin group showed significantly less cellular infiltration, fibrosis and inflammation. To study a possible direct effect of metformin on the development of vascular calcification, independent of its effect on renal function, metformin (200 mg/kg/day) or vehicle was dosed for ten weeks to rats with warfarin-induced vascular calcification. The drug did not reduce aorta or small vessel calcification in this animal model. Thus, metformin protected against the development of severe CKD and preserved calcium phosphorus homeostasis. As a result of its beneficial impact on renal function, associated comorbidities such as vascular calcification and high bone turnover disease were also prevented.

Topics: Adenine; Animals; Chronic Kidney Disease-Mineral and Bone Disorder; Disease Models, Animal; Humans; Hypoglycemic Agents; Male; Metformin; Rats; Rats, Wistar; Renal Insufficiency, Chronic; Severity of Illness Index; Treatment Outcome; Vascular Calcification; Warfarin

Chronic kidney disease (CKD) aggravates course of practically all diseases by worsening outcomes and hindering adequate treatment. Specificities of renal excretion of various drugs, changes of parameters of their pharmacokinetics and pharmacodynamics, nephrotoxic effects of drugs, tactics of drug therapy in conditions of CKD, terminal stage of kidney failure and dialysis are in the focus of attention of internists. To a greatest degree difficulties of drug therapy in CKD and associated clinical states refer to the group of anticoagulants. Kidney diseases and related complications of anticoagulant therapy served as stimulus for search for new pharmacological approaches in anticoagulation, which resulted in creation and elaboration of novel oral anticoagulants (NOACs). NOACs are characterized by rapid onset and cessation of action, predictable pharmacokinetics, low potential of interaction with drugs and foods. Indicators of efficacy and safety of NOACs are similar to those of warfarin. Nevertheless, hemorrhagic and thrombotic events constitute the basis of further theoretical and practical investigations. These complications also stimulate aiming at selection of safest and balanced medicines. In this article we present various aspects of use of direct oral anticoagulants mostly in patients with CKD associated with atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Renal Insufficiency, Chronic; Stroke; Warfarin

Warfarin-related nephropathy (WRN) is a complication of warfarin over-anticoagulation that is associated with acute and/or chronic renal dysfunction and increased mortality. The long-term effects of warfarin on renal function has not been adequately studied in patients with a mechanical prosthetic valve (MPV).. To study the time-dependent effects of over-anticoagulation on renal function in patients with a MPV.. A total of 193 patients who underwent MPV implantation and were followed up in this study were eligible for inclusion. Time above therapeutic international normalized ratio (INR) range (TATR) was calculated by dividing the number of INR measurements above target in a year by the total number of INR measurements within a year. Patients were divided into quartiles according to average TATR at 60 months.. At 60 months more patients within the 4th quartile had a ≥20% reduction in the estimated glomerular filtration rate (eGFR, 25.0%, p = 0.04) and chronic kidney disease (CKD, 33.0%, p = 0.07) compared to patients within the 1st quartile. High TATR remained a significant determinant for reduction in eGFR (odds ratio OR: 7.50, 95% confidence interval CI:1.55-36.32) and CKD (OR:5.15, 95% CI: 1.26-20.62) after adjusting for other variables. Longitudinal analysis revealed that the change in eGFR was related to the duration of warfarin use (p < 0.001) and the interaction between the duration of warfarin use and TATR (p = 0.03). Similar findings were observed in patients without CKD at baseline, but not in those with CKD before the index operation.. Anticoagulation over targeted INR values is associated with a steeper decline in eGFR and an increased frequency of CKD in patients with a MPV.

Topics: Adult; Anticoagulants; Cohort Studies; Female; Glomerular Filtration Rate; Heart Valve Prosthesis; Humans; Male; Middle Aged; Prospective Studies; Renal Insufficiency, Chronic; Retrospective Studies; Warfarin

Because of a lack of comparative data on anticoagulant use in the advanced chronic kidney disease (CKD) population, guidelines recommend warfarin for atrial fibrillation and venous thromboembolism (VTE) treatment in these patients. However, apixaban has specific dosing recommendations in CKD leading to use in clinical practice.. To evaluate major bleeding, stroke, and thromboembolism rates in patients with CKD stage 4, stage 5, and dialysis on apixaban or warfarin therapy.. This was a retrospective cohort study of patients with advanced CKD receiving apixaban or warfarin. The primary outcome was the occurrence of major bleeding at 3 months after enrollment. Secondary outcomes included occurrence of major bleeding, occurrence of ischemic stroke, and recurrence of VTE at 3 to 6 and 6 to 12 months.. A total of 604 patients were included in the analysis. The percentage of apixaban and warfarin patients with a major bleed at 0 to 3, 3 to 6, and 6 to 12 months were 8.3% versus 9.9% ( P=0.48), 1.4% versus 4% ( P=0.07), and 1.5% versus 8.4% ( P<0.001), respectively. There were no differences in rates of ischemic stroke or recurrent VTE at any time period. Conclusion and Relevance: Patients with advanced CKD taking apixaban had similar bleeding rates at 3 months compared with those taking warfarin. However, those who continued therapy had higher major bleeding rates with warfarin between 6 and 12 months. This study provides knowledge on the effects of a direct oral anticoagulant in a population that was excluded from all major trials.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Treatment Outcome; Venous Thromboembolism; Warfarin

In chronic kidney disease (CKD) patients, the ratio of warfarin enantiomers is changed and becomes unstable due to a reduction of cytochrome P450 (CYP) 2C9 activity of, which contributes to the development of hemorrhagic complications. The aim of this study was to investigate the influence of interventions by clinical pharmacists in addition to guidance by physicians on time in therapeutic range (TTR) control of warfarin therapy for CKD patients with non-valvular atrial fibrillation (NVAF). This retrospective cohort study included NVAF patients with CKD admitted and discharged from a cardiovascular internal medicine ward between March 2011 and July 2013 in Yokosuka Kyousai Hospital. Participants were classified into two groups according to the instructions by clinical pharmacists and physicians (intervention group) and by physicians only (usual care group). The primary outcome was TTR. Secondary outcomes were major bleeding and minor bleeding. In total, 39 participants (28 males, 11 females; mean age: 72.1 years) were classified into the intervention (n = 16) and usual care (n = 23) groups. TTR in the intervention group was significantly higher than in the usual care group. Major bleeding and minor bleeding were not significantly different between the two groups. The intervention of clinical pharmacists with anticoagulation therapy can lead to a proper use of warfarin prescribed by physicians.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Cytochrome P-450 CYP2C9; Female; Hemorrhage; Humans; Male; Pharmaceutical Services; Pharmacists; Professional Role; Renal Insufficiency, Chronic; Retrospective Studies; Warfarin

In recent years, novel anticoagulant drugs have been introduced in the clinical armamentarium and have progressively gained momentum. Although their use is increasing among CKD patients, some skepticism about their risk-benefit ratio still persists. We sought to investigate the safety and effectiveness of rivaroxaban in a cohort of moderate-to-advanced CKD patients.. This observational, retrospective, longitudinal study involved 347 consecutive CKD stage 3b-4 (according to NKF-KDOQI guidelines) patients enrolled from 8 cardiac outpatient clinics between March 2015 and October 2017. All patients received anticoagulation (100 warfarin vs. 247 rivaroxaban) as part of their non-valvular atrial fibrillation management at the attending physician's discretion. Clinical effectiveness (defined as the occurrence of ischemic stroke, venous thromboembolism, or transient ischemic attack) and safety (intracranial hemorrhage, gastrointestinal or other bleeding) were assessed separately.. Over a mean follow-up period of 16 ± 0.3 months, 25 stroke episodes (15 hemorrhagic, and 10 ischemic) occurred in 24 warfarin treated patients vs. none in the rivaroxaban arm. There were 5 vs. 0 episodes of deep venous thrombosis and 8 vs. 2 major episodes of bleeding in the warfarin and rivaroxaban groups, respectively. In contrast, the proportion of minor episodes of bleeding was similar between groups.. Rivaroxaban seems a safe and effective therapeutic option in CKD stage 3b-4 patients. However, future randomized controlled trials are needed to definitively establish the role of rivaroxaban in CKD patients.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Italy; Longitudinal Studies; Male; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Warfarin

Background Chronic kidney disease ( CKD ) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow-up data were included (N=9019). CKD was defined as an estimated creatinine clearance <60 mL /min. Patient characteristics were compared by CKD status, and Cox proportional hazards modeling was used to examine the association between oral anticoagulant ( OAC ) use and outcomes and antiarrhythmic drug use and outcomes stratified by CKD stages. At enrollment, 3490 (39%) patients had an estimated creatinine clearance <60 mL /min. Patients with CKD were older and had higher CHA

Topics: Administration, Oral; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Dabigatran; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Registries; Renal Insufficiency, Chronic; Risk Factors; Stroke; Time Factors; Treatment Outcome; Warfarin

Warfarin use for stroke prevention in atrial fibrillation (AF) patients with chronic kidney disease is debated. Apixaban was shown to be safer than warfarin, with superior reduction in the risk of stroke, systemic embolism, mortality, and major bleeding irrespective of kidney function.. To evaluate the cost-utility of apixaban compared with warfarin in AF patients at different levels of kidney function.. A Markov model was used to estimate the cost effectiveness of apixaban compared with warfarin in AF patients at three levels of kidney function: estimated glomerular filtration rate (eGFR) of more than 80 ml/min, 50 to 80 ml/min, and 50 ml/min or less. Event rates and associated utilities were obtained from previous literature. The model adopted the US health care system perspective, with hospitalization costs extracted from the Healthcare and Utilization Project. Treatment costs were obtained from official price lists. Univariate and probabilistic sensitivity analyses were performed to evaluate the robustness of results.. Apixaban was a dominant treatment strategy compared with warfarin in AF patients with eGFR levels of 50 ml/min or less and 50 to 80 ml/min. In patients with an eGFR of more than 80 ml/min, apixaban was cost-effective compared with warfarin, costing $6307 per quality-adjusted life-year gained. Results were consistent assuming anticoagulant discontinuation after major bleeding events. Compared with dabigatran and rivaroxaban, apixaban was the only cost-effective anticoagulant strategy relative to warfarin in both mild and moderate renal impairment settings.. Apixaban is a favorably cost-effective alternative to warfarin in AF patients with normal kidney function and potentially cost-saving in those with renal impairment.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cost-Benefit Analysis; Factor Xa Inhibitors; Fibrinolytic Agents; Glomerular Filtration Rate; Health Care Costs; Heart; Hospitalization; Humans; Kidney; Middle Aged; Pyrazoles; Pyridones; Quality of Life; Quality-Adjusted Life Years; Renal Insufficiency, Chronic; Stroke; Treatment Outcome; Warfarin

Chronic kidney disease (CKD) aggravates course of practically all diseases by worsening outcomes and hindering adequate treatment. Specificities of renal excretion of various drugs, changes of parameters of their pharmacokinetics and pharmacodynamics, nephrotoxic effects of drugs, tactics of drug therapy in conditions of CKD, terminal stage of kidney failure and dialysis are in the focus of attention of internists. To a greatest degree difficulties of drug therapy in CKD and associated clinical states refer to the group of anticoagulants. Kidney diseases and related complications of anticoagulant therapy served as stimulus for search for new pharmacological approaches in anticoagulation, which resulted in creation and elaboration of novel oral anticoagulants (NOACs). NOACs are characterized by rapid onset and cessation of action, predictable pharmacokinetics, low potential of interaction with drugs and foods. Indicators of efficacy and safety of NOACs are similar to those of warfarin. Nevertheless, hemorrhagic and thrombotic events constitute the basis of further theoretical and practical investigations. These complications also stimulate aiming at selection of safest and balanced medicines. In this article we present various aspects of use of direct oral anticoagulants mostly in patients with CKD associated with atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Renal Insufficiency, Chronic; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; International Normalized Ratio; Renal Insufficiency, Chronic; Risk Factors; Stroke; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; International Normalized Ratio; Renal Insufficiency, Chronic; Risk Factors; Stroke; Warfarin

Aspirin increases the risk of gastrointestinal bleeding.. To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.. Low-dose (75-325 mg daily) aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers.. A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio [HR]: 2.75, 95% confidence interval [CI]: 2.06-3.65), NSAIDs (HR: 8.61, 95% CI: 3.28-22.58), steroids (HR: 10.50, 95% CI: 1.98-55.57), SSRIs (HR: 11.71, 95% CI: 1.40-97.94), PPIs (HR: 8.47, 95% CI: 2.26-31.71), and H2RAs (HR: 10.83, 95% CI: 2.98-39.33) were significantly associated with LGIB.. The risk of LGIB was higher in low-dose aspirin users than in aspirin nonusers in this nationwide cohort. Low-dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Case-Control Studies; Clopidogrel; Comorbidity; Cyclooxygenase 2 Inhibitors; Databases, Factual; Dose-Response Relationship, Drug; Female; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Incidence; Male; Middle Aged; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors; Renal Insufficiency, Chronic; Risk Factors; Selective Serotonin Reuptake Inhibitors; Taiwan; Ticlopidine; Warfarin; Young Adult

Topics: Anticoagulants; Atrial Fibrillation; Humans; Renal Insufficiency, Chronic; Stroke; Warfarin

The anticoagulant effect of warfarin used to treat stroke has been shown to vary with the concomitant use of medications and comorbidity. Concomitant use of antithrombotic drugs and underlying chronic kidney disease (CKD) represent risk factors for bleeding events. We conducted a comprehensive investigation of the background characteristics and concomitant use of drugs to identify the risk factors for warfarin-related bleeding, focusing on renal function.. The study population consisted of patients prescribed warfarin at the Tokyo Women's Medical University Hospital. A retrospective review of the patient data, including bleeding events, bleeding sites, the patient's background, concomitant use of drugs, and laboratory data was carried out, and the incidence of bleeding events was compared in patient groups stratified according to CKD stage and antithrombotic drug use. Multivariate logistic regression analysis was performed to determine the risk factors for warfarin-related bleeding.. Of the 3,831 patients included in the study, the incidence of warfarin-related bleeding was 3.0 events per 100 patient-years. The multivariate logistic regression analysis identified age > 65 years, body mass index (BMI), alanine aminotransferase (ALT), estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m. The present analyses identified age > 65 years, BMI, ALT, eGFR <30 mL/min/1.73 m

Topics: Aged; Alanine Transaminase; Anticoagulants; Body Mass Index; Female; Fibrinolytic Agents; Glomerular Filtration Rate; Hemorrhage; Humans; International Normalized Ratio; Kidney; Male; Middle Aged; Prothrombin Time; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Renal Insufficiency, Chronic; Stroke; Warfarin

Relationships between the number of anti-thrombosis agents, clinical benefits and adverse events in hemodialysis (HD) patients are unclear.. All patients on HD in 22 institutes (n = 1,071) were enrolled and followed up for 3 years. After exclusion of patients with missing data, kidney transplantation or retraction of consent during the follow-up period (n = 204), mortality rate and ischemic and hemorrhagic events were compared between different regimens of anti-thrombosis agents.. The use of dual or triple antiplatelet (AP) agents (HR:2.03, 95% CI:1.01-4.13, p = 0.04) and the combination of an AP agent and warfarin (WF) (HR:4.84, 95%CI 1.96-11.96, p < 0.001) were associated with an increase in hemorrhagic events compared with no use of anti-thrombosis agents. No anti-thrombosis regimen was associated with a significant change in risk of ischemic stroke. The use of dual or triple AP agents, but not WF, was associated with an increase in cardiovascular mortality (HR:2.48, 95% CI:1.24-4.76, p = 0.01).. A significant increase in hemorrhagic events by the use of dual or more AP agents and by co-administration of an AP agent and WF in patients on HD should be considered in planning their anti-thrombosis regimen.

Topics: Aged; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Warfarin

Management of acute venous thromboembolism (VTE) with anticoagulants in elderly patients and those with chronic kidney disease poses special challenges. The RE-COVER and RE-COVER II trials showed that dabigatran 150 mg twice daily was as effective as warfarin over 6 months in preventing recurrent VTE, with a lower bleeding risk. We now assess the effects of old age and renal impairment (RI) on pooled trial outcomes in 5,107 patients: 4,504 aged <75 years and 603 aged ≥75 years. The primary efficacy outcome was symptomatic VTE/VTE-related death. Safety outcomes were centrally adjudicated major bleeding events (MBEs), MBEs or clinically relevant non-major bleeding events (MBEs/CRBEs) and any bleeds. Baseline renal function was categorized as normal, mild RI or moderate RI. A total of 3,698 had normal renal function and 1,100 and 237 had mild and moderate RI, respectively (23 patients with severe RI and 49 with missing creatinine clearance data were not included). For dabigatran, VTE/VTE-related death decreased from 3.1% (normal renal function) to 1.9% for mild RI and to 0.0% for moderate RI. For warfarin, the event rates were 2.6, 1.6 and 4.1%, respectively. Overall, major bleeding increased with increasing RI (

Topics: Acute Disease; Adult; Age Factors; Aged; Aging; Anticoagulants; Antithrombins; Clinical Trials, Phase III as Topic; Dabigatran; Female; Hemorrhage; Humans; Kidney; Male; Middle Aged; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Risk Factors; Time Factors; Treatment Outcome; Venous Thromboembolism; Warfarin

To evaluate warfarin prescription, quality of international normalised ratio (INR) monitoring and of INR control in patients with atrial fibrillation (AF) and chronic kidney disease (CKD).. We performed a retrospective cohort study of patients with newly diagnosed AF in the Veterans Administration (VA) healthcare system. We evaluated anticoagulation prescription, INR monitoring intensity and time in and outside INR therapeutic range (TTR) stratified by CKD.. Of 123 188 patients with newly diagnosed AF, use of warfarin decreased with increasing severity of CKD (57.2%-46.4%), although it was higher among patients on dialysis (62.3%). Although INR monitoring intensity was similar across CKD strata, the proportion with TTR≥60% decreased with CKD severity, with only 21% of patients on dialysis achieving TTR≥60%. After multivariate adjustment, the magnitude of TTR reduction increased with CKD severity. Patients on dialysis had the highest time markedly out of range with INR <1.5 or >3.5 (30%); 12% of INR time was >3.5, and low TTR persisted for up to 3 years.. There is a wide variation in anticoagulation prescription based on CKD severity. Patients with moderate-to-severe CKD, including dialysis, have substantially reduced TTR, despite comparable INR monitoring intensity. These findings have implications for more intensive warfarin management strategies in CKD or alternative therapies such as direct oral anticoagulants.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; Stroke; Time Factors; Treatment Outcome; Warfarin

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Renal Insufficiency, Chronic; Warfarin

The purpose of this study is to assess incidence and risk factors for severe renal dysfunction in patients requiring oral anticoagulation to help guide initial drug choice and provide a rational basis for interval monitoring of renal function for patients prescribed non-vitamin K oral anticoagulants.. Patients on warfarin for atrial fibrillation or venous thromboembolism were consecutively enrolled from January 2007 to December 2010. Baseline kidney function was assessed, and patients were followed to their first decline of kidney function to creatinine clearance<30 mL/min. Multivariate regression assessed independent risk factors for the primary outcome. Severe renal impairment based on baseline kidney function was assessed by Kaplan-Meier analyses.. Of 787 patients identified, 34 were excluded for baseline CrCl <30 mL/min. The mean age was 71 years, and 74% and 31% had hypertension and diabetes mellitus, respectively. At baseline, 23% (n=174) had moderate chronic kidney disease (CKD) (CrCl 30-59mL/min), whereas 31% had mild CKD (CrCl 60-89mL/min). Severe renal impairment occurred in 92 patients (12%), 25% of which was seen within 5.3 months. Of those with baseline stage 3 CKD, 37% developed severe renal impairment. Stage 3 CKD conferred a 14-fold increased risk in the development of severe renal dysfunction (odds ratio 14.5, 95% CI 6.7-31.3, P<.001). Coronary artery disease was also associated with severe renal impairment (odds ratio 2.2, 95% CI 1.3-3.8, P=.004).. Acute and chronic renal dysfunction is common among individuals requiring long-term anticoagulant therapy. Patients with moderate chronic kidney disease and coronary artery disease are at the highest short-term risk of developing severe renal impairment. More frequent monitoring of these patients is warranted.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Creatinine; Female; Humans; Incidence; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Renal Insufficiency, Chronic; Risk Factors; Severity of Illness Index; Stroke; Warfarin

It is unknown whether renal dysfunction conveys poor anticoagulation control in warfarin-treated patients with atrial fibrillation and whether poor anticoagulation control associates with the risk of adverse outcomes in these patients.. Severe chronic kidney disease (eGFR <30) patients with atrial fibrillation have worse INR control while on warfarin. An optimal TTR (>75%) is associated with lower risk of adverse events, independently of underlying renal function.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Creatinine; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Middle Aged; Odds Ratio; Prognosis; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Survival Rate; Sweden; Time Factors; Treatment Outcome; Warfarin

Little is known about the ischaemic stroke risk and benefit of warfarin therapy for stroke prevention in chronic kidney disease (CKD) patients on peritoneal dialysis (PD) with concomitant atrial fibrillation (AF). Our objective was to determine the risk of ischaemic stroke in a 'real-world' cohort of PD patients with AF, and clinical benefit or harm of aspirin and warfarin.. This is a single-centred observational study of Chinese patients with non-valvular AF. Hospitalizations with ischaemic stroke and intracranial haemorrhage (ICH) were recorded. Of 9810 patients from a hospital-based AF registry, 271 CKD patients on PD with AF (76.8 ± 12.5 years, CHA2DS2-VASc: 3.69 ± 1.83, and HAS-BLED: 2.07 ± 0.97) were identified. Amongst these PD patients, 24.7% received warfarin; 31.7% received aspirin; and 43.5% received no antithrombotic therapy. Amongst patients with no antithrombotic therapy, annual incidence of ischaemic stroke in PD patients was comparable with those non-CKD counterparts (9.32 vs. 9.30%/year). Similar to non-CKD patients, annual incidence of ischaemic stroke increased with increasing CHA2DS2-VASc score (CHA2DS2-VASc = 0-1: 5.76 vs. 5.70%/year, P = 1.00; and CHA2DS2-VASc ≥ 2: 10.80 vs. 9.94%/year, P = 0.78). Amongst PD patients, warfarin therapy was associated with lower risk of ischaemic stroke compared with aspirin [Hazard ratio (HR): 0.16, 95% confidence interval (CI): 0.04-0.66, P = 0.01] and no therapy (HR: 0.19, 95% CI: 0.06-0.65, P = 0.01), but not associated with a higher risk of ICH.. In CKD patients on PD with AF, who had similar ischaemic stroke risk as non-CKD counterparts, warfarin therapy is associated with reduction in risk of ischaemic stroke without a higher risk of ICH.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Hong Kong; Hospitalization; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Peritoneal Dialysis; Proportional Hazards Models; Registries; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Stroke; Warfarin

Clinical characteristics, management, and outcomes in hemodialysis patients with atrial fibrillation (AF) remain unclear.. We studied 423 Japanese patients undergoing maintenance hemodialysis (age 65.2±12.4 years, male 70%, mean duration of hemodialysis 139±124 months). AF was present in 19% (n=82) and was independently related to increased age (odds ratio 1.070, 95% confidence interval 1.043-1.098), longer hemodialysis duration (odds ratio 1.006, 95% confidence interval 1.004-1.008), and congestive heart failure (odds ratio 2.749, 95% confidence interval 1.546-4.891). During observations lasting a mean of 36 months, the incidences of all-cause death, cardiovascular death, and major bleeding, in particular gastrointestinal bleeding, were significantly higher in the AF (n=82) than the non-AF (n=341) patients (p<0.001, p=0.004, p=0.002, p=0.027, respectively), but the incidence of ischemic stroke/systemic embolism was similar in the AF and non-AF patients. AF was independently associated with all-cause death (hazard ratio 1.728, 95% confidence interval 1.123-2.660) and major bleeding (hazard ratio 1.984, 95% confidence interval 1.010-3.896). Warfarin was prescribed in 33% of the AF patients, but the rates of all-cause death, ischemic stroke, and major bleeding during the study period were not significantly different between warfarin (n=27) and non-warfarin (n=55) groups.. In our hemodialysis patients, AF was a common comorbidity and was independently associated with all-cause death and major bleeding, but not with increased risk of ischemic stroke.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cause of Death; Embolism; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Japan; Male; Middle Aged; Proportional Hazards Models; Registries; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Stroke; Time Factors; Warfarin

We conducted a multicenter prospective cohort study to assess the safety of warfarin therapy in Japanese hemodialysis (HD) patients.. Chronic HD patients on warfarin therapy (warfarin users) were recruited from 111 HD centers in Japan. Two dialysis-vintage-matched warfarin non-users (non-users) were selected from the same HD center as each warfarin user. Clinical data were collected upon registration and every 12 months thereafter for up to 36 months.. The final cohort consisted of 365 warfarin users and 692 non-users and was followed for an average of 27.7 months. The mean age of warfarin users (68.8 ± 10.6 years) was significantly higher than that of non-users (66.9 ± 11.0 years, p < 0.001). The analyses by multivariate Cox proportional-hazard models showed that the age [hazard ratio (HR) = 1.07 for each 1-year increase, 95 % confidence interval (CI) 1.05-1.08, p < 0.001] was significantly associated with the death from any cause, but warfarin use (1.08, CI 0.75-1.57, p = 0.68) was not when being adjusted for sex, diabetes mellitus, antiplatelet use, and atrial fibrillation. The risk of composite events, which included death from any cause, stroke, cardiovascular disease, and peripheral arterial disease, was also associated with age but was not associated with warfarin use.. The results of this study suggested that warfarin use by HD patients might not be harmful in chronic state, while the safety for the initiation of warfarin therapy in HD patients remained to be determined.

Topics: Age Factors; Aged; Anticoagulants; Calciphylaxis; Chi-Square Distribution; Female; Hemorrhage; Humans; Male; Middle Aged; Multivariate Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Stroke; Time Factors; Tokyo; Treatment Outcome; Warfarin

The novel oral anticoagulants, including dabigatran and rivaroxaban, differ in their degree of renal excretion.. We conducted a population-based nested case-control study in patients 66 years and older with chronic kidney disease (CKD) (excluding patients undergoing chronic dialysis) who received an oral anticoagulant between April 2006 and March 2013. We calculated odds ratios for hospitalization with a major hemorrhagic event and receipt of dabigatran, rivaroxaban, or warfarin in the preceding 60 days. We also performed a sensitivity analysis to investigate whether a relationship exists between major hemorrhage and advanced age (age < 80 years or ≥ 80 years).. We identified 237,409 patients with CKD, 4470 (1.9%) of whom experienced a major hemorrhage. We matched these patients to 14,460 controls. The use of dabigatran or rivaroxaban was not associated with a statistically significant elevated risk of hemorrhage compared with warfarin (adjusted odds ratio [aOR], 1.15; 95% confidence interval [CI], 0.91-1.45 for dabigatran; aOR, 1.22; 95% CI, 0.83-1.79 for rivaroxaban). Our sensitivity analysis found that older age was associated with an increased risk of hemorrhage for patients receiving dabigatran (aOR, 1.41; 95% CI, 1.06-1.88); results were similar but did not reach statistical significance for rivaroxaban (aOR, 1.57; 95% CI, 0.91-2.69).. Among elderly patients with CKD, exposure to dabigatran or rivaroxaban was not associated with a statistically significant increased risk of major hemorrhagic events compared with exposure to warfarin.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Dabigatran; Female; Hemorrhage; Humans; Male; Ontario; Renal Insufficiency, Chronic; Risk; Rivaroxaban; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Renal Insufficiency, Chronic; Risk; Risk Factors; Stroke; Warfarin

A 73-year-old man with chronic kidney disease stage G5 was admitted to our hospital because of a worsening kidney dysfunction. He had undergone prosthetic valve replacement of the mitral valve 5 years previously and was currently taking warfarin. He showed excessive anticoagulation on admission, with a prothrombin time-international normalized ratio (PT-INR) of 3.91. The use of warfarin was ceased and PT-INR decreased to 2.1. Since the patient would need renal replacement therapy, he underwent arteriovenous fistula surgery for hemodialysis access on day 16. However, on day 18, he suddenly complained of lumbago and went into shock. His blood pressure dropped to 73/49 mmHg, and the hemoglobin level fell to 4.9 g/dL. Computed tomography revealed a huge retroperitoneal hematoma. Emergent lumbar artery embolization was performed on two consecutive days; however, the bleeding persisted, with subsequent development of abdominal compartment syndrome with impaired respiratory and cardiovascular function, and the patient died. Autopsy revealed a hematoma measuring 30×20×20 cm involving the psoas muscle and external iliac artery; the hematoma was covered with fibrous tissue instead of muscle. The psoas muscle is supplied by the internal iliac artery; however, a collapsed artery could not be confirmed in our patient. The closest major artery to the hematoma was located at the intersection of the psoas muscle and the external iliac artery. All arteries showed severe atherosclerosis. In patients with advanced chronic kidney disease, anticoagulant therapy should be administered carefully, and the etiology of retroperitoneal hematoma should be further investigated.

Topics: Aged; Anticoagulants; Arteriovenous Shunt, Surgical; Autopsy; Embolization, Therapeutic; Fatal Outcome; Hematoma; Humans; Iliac Artery; International Normalized Ratio; Male; Prothrombin Time; Renal Dialysis; Renal Insufficiency, Chronic; Retroperitoneal Space; Tomography, X-Ray Computed; Warfarin

Chronic kidney disease (CKD) is highly prevalent in atrial fibrillation (AF) patients and associated with an increased risk of adverse outcomes. Our objectives were to study clinical features associated with CKD in AF patients and the impact of CKD on anticoagulation control, as reflected by time in therapeutic range (TTR). We also determined the impact of CKD and TTR in predicting adverse outcomes.. We analysed pooled datasets from SPORTIF III and V trials, including 3646 patients assigned to warfarin with data on renal function. CKD (creatinine clearance <60ml/min) was present in 952 (26%) patients. TTR was higher in patients with normal renal function compared to those with CKD (p<0.001). On logistic analysis, chronic AF and male sex were associated with TTR>70%, whilst diabetes mellitus, aspirin use and CKD were inversely associated with TTR>70%. On Cox regression analysis, CKD was an independent predictor for stroke (p=0.006) and death (p<0.001). TTR>70% was independently associated with a lower risk of stroke (p=0.024), death (p=0.001) and major bleeding (p=0.001).. CKD is highly prevalent amongst AF patients and a risk factor for stroke and death. Adjusting for CKD, good quality anticoagulation control (TTR>70%) was an independent predictor for lower risks of stroke, death and major bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Clinical Trials as Topic; Comorbidity; Female; Humans; Kidney Function Tests; Male; Middle Aged; Odds Ratio; Patient Outcome Assessment; Prevalence; Renal Insufficiency, Chronic; Thromboembolism; Warfarin

Warfarin therapy for stroke prevention is recommended for patients with AF, but its value in patients with chronic kidney disease on HD is unknown.. The anticoagulation regimens of patients with a prior history of AF hospitalized for initiation of chronic HD, and of patients receiving chronic HD who had a new diagnosis of AF between 2009 and 2012 were reviewed. Exclusions were renal transplant, peritoneal dialysis, rheumatic valve disease, prosthetic heart valve, GI bleeding, malignancy with chemotherapy in last 6months or still undergoing treatment, a history of AF ablation, a history of ICD implantation, or those receiving warfarin for non-AF indications.. Among 302 patients included in the study, 119 (39%) were prescribed warfarin and 183 (61%) were not. The two groups were similar regarding demographics, and prevalence of comorbidities including diabetes, heart failure, coronary artery disease, hypertension, use of antiplatelet agents and prior stroke. Warfarin use did not lower risk for ischemic stroke (HR 0.93; 95% CI 0.49-1.82, P=0.88) or improve overall survival (HR 1.02; 95% CI 0.91-1.15, P=0.62), but trended toward higher risk of bleeding complications (HR 1.53; 95% CI 0.94-2.51, P=0.086) after adjusting for potential confounders.. Warfarin use was not associated with reduction in stroke risk or mortality in patients with AF on chronic HD, but trended toward greater bleeding risk. The benefit of warfarin therapy in these patients may be outweighed by its risks.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comorbidity; Female; Hemorrhage; Humans; Male; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Stroke; Survival Analysis; United States; Warfarin

Topics: Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Chest Pain; Coronary Artery Disease; Drug-Eluting Stents; Fibrinolytic Agents; Heart Failure; Humans; Hypertension; Male; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic; Tachycardia, Ventricular; Treatment Outcome; Warfarin

Hypertension is a common comorbidity in patients with chronic kidney disease (CKD). We reported earlier that oral anticoagulants, including warfarin and dabigatran, may induce acute kidney injury. No effects of oral anticoagulants on blood pressure (BP) have been previously reported. The aim of this study was to examine in detail the relationship of anticoagulant therapy and BP in rats.. Sham-operated and 5/6 nephrectomy rats were treated with different doses of oral anticoagulants (warfarin and dabigatran), superoxide scavenger N-acetylcysteine (NAC), vitamin K, and protease activated receptor 1 (PAR-1) inhibitor SCH79797. BP was measured by a tail cuff daily.. Warfarin and dabigatran both increased systolic BP in sham-operated and 5/6 nephrectomy rats in a dose-dependent manner. SCH79797 also increased systolic BP in a dose-dependent manner. Vitamin K prevented warfarin-induced increase in BP but did not affect BP when administered alone. NAC delayed the warfarin-associated increase in BP. Warfarin effects on BP were similar in 5/6 nephrectomy rats with different CKD stages.. Both warfarin and dabigatran increase systolic BP in rats. The mechanism of this effect is not clear, but our data suggest that it is related to decreased thrombin activity associated with anticoagulant treatment. The superoxide scavenger NAC delayed, but did not prevent, warfarin-induced hypertension.

Topics: Acetylcysteine; Animals; Anticoagulants; Antifibrinolytic Agents; Antithrombins; Benzimidazoles; beta-Alanine; Blood Pressure; Dabigatran; Disease Models, Animal; Dose-Response Relationship, Drug; Free Radical Scavengers; Nephrectomy; Pyrroles; Quinazolines; Rats; Receptor, PAR-1; Renal Insufficiency, Chronic; Vitamin K; Warfarin

Topics: Blood Coagulation Disorders; Echocardiography, Transesophageal; Electrocardiography; Female; Follow-Up Studies; Heart Diseases; Humans; Magnetic Resonance Imaging, Cine; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Severity of Illness Index; Thrombosis; Treatment Outcome; Warfarin

Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated 'real-world' information on how these drugs are being adopted.. Using Danish nationwide administrative registers, we identified all oral anticoagulation-naïve AF patients initiating oral anticoagulation from 22 August 2011 through 31 October 2013. Using logistic regression analysis, baseline characteristics and temporal utilization trends were compared between initiators of warfarin vs. one of the N OACs: dabigatran, rivaroxaban, or apixaban. We identified 18 611 oral anticoagulation-naïve AF patients of which 9902 (53%) initiated warfarin treatment, 7128 (38%) dabigatran, 1303 (7%) rivaroxaban, and 278 (1%) apixaban. Overall, 40% of newly initiated patients were started on dabigatran within the first 4 months of when the drug came on market. By October, 2013, 40% were being started on warfarin and dabigatran, respectively, and another 20% were started on either rivaroxaban or apixaban. Rivaroxaban and apixaban users generally had a higher predicted risk of stroke and bleeding compared with warfarin and dabigatran users. Older age, female gender, and prior stroke were some of the factors associated with NOAC use vs. warfarin, whereas chronic kidney disease, myocardial infarction, and heart failure showed the opposite association.. Among oral anticoagulation-naïve AF patients initiated on oral anticoagulation in Denmark, warfarin initiation has declined since the introduction of dabigatran in August 2011. Dabigatran is the most frequently used alternative option to warfarin; however, use of rivaroxaban and apixaban is increasing. Patients initiated with rivaroxaban or apixaban in general have a higher predicted stroke and bleeding risks compared with warfarin or dabigatran initiators.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Comorbidity; Dabigatran; Denmark; Female; Heart Failure; Humans; Male; Middle Aged; Morpholines; Myocardial Infarction; Myocardial Ischemia; Practice Patterns, Physicians'; Pyrazoles; Pyridones; Registries; Renal Insufficiency, Chronic; Rivaroxaban; Sex Factors; Stroke; Thiophenes; Warfarin

Topics: Anticoagulants; Diet; Drug Monitoring; Food; Humans; International Normalized Ratio; Potassium; Prothrombin; Renal Insufficiency, Chronic; Vitamin K; Warfarin

To determine rates of major bleeding by level of kidney function for older adults with atrial fibrillation starting warfarin.. Retrospective cohort study.. Community based, using province wide laboratory and administrative data in Alberta, Canada.. 12,403 adults aged 66 years or more, with atrial fibrillation who started warfarin treatment between 1 May 2003 and 31 March 2010 and had a measure of kidney function at baseline. Kidney function was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation and participants were categorised based on estimated glomerular filtration rate (eGFR): ≥ 90, 60-89, 45-59, 30-44, 15-29, <15 mL/min/1.73 m(2). We excluded participants with end stage renal disease (dialysis or renal transplant) at baseline.. Admission to hospital or visit to an emergency department for major bleeding (intracranial, upper and lower gastrointestinal, or other).. Of 12,403 participants, 45% had an eGFR <60 mL/min/1.73 m(2). Overall, 1443 (11.6%) experienced a major bleeding episode over a median follow-up of 2.1 (interquartile range: 1.0-3.8) years. During the first 30 days of warfarin treatment, unadjusted and adjusted rates of major bleeding were higher at lower eGFR (P for trend <0.001 and 0.001, respectively). Adjusted bleeding rates per 100 person years were 63.4 (95% confidence interval 24.9 to 161.6) in participants with eGFR <15 mL/min/1.73 m(2) compared with 6.1 (1.9 to 19.4) among those with eGFR >90 mL/min/1.73 m(2) (adjusted incidence rate ratio 10.3, 95% confidence interval 2.3 to 45.5). Similar associations were observed at more than 30 days after starting warfarin, although the magnitude of the increase in rates across eGFR categories was attenuated. Across all eGFR categories, adjusted rates of major bleeding were consistently higher during the first 30 days of warfarin treatment compared with the remainder of follow-up. Increases in major bleeding rates were largely due to gastrointestinal bleeding (3.5-fold greater in eGFR <15 mL/min/1.73 m(2) compared with ≥ 90 mL/min/1.73 m(2)). Intracranial bleeding was not increased with worsening kidney function.. Reduced kidney function was associated with an increased risk of major bleeding among older adults with atrial fibrillation starting warfarin; excess risks from reduced eGFR were most pronounced during the first 30 days of treatment. Our results support the need for careful consideration of the bleeding risk relative to kidney function when assessing the risk-benefit ratio of warfarin treatment in people with chronic kidney disease and atrial fibrillation, particularly in the first 30 days of treatment.

Topics: Aged; Aged, 80 and over; Alberta; Anticoagulants; Atrial Fibrillation; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Incidence; Male; Regression Analysis; Renal Insufficiency, Chronic; Retrospective Studies; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Renal Insufficiency, Chronic; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Renal Insufficiency, Chronic; Warfarin

Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor, thereby attenuating the differential effect by race. Attenuation likely occurs in both race groups but may be more pronounced in the less-represented race group. Therefore, we evaluated whether the effect of clinical (age, body surface area [BSA], chronic kidney disease [CKD], and amiodarone use) and genetic factors (CYP2C9*2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F2) on warfarin dose differs by race using regression analyses among 1357 patients enrolled in a prospective cohort study and compared predictive ability of race-combined vs race-stratified models. Differential effect of predictors by race was assessed using predictor-race interactions in race-combined analyses. Warfarin dose was influenced by age, BSA, CKD, amiodarone use, and CYP2C9*3 and VKORC1 variants in both races, by CYP2C9*2 and CYP4F2 variants in European Americans, and by rs12777823 in African Americans. CYP2C9*2 was associated with a lower dose only among European Americans (20.6% vs 3.0%, P < .001) and rs12777823 only among African Americans (12.3% vs 2.3%, P = .006). Although VKORC1 was associated with dose decrease in both races, the proportional decrease was higher among European Americans (28.9% vs 19.9%, P = .003) compared with African Americans. Race-stratified analysis improved dose prediction in both race groups compared with race-combined analysis. We demonstrate that the effect of predictors on warfarin dose differs by race, which may explain divergent findings reported by recent warfarin pharmacogenetic trials. We recommend that warfarin dosing algorithms should be stratified by race rather than adjusted for race.

Topics: Algorithms; Anticoagulants; Black or African American; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Genotype; Humans; Male; Middle Aged; Pharmacogenetics; Polymorphism, Genetic; Prognosis; Prospective Studies; Racial Groups; Regression Analysis; Renal Insufficiency, Chronic; Venous Thromboembolism; Vitamin K Epoxide Reductases; Warfarin; White People

Time in therapeutic range (TTR) of international normalized ratio (INR) of 2.0 to 3.0 is important for the safety and effectiveness of warfarin anticoagulation. There are few data on TTR among patients with atrial fibrillation (AF) in community-based clinical practice.. Using the US Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), we examined TTR (using a modified Rosendaal method) among 5,210 patients with AF on warfarin and treated at 155 sites. Patients were grouped into quartiles based on TTR data. Multivariable logistic regression modeling with generalized estimating equations was used to determine patient and provider factors associated with the lowest (worst) TTR.. Overall, 59% of the measured INR values were between 2.0 and 3.0, with an overall mean and median TTR of 65% ± 20% and 68% (interquartile range [IQR] 53%-79%). The median times below and above the therapeutic range were 17% (IQR 8%-29%) and 10% (IQR 3%-19%), respectively. Patients with renal dysfunction, advanced heart failure, frailty, prior valve surgery, and higher risk for bleeding (ATRIA score) or stroke (CHA2DS2-VASc score) had significantly lower TTR (P < .0001 for all). Patients treated at anticoagulation clinics had only slightly higher median TTR (69%) than those not (66%) (P < .0001).. Among patients with AF in US clinical practices, TTR on warfarin is suboptimal, and those at highest predicted risks for stroke and bleeding were least likely to be in therapeutic range.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Frail Elderly; Heart Failure; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; International Normalized Ratio; Logistic Models; Male; Middle Aged; Registries; Renal Insufficiency, Chronic; Risk Factors; Stroke; Time Factors; Treatment Outcome; United States; Warfarin

Renal insufficiency increases the risk of stroke and bleeding in atrial fibrillation patients. Although vitamin K antagonists reduce the risk of stroke in patients with moderate renal dysfunction, this observation is less clear in patients with renal impairment. Moreover, the risk of bleeding with vitamin K antagonists increases as renal function worsens. Maintaining international normalized ratio values within therapeutic targets is more difficult in patients with renal dysfunction, and those agents may cause warfarin-related nephropathy and vascular calcification. Rivaroxaban is the only nonvitamin K oral anticoagulant with a dose specifically tested in patients with moderate renal insufficiency. Rivaroxaban is effective for the prevention of stroke in atrial fibrillation patients with moderate renal dysfunction, with a lower risk of intracranial and fatal bleeding.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Vitamin K; Warfarin

The aim of the study was to investigate the incidence and related factors of upper gastrointestinal bleeding (UGIB) in a Chinese population of peripheral arterial disease (PAD).. A total of 850 Chinese PAD patients were followed up for about 6 years. The incidence of UGIB was recorded and related factors were evaluated. A total of 749 PAD patients with complete data were included in the final statistical analysis during the median follow-up time of 69 months. The incidence of UGIB in this PAD population was 8.4% during the follow-up. Univariate analysis indicated that PAD patients with UGIB were older. A higher percentage of patients with UGIB had hypertension, CKD, history of PUD, and used aspirin or warfarin than those without UGIB. But a lower percentage of patients with UGIB used PPI. The Cox regression analysis suggested that older age (HR: 1.035, 95% CI: 1.007-1.064), comorbidities of CKD (HR: 2.410, 95% CI: 1.455-3.993), history of PUD (HR: 2.127, 95% CI: 1.102-4.100), use of aspirin (HR: 1.517, 95% CI: 1.029-2.235) or warfarin (HR: 1.576, 95% CI: 1.002-2.252) were correlated with the higher incidence of UGIB in PAD patients during follow-up. Nevertheless, PPI use (HR: 0.612, 95% CI: 0.392-0.957) was correlated with the lower incidence of UGIB.. There was a high incidence of UGIB in this Chinese population of PAD. Various factors including older age, comorbidities of CKD, history of PUD, use of aspirin or warfarin were correlated with the higher incidence of UGIB. PPI use was able to reduce the incidence of UGIB.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; China; Comorbidity; Female; Fibrinolytic Agents; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Incidence; Male; Middle Aged; Peptic Ulcer; Peripheral Arterial Disease; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors; Time Factors; Warfarin

Topics: Calciphylaxis; Heparin; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Skin Ulcer; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Myocardial Infarction; Renal Insufficiency, Chronic; Warfarin

Conflicting evidence exists regarding the association between warfarin treatment, death, and ischemic stroke incidence in patients with advanced chronic kidney disease (CKD) and atrial fibrillation.. To study outcomes associated with warfarin treatment in relation to kidney function among patients with established cardiovascular disease and atrial fibrillation.. Observational, prospective, multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry (2003-2010), which includes all Swedish hospitals that provide care for acute cardiac diseases. Participants included consecutive survivors of an acute myocardial infarction (MI) with atrial fibrillation and known serum creatinine (N = 24,317), including 21.8% who were prescribed warfarin at discharge. Chronic kidney disease stages were classified according to estimated glomerular filtration rate (eGFR).. (1) Composite end point analysis of death, readmission due to MI, or ischemic stroke; (2) bleeding (composite of readmission due to hemorrhagic stroke, gastrointestinal bleeding, bleeding causing anemia, and others); or (3) the aggregate of these 2 outcomes within 1 year from discharge date.. A total of 5292 patients (21.8%) were treated with warfarin at discharge, and 51.7% had manifest CKD (eGFR <60 mL/min/1.73 m2 [eGFR<60]). Compared with no warfarin use, warfarin was associated with a lower risk of the first composite outcome (n = 9002 events) in each CKD stratum for event rates per 100 person-years: eGFR>60 event rate, 28.0 for warfarin vs 36.1 for no warfarin; adjusted hazard ratio (HR), 0.73 (95% CI, 0.65 to 0.81); eGFR>30-60: event rate, 48.5 for warfarin vs 63.8 for no warfarin; HR, 0.73 (95% CI, 0.66 to 0.80); eGFR>15-30: event rate, 84.3 for warfarin vs 110.1 for no warfarin; HR, 0.84 (95% CI, 0.70-1.02); eGFR≤15: event rate, 83.2 for warfarin vs 128.3 for no warfarin; HR, 0.57 (95% CI, 0.37-0.86). The risk of bleeding (n = 1202 events) was not significantly higher in patients treated with warfarin in any CKD stratum for event rates per 100 person-years: eGFR>60 event rate, 5.0 for warfarin vs 4.8 for no warfarin; HR, 1.10 (95% CI, 0.86-1.41); eGFR>30-60 event rate, 6.8 for warfarin vs 6.3 for no warfarin; HR, 1.04 (95% CI, 0.81-1.33); eGFR>15-30 event rate, 9.3 for warfarin vs 10.4 for no warfarin; HR, 0.82 (95% CI, 0.48-1.39); eGFR≤15 event rate, 9.1 for warfarin vs 13.5 for no warfarin; HR, 0.52 (95% CI, 0.16-1.65). Warfarin use in each CKD stratum was associated with lower hazards of the aggregate outcome (n = 9592 events) for event rates per 100 person-years: eGFR>60 event rate, 32.1 for warfarin vs 40.0 for no warfarin; HR, 0.76 (95% CI, 0.69-0.84); eGFR>30-60 event rate, 53.6 for warfarin vs 69.0 for no warfarin; HR, 0.75 (95% CI, 0.68-0.82); eGFR>15-30 event rate, 90.2 for warfarin vs 117.7 for no warfarin; HR, 0.82 (95% CI, 0.68-0.99); eGFR≤15 event rate, 86.2 for warfarin vs 138.2 for no warfarin; HR, 0.55 (95% CI, 0.37-0.83).. Warfarin treatment was associated with a lower 1-year risk for the composite outcome of death, MI, and ischemic stroke without a higher risk of bleeding in consecutive acute MI patients with atrial fibrillation. This association was not related to the severity of concurrent CKD.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Patient Readmission; Prospective Studies; Registries; Renal Insufficiency, Chronic; Risk; Stroke; Sweden; Thromboembolism; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Myocardial Infarction; Renal Insufficiency, Chronic; Warfarin

Anticoagulants are used to reduce the risk of stroke in patients with atrial fibrillation (Af) and chronic kidney disease (CKD). Warfarin is one of the commonly used anticoagulants; however, its effect on renal function remains unclear.. In a retrospective cohort study (January 2001 - July 2013), we surveyed data charts from 2,450 patients with stage 3 - 5 CKD, and enrolled 159 patients with Af. In total, 104 patients had a CHADS2 score of >= 2 (congestive heart failure, hypertension, >= 75 years old, diabetes, 1 point; prior stroke or transient ischemic attack or thromboembolism, 2 points). These patients were categorized into groups A and B based on warfarin treatment. Group A included 73 patients and was not undergoing warfarin treatment and group B included 31 patients undergoing warfarin treatment. The baseline demographic and biochemical data as well as changes in estimated glomerular filtration rate (eGFR) after 6, 12, and 18 months of warfarin treatment were analyzed. We also studied censored patient survival over 12 years using Kaplan-Meier model.. The mean international normalization ratio (INR) of warfarin treatment in group B was 1.92 ± 1.04. Moreover, group B showed a significant increase in eGFR. The maximum improvement was at 6 months (mean eGFR increased from 25.97 to 31.12 mL/min; p = 0.01) and lasted for up to 18 months (eGFR 28.65 mL/min). Despite higher initial CHADS2 scores, group B showed a superior survival rate compared with group A (p = 0.02).. Lower doses of warfarin may protect against renal dysfunction and could be beneficial for treatment of stage 3 - 5 CKD with Af.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Disease Progression; Female; Glomerular Filtration Rate; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Kidney; Male; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Stroke; Time Factors; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Myocardial Infarction; Renal Insufficiency, Chronic; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Myocardial Infarction; Renal Insufficiency, Chronic; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Myocardial Infarction; Renal Insufficiency, Chronic; Warfarin

The balance between stroke reduction and increased bleeding associated with antithrombotic therapy among patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is controversial.. This study assessed the risk associated with CKD in individual CHA₂DS₂-VASc (Congestive heart failure; Hypertension; Age ≥75 years; Diabetes mellitus; previous Stroke, transient ischemic attack, or thromboembolism; Vascular disease; Age 65 to 74 years; Sex category) strata and the net clinical benefit of warfarin in patients with AF and CKD in a nationwide cohort.. By individual-level linkage of nationwide Danish registries, we identified all patients discharged with nonvalvular AF from 1997 to 2011. The stroke risk associated with non-end-stage CKD and end-stage CKD (e.g., patients on renal replacement therapy [RRT]) was estimated using Cox regression analyses. The net clinical benefit of warfarin was assessed using 4 endpoints: a composite endpoint of death/hospitalization from stroke/bleeding; a composite endpoint of fatal stroke/fatal bleeding; cardiovascular death; and all-cause death.. From nonvalvular AF patients (n = 154,259), we identified 11,128 patients (7.2%) with non-end-stage CKD and 1,728 (1.1%) receiving RRT. In all CHA₂DS₂-VASc risk groups, RRT was independently associated with a higher risk of stroke/thromboembolism, from a 5.5-fold higher risk in patients with CHA₂DS₂-VASc score = 0 to a 1.6-fold higher risk in patients with CHA₂DS₂-VASc score ≥2. In patients receiving RRT with CHA₂DS₂-VASc score ≥2, warfarin was associated with lower risk of all-cause death (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.72 to 0.99). In non-end-stage CKD patients with CHA₂DS₂-VASc score ≥2, warfarin was associated with a lower risk of a composite outcome of fatal stroke/fatal bleeding (HR: 0.71, 95% CI: 0.57 to 0.88), a lower risk of cardiovascular death (HR: 0.80, 95% CI: 0.74 to 0.88), and a lower risk of all-cause death (HR: 0.64, 95% CI: 0.60 to 0.69).. CKD is associated with a higher risk of stroke/thromboembolism across stroke risk strata in AF patients. High-risk CKD patients (CHA₂DS₂-VASc ≥2) with AF benefit from warfarin treatment for stroke prevention.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cohort Studies; Denmark; Female; Follow-Up Studies; Hemorrhage; Hospitalization; Humans; Male; Proportional Hazards Models; Registries; Renal Insufficiency, Chronic; Renal Replacement Therapy; Risk Assessment; Stroke; Thromboembolism; Warfarin

Vascular calcification has emerged as an independent risk factor for cardiovascular morbidity and mortality, especially in chronic kidney disease. Deficiencies in calcium-regulatory proteins directly relate to development of calcifications. McCabe and colleagues report that vitamin K is a key regulator of vascular calcification, via carboxylation of vitamin K-dependent proteins such as matrix Gla protein. Knowledge about vitamin K status may propel therapeutic strategies to prevent and treat vascular calcification with high vitamin K supplementation.

Topics: Animals; Anticoagulants; Arteries; Dietary Supplements; Male; Renal Insufficiency, Chronic; Vascular Calcification; Vitamin K 1; Warfarin

Warfarin is a well-established cause of gross hematuria. However, impaired kidney function does not occur except in the rare instance of severe blood loss or clot formation that obstructs the urinary tract. It has been recently described an entity called warfarin-related nephropathy, in which acute kidney injury is caused by glomerular hemorrhage and renal tubular obstruction by red blood cell casts. We report a patient under warfarin treatment with chronic kidney disease, macroscopic hematuria and acute kidney injury. A renal biopsy showed massive occlusion of renal tubules by red blood cells and casts. The possible relationship of the warfarin therapy, intratubular hemorrhage and acute kidney injury is discussed.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Hematuria; Humans; Kidney Glomerulus; Male; Renal Insufficiency, Chronic; Warfarin

Thoracentesis is commonly performed to evaluate pleural effusions. Many medications (warfarin, heparin, clopidogrel) or physiological factors (elevated International Normalized Ratio [INR], thrombocytopenia, uremia) increase the risk for bleeding. Frequently these medications are withheld or transfusions are performed to normalize physiological parameters before a procedure. The safety of performing thoracentesis without correction of these bleeding risks has not been prospectively evaluated.. This prospective observational cohort study enrolled 312 patients who underwent thoracentesis. All patients were evaluated for the presence of risk factors for bleeding. Hematocrit levels were obtained pre- and postprocedure, and the occurrence of postprocedural hemothorax was evaluated.. Thoracenteses were performed in 312 patients, 42% of whom had a risk for bleeding. Elevated INR, secondary to liver disease or warfarin, and renal disease were the two most common etiologies for bleeding risk, although many patients had multiple potential bleeding risks. There was no significant difference in pre- and postprocedural hematocrit levels in patients with a bleeding risk when compared with patients with no bleeding risk. No patient developed a hemothorax as a result of the thoracentesis.. This single-center, observational study suggests that thoracentesis may be safely performed without prior correction of coagulopathy, thrombocytopenia, or medication-induced bleeding risk. This may reduce the morbidity associated with transfusions or withholding of medications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Clopidogrel; Cohort Studies; Drainage; Female; Hepatic Insufficiency; Humans; International Normalized Ratio; Male; Middle Aged; Platelet Aggregation Inhibitors; Pleural Effusion; Postoperative Hemorrhage; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Thrombocytopenia; Ticlopidine; Warfarin

The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease, with vascular calcification being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This γ-glutamyl carboxylase substrate is an essential cofactor in the activation of several extracellular matrix proteins that inhibit calcification. Warfarin, a common therapy in dialysis patients, inhibits the recycling of vitamin K and thereby decreases the inhibitory activity of these proteins. In this study, we sought to determine whether modifying vitamin K status, either by increasing dietary vitamin K intake or by antagonism with therapeutic doses of warfarin, could alter the development of vascular calcification in male Sprague-Dawley rats with adenine-induced CKD. Treatment of CKD rats with warfarin markedly increased pulse pressure and pulse wave velocity, as well as significantly increased calcium concentrations in the thoracic aorta (3-fold), abdominal aorta (8-fold), renal artery (4-fold), and carotid artery (20-fold). In contrast, treatment with high dietary vitamin K1 increased vitamin K tissue concentrations (10-300-fold) and blunted the development of vascular calcification. Thus, vitamin K has an important role in modifying mechanisms linked to the susceptibility of arteries to calcify in an experimental model of CKD.

Topics: Adenine; Animals; Anticoagulants; Arteries; Biomarkers; Blood Pressure; Dietary Supplements; Disease Models, Animal; Disease Progression; Male; Osteocalcin; Pulse Wave Analysis; Rats; Rats, Sprague-Dawley; Renal Insufficiency, Chronic; Time Factors; Vascular Calcification; Vitamin K 1; Vitamin K 2; Warfarin

Practice-based research plays a pivotal role for improving patient care as its primary intent is to solve a clinical dilemma or problem encountered in clinical practice. Its results are immediately applicable to day-to-day clinical practice and essential to the growth of an evidence-based clinical practice. This review emphasizes the importance of this type of research. In addition, it serves to identify common sources for project conception and gives examples based on personal experiences of the author as a clinical practitioner, educator, and researcher. Common barriers to practice-based research are discussed as well as potential solutions offered for consideration.

Topics: Brain Injuries; Calcium; Enteral Nutrition; Evidence-Based Medicine; Food-Drug Interactions; Humans; Hypocalcemia; Insulin; Obesity; Pancreatitis; Phosphorus; Renal Insufficiency, Chronic; Research; Treatment Outcome; Warfarin

Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions.. Using Danish national registries, we identified all patients discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. The risk of stroke or systemic thromboembolism and bleeding associated with non-end-stage chronic kidney disease and with end-stage chronic kidney disease (i.e., disease requiring renal-replacement therapy) was estimated with the use of time-dependent Cox regression analyses. In addition, the effects of treatment with warfarin, aspirin, or both in patients with chronic kidney disease were compared with the effects in patients with no renal disease.. Of 132,372 patients included in the analysis, 3587 (2.7%) had non-end-stage chronic kidney disease and 901 (0.7%) required renal-replacement therapy at the time of inclusion. As compared with patients who did not have renal disease, patients with non-end-stage chronic kidney disease had an increased risk of stroke or systemic thromboembolism (hazard ratio, 1.49; 95% confidence interval [CI], 1.38 to 1.59; P<0.001), as did those requiring renal-replacement therapy (hazard ratio, 1.83; 95% CI, 1.57 to 2.14; P<0.001); this risk was significantly decreased for both groups of patients with warfarin but not with aspirin. The risk of bleeding was also increased among patients who had non-end-stage chronic kidney disease or required renal-replacement therapy and was further increased with warfarin, aspirin, or both.. Chronic kidney disease was associated with an increased risk of stroke or systemic thromboembolism and bleeding among patients with atrial fibrillation. Warfarin treatment was associated with a decreased risk of stroke or systemic thromboembolism among patients with chronic kidney disease, whereas warfarin and aspirin were associated with an increased risk of bleeding. (Funded by the Lundbeck Foundation.).

Topics: Aged; Aspirin; Atrial Fibrillation; Female; Hematologic Agents; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Myocardial Infarction; Proportional Hazards Models; Renal Insufficiency, Chronic; Renal Replacement Therapy; Risk; Stroke; Thromboembolism; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Warfarin

Topics: Aspirin; Atrial Fibrillation; Female; Hematologic Agents; Hemorrhage; Humans; Male; Renal Insufficiency, Chronic; Stroke; Warfarin

Topics: Aspirin; Atrial Fibrillation; Female; Hematologic Agents; Hemorrhage; Humans; Male; Renal Insufficiency, Chronic; Stroke; Warfarin

Topics: Aspirin; Atrial Fibrillation; Female; Hematologic Agents; Hemorrhage; Humans; Male; Renal Insufficiency, Chronic; Stroke; Warfarin

There is growing evidence that kidney disease affects hepatically cleared drugs. Accordingly, we hypothesized that chronic kidney disease (CKD) would disrupt anticoagulation of warfarin-treated patients and thereby increase the amount of management required to maintain appropriate anticoagulation. Specifically, we anticipated that more dose manipulations (both dose changes and transient dose adjustments) and shorter times between scheduled clinic visits would be required for anticoagulation patients with CKD.. To determine how CKD affected warfarin maintenance dose, anticoagulation stability, the proportion of clinic visits that necessitated a dose manipulation (either a change in the prescribed weekly dose or a transient dose adjustment), and the length of time between scheduled visits in 2 pharmacist-managed anticoagulation clinics.. Our retrospective, cohort chart review investigated warfarin response in anticoagulation clinic patients. From the clinic database of patients with an international normalized ratio (INR) target range of 2.0-3.0, we matched 20 of 24 patients with CKD (estimated creatinine clearance less than 60 mL per minute) to 20 comparison group patients (estimated creatinine clearance greater than 60 mL per minute) based on parameters demonstrated to affect warfarin dose: ethnicity, gender, age, body surface area, and simvastatin use. We calculated the average weekly dose used to maintain target INR (assessment period range=116-1,408 days). To evaluate anticoagulation stability and patient management, we quantified several parameters, including the percentage of total time in therapeutic range, the proportion of clinic visits that required a dose change, and the time between scheduled visits. We compared group means using t-tests, and categorical data were compared using Fisher's exact test.. Our population was predominantly female (75%) and of African ancestry (95%); average age 60 years. Patients with CKD required a 24% lower dose than the comparison group (mean [SD]=35.9 [10.7] vs. 47.0 [11.2] mg per week, P=0.003) and spent less time in therapeutic range required increased clinic management versus the comparison group, as indicated by a significantly higher proportion of clinic visits at which dose changes occurred (22% vs. 12%, P<0.001) and a decreased time between scheduled visits (mean [SD] of 16.0 [3.2] days vs. 19.7 [3.4] days, respectively, P=0.001).. CKD was associated with both decreased warfarin maintenance dose and decreased anticoagulation stability which, in turn, required more frequent and intensive anticoagulation clinic management.

Topics: Adult; Aged; Ambulatory Care Facilities; Anticoagulants; Cohort Studies; Creatinine; Databases, Factual; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; International Normalized Ratio; Kidney Failure, Chronic; Male; Middle Aged; Pharmacists; Renal Insufficiency, Chronic; Retrospective Studies; Warfarin; Young Adult

We had previously reported that acute kidney injury (AKI) in warfarin-treated chronic kidney disease (CKD) patients may occur shortly after an acute increase in the International Normalization Ratio (INR) >3.0 with formation of occlusive red blood casts. Recovery from this warfarin-associated AKI is poor. Here we investigated whether excessive warfarin therapy could accelerate the progression of CKD.. We analyzed serum creatinine (SC) and INR in 103 consecutive CKD patients on warfarin therapy in our Nephrology program from 2005 to the present.. Forty-nine patients experienced at least 1 episode of INR >3.0. Of these, 18 patients (37%, Group 1) developed an unexplained increase in SC > or =0.3 mg/dl coincident with INR >3.0 (mean SC increase 0.61 +/- 0.44 mg/dl); 31 patients (63%, Group 2) showed stable SC (mean SC change 0.04 +/- 0.19 mg/dl). Subsequent CKD progression was accelerated in Group 1, but not in Group 2. The 2 groups were not different with respect to demographics, comorbidities, blood pressure, or therapies. However, African Americans were overrepresented in Group 1 (p = 0.035).. Overanticoagulation is associated with faster progression of CKD in a high percentage of patients. Our results indicate the need for prospective trials. Nevertheless, we suggest that our findings are sufficiently compelling at this point to justify extra caution in warfarin-treated CKD patients to avoid overanticoagulation.

Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Creatinine; Disease Progression; Female; Humans; International Normalized Ratio; Male; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; Treatment Outcome; Warfarin