warfarin and Renal-Insufficiency

Direct oral anticoagulants (DOACs) are increasingly prescribed instead of warfarin for chronic anticoagulation for ease of dosing, fewer interactions, and less stringent monitoring. However, it is important to consider indications and comorbidities for which warfarin is still the preferred anticoagulant. This review aims to capture these clinical scenarios in which warfarin may still be preferred over DOACs.. We undertook a comprehensive literature search using the PubMed database. Key search terms were based on DOAC clinical trial exclusion criteria, as well as indications and conditions in which the use of DOACs for anticoagulation has suggested harm. Society guidelines and tertiary literature were used to inform expert opinion where necessary. Studies were included if they investigated the use of DOACs or warfarin in the identified indications or conditions.. Currently, evidence for the use of warfarin over DOACs for anticoagulation is strongest for patients with prosthetic valves, antiphospholipid syndrome, or a high risk of gastrointestinal bleeding. For several clinical situations, including mitral stenosis, obesity, altered gastrointestinal anatomy, pulmonary arterial hypertension, renal or hepatic impairment, and left ventricular thrombus, evidence is lacking but may eventually support the use of DOACs. Depending on indication and condition, appropriateness of DOAC use may vary by agent.. New evidence continues to support new indications and conditions in which DOACs may be appropriate to use for anticoagulation. There are key clinical scenarios, however, in which emerging literature continues to support warfarin as the preferred anticoagulant.

Topics: Anticoagulants; Antiphospholipid Syndrome; Atrial Fibrillation; Blood Coagulation; Comorbidity; Drug Interactions; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Humans; Liver Failure; Medication Adherence; Mitral Valve Stenosis; Overweight; Pulmonary Arterial Hypertension; Renal Insufficiency; Stroke; Warfarin

Due to the high risk of ischemic and arterial or venous bleeding events in atrial fibrillation (AF) or venous thromboembolism (VTE) patients with renal impairment (RI), selection of appropriate anticoagulant regimen is important. Therefore, we systematically reviewed and compared the safety and effects of oral anticoagulants in AF and VTE patients with RI.. Eligible articles were identified through a literature search in PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library for studies published between January 2008 and November 2020. Network meta-analysis was conducted with STATA 14.0 to analyze the effects and safety of each drug with regard to different levels of renal function.. 15 studies including 82,931 patients (76,957 with AF and 5974 with VTE) were analyzed. Compared with those of warfarin, the risk ratios of effect and safety outcomes of apixaban were 0.70 (95% confidence interval [CI] 0.60-0.82) and 0.56 (95% CI 0.42-0.76) in AF patients and 0.33 (95% CI 0.19-0.59) and 0.95 (95% CI 0.68-1.34) in VTE patients. Apixaban had the first or second highest probability of being ranked first with respect to surface under the cumulative ranking curve (SUCRA) scores in the prevention of major bleeding events, while in the prevention of ischemic events, rivaroxaban showed a higher SUCRA score (0.78-0.92) in mild RI patients and dabigatran showed a higher SUCRA value (0.90-0.99) in moderate RI patients.. In the systematic review and meta-analysis, for AF or VTE patients with RI, direct oral anticoagulants performed comparably to or better than warfarin with regard to safety and effects. The network meta-analysis indicated that for patients with mild RI, apixaban might be safer for patients with a lower risk of ischemic events, while rivaroxaban might be suitable for patients with a lower risk of bleeding events. For patients with moderate RI, apixaban could reduce the risk of ischemic events without increasing the risk of bleeding events. For AF patients with severe RI, apixaban, rivaroxaban, and warfarin showed a similar effect. These results might provide suggestions for clinical arterial and venous thrombosis prevention.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Network Meta-Analysis; Renal Insufficiency; Rivaroxaban; Venous Thromboembolism; Warfarin

Patients with warfarin have a potential risk of warfarin-related nephropathy, which could result in the discontinuation of anticoagulation therapy. The question of whether non-vitamin K antagonist oral anticoagulants (NOACs) use is associated with increased risk of renal impairment in atrial fibrillation (AF) patients remains unanswered.. Studies were systematically searched through Medline, Embase, Cochrane Library databases, and ClinicalTrials.gov Website. Randomized controlled trials (RCTs) reporting renal impairment events and observational nationwide database studies presenting adjusted hazard ratio (HR) in AF patients with NOACs were identified. The Primacy outcome was renal impairment, defined as a composite of any renal disorder. The secondary outcomes were narrow definition of renal failure (including renal failure, acute renal failure, chronic renal failure, acute prerenal failure and postrenal failure) and individual renal impairment reported in involved studies. HR and 95% confidence intervals (95%CI) were calculated using fixed- or random-effects models according to the extent of heterogeneity. Subgroup analyses were conducted according to individual NOACs, study types and different controls.. Totally, 189,483 patients from 11 RCTs and 3 observational database studies were included in the analysis (119,188 patients with NOACs and 70,295 patients with vitamin K Antagonists or acetylsalicylic acid). Overall results indicated a significantly lower risk of renal impairment in AF patients with NOACs versus VKAs/acetylsalicylic acid (HR: 0.67, 95%CI: 0.62-0.73). Results of narrow definition of renal impairment were accordant with the primacy outcome (HR: 0.65, 95%CI: 0.60-0.71). Compared with VKAs or acetylsalicylic acid, dabigatran (HR: 0.64, 95%CI: 0.56-0.72), rivaroxaban (HR: 0.66, 95%CI: 0.55-0.77) and apixaban (HR: 0.73, 95%CI: 0.59-0.87) were all associated with a significantly lower risk of renal impairment, with the exception of edoxaban (HR: 0.79, 95%CI: 0.30-1.27).. Patients with NOACs might bring about a lower risk of renal impairment compared to VKA or acetylsalicylic acid. Further specialized designs of RCTs and real-world studies on evaluation of renal function are warranted to obtain a robust result on this issue.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Randomized Controlled Trials as Topic; Renal Insufficiency; Warfarin

The present article provides an update on anticoagulant treatment in patients with atrial fibrillation in distinct clinical scenarios requiring particular considerations, such as ischaemic heart disease, electrical cardioversion, pulmonary vein ablation, the presence of valvular disease with or without prosthetic valves, and renal insufficiency, as well as old age and frailty. In patients with non-valvular atrial fibrillation, the presence of renal insufficiency increases both thrombotic and haemorrhagic risk. In mild and moderate stages, direct-acting anticoagulants confer a greater benefit than warfarin, although they usually require dose adjustment. In renal failure/dialysis, there is no solid evidence that warfarin is beneficial and the use of direct-acting anticoagulants is not recommended. Because of its pathophysiology, oral anticoagulation could have a beneficial effect in patients with heart disease. However, vitamin K antagonists have not shown a satisfactory risk-benefit ratio. In contrast, direct-acting anticoagulants, at reduced doses, could have a beneficial effect in this scenario in association with antiplatelet agents. The use of direct-acting anticoagulants prior to electrical cardioversion in patients with non-valvular atrial fibrillation seems to be associated with a risk of cardioembolic events that is at least comparable to that of vitamin K antagonists. Their use avoids delay in the application of electrical cardioversion in patients without adequate INR levels. In the context of their use before and after atrial fibrillation ablation, dabiga-tran and rivaroxaban have demonstrated at least non-inferiority with vitamin K antagonists in terms of safety. In patients with any type or grade of valvular disease and atrial fibrillation, the indication of antithrombo-tic treatment must be evaluated in the same way as in patients with atrial fibrillation and no valvular di-sease. Whenever anticoagulation is required, direct-acting anticoagulants are the treatment of choice in nearly all situations, except in patients with mechanical valves or who have significant rheumatic mitral disease, who should be treated with vitamin K antagonists. The choice of appropriate antithrombotic stra-tegy in frail elderly patients is complex and involves multiple factors beyond assessment of embolic and haemorrhagic risk. Comprehensive geriatric assessment is essential for an individualised final decision. Moreover, any such decision should be consensus-based

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Electric Countershock; Fibrinolytic Agents; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Meta-Analysis as Topic; Multicenter Studies as Topic; Myocardial Ischemia; Renal Insufficiency; Risk Assessment; Secondary Prevention; Thromboembolism; Thrombophilia; Vitamin K; Warfarin

Renal impairment increases risk of stroke and systemic embolic events and bleeding in patients with atrial fibrillation. Direct oral anticoagulants (DOACs) have varied dependence on renal elimination, magnifying the importance of appropriate patient selection, dosing, and periodic kidney function monitoring. In randomized controlled trials of nonvalvular atrial fibrillation, DOACs were at least as effective and associated with less bleeding compared with warfarin. Each direct oral anticoagulant was associated with reduced risk of stroke and systemic embolic events and major bleeding compared with warfarin in nonvalvular atrial fibrillation patients with mild or moderate renal impairment. Renal function decrease appears less impacted by DOACs, which are associated with a better risk-benefit profile than warfarin in patients with decreasing renal function over time. Limited data address the risk-benefit profile of DOACs in patients with severe impairment or on dialysis.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Pharmaceutical Research; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency; Risk Assessment; Rivaroxaban; Stroke; Therapeutic Equivalency; Thiazoles; Warfarin

Venous thromboembolism (VTE) is one of the leading causes of death in cancer patients, which are known to have a 5- to 7-fold increased risk for VTE. The anticoagulant treatment of VTE in cancer patients is less effective with a three-fold increased risk of VTE recurrence compared to non-cancer patients, and it is less safe with more than double rates of major bleeding. Compared to vitamin-K antagonists (VKA), long-term secondary prevention with low molecular weight heparin (LMWH) has been shown to reduce the risk of recurrent VTE in cancer-associated thrombosis (CAT), and therefore, current international guidelines recommend the use of LMWH over VKA. With increasing age, cancer prevalence and VTE incidence increase while renal function decreases. Anti-cancer treatment may impair renal function additionally. Therefore, renal insufficiency is a frequent challenge in CAT patients, which is associated with a higher risk of both bleeding and recurrent VTE. Both VKA and LMWH may be associated with less efficacy and higher bleeding risk in renal insufficiency. Unfortunately, there is a lack of prospective data on renal insufficiency and CAT. A recent sub-analysis from a large randomized controlled trial shows that the bleeding risk in patients with severe renal insufficiency in CAT is not elevated with the use of LMWH compared to VKA while efficacy is maintained. In addition, LMWH treatment has several practical advantages over VKA, particularly in patients with CAT while they are receiving anti-cancer treatment.

Topics: Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Recurrence; Renal Insufficiency; Venous Thromboembolism; Vitamin K; Warfarin

To investigate the relative effect of warfarin versus non-vitamin K oral anticoagulants (NOACs) in thrombotic and bleeding outcomes in subgroups of atrial fibrillation (AF) patients with varying degrees of renal dysfunction.. Systemic review and meta-regression analyses on NOACs versus warfarin, supplemented with indirect comparisons were conducted. The eligibility criteria for inclusion were randomised controlled trials comparing NOACs against warfarin for stroke prevention in AF patients. Outcomes of interest were stroke or systemic embolism (SE) and major bleeding.. Five studies comprising 72,845 AF patients randomised to either a NOAC or warfarin were included in the meta-regression analysis. A shift in strata from no renal impairment to renal impairment resulted in a non-significant impact on bleeding and stroke/SE, indicating similar safety and efficacy, despite renal function status. Apixaban was associated with less major bleeding compared to dabigatran and rivaroxaban but not edoxaban in patients with moderate renal impairment. For efficacy outcomes, only dabigatran 150 mg was statistically significantly favoured compared to edoxaban 30 mg. For efficacy outcomes in mild renal impairment, both dabigatran 150 mg and rivaroxaban 10 mg (J-ROCKET) were statistically significantly favoured against edoxaban 30 mg.. Non-vitamin K oral anticoagulants had similar efficacy and safety compared to warfarin across different levels of renal function. Indirect comparisons suggest that apixaban and edoxaban were associated with a better safety profile in patients with moderate renal impairment. However, caution is warranted when interpreting indirect comparisons of drugs investigated in different trials. Prescribers should fit the most appropriate NOAC to the AF patient characteristics (and vice versa) to individualise effective stroke prevention.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency; Stroke; Treatment Outcome; Vitamin K; Warfarin

The use of new oral anticoagulants (NOACs) in patients with impaired renal function has raised major concerns, in particular the possibility of an increased risk of bleeding due to accumulation. The aims of this work were to assess the safety of NOACs in patients with renal failure and describe the relationship between clinical events and drug renal excretion magnitude.. All phase III trials comparing NOACs with vitamin K antagonists (VKAs) in patients with estimated glomerular filtration (eGFR) rate < 50 mL min(-1) were eligible. The main safety and efficacy outcomes were major bleeding and thrombosis. A meta-regression was performed to estimate the correlation between the treatment effect estimate and the percentage of renal excretion.. Nine studies (12 272 patients) were included. A significantly greater relative reduction in major bleeding was seen for NOACs with renal excretion <50% (RR, 0.61; CI, 0.51-0.74) than for those with high renal excretion (RR, 0.96; CI, 0.85-1.07) (interaction test, P < 0.0001). A linear relationship between the relative risk of major bleeding and the magnitude of renal excretion was found by meta-regression (R(2)  = 0.66, P = 0.03). For thrombosis, a greater treatment effect of NOA vs. INR-adjusted VKA was observed in patients with eGFR < 50 mL min(-1) (RR 0.78, CI 0.67-0.92), but no correlation between treatment effect and renal excretion was found.. New oral anticoagulants were at least as effective as VKAs, with reduced risks of major bleeding and thrombosis in patients with eGFR < 50 mL min(-1) . The renal excretion of these new drugs seemed to modify the safety profile, contrary to the efficacy.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Glomerular Filtration Rate; Hemorrhage; Humans; Renal Insufficiency; Thrombosis; Treatment Outcome; Venous Thromboembolism; Vitamin K; Warfarin

The majority of patients with nonvalvular atrial fibrillation (AF) will require anticoagulation therapy for reducing the risk of stroke, the most devastating complication of AF. Although traditionally vitamin K antagonists have been used for this purpose, they have important limitations that interfere with their use in clinical practice. Different clinical trials have shown the benefits of new oral anticoagulants over warfarin, but patients included in the ROCKET-AF trial were found to be at a higher risk of AF-related complications. Moreover, rivaroxaban has been proven to be effective and safe in patients with AF and moderate renal dysfunction as well as in those with ischemic heart disease. Rivaroxaban is taken only once daily; this may improve medication adherence and, secondarily, it provides a higher protection and reduction in the risk of stroke. This article provides an extensive review of the available evidence about rivaroxaban, with a special focus on nonvalvular AF.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Humans; Ischemic Attack, Transient; Medication Adherence; Morpholines; Renal Insufficiency; Rivaroxaban; Severity of Illness Index; Stroke; Thiophenes; Thromboembolism; Vitamin K; Warfarin

Three new oral anticoagulants have been evaluated in large registration trials and are now available in many jurisdictions for patients with atrial fibrillation. Questions arise whether these drugs are equally effective and safe for all patients. Now when we are moving away from decades with only one orally available drug for anticoagulation there is opportunity to tailor the therapy according to patient characteristics and preferences. This review addresses the interaction of various patient characteristics with the treatment and what features can assist the physician in the choice of anticoagulant for the individual patient.

Topics: Administration, Oral; Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Coumarins; Dabigatran; Female; Hematology; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Renal Insufficiency; Sex Factors; Warfarin

Warfarin significantly reduces thromboembolic risk, but perceptions of associated bleeding risk limit its use. The evidence supporting the association between bleeding and individual patient risks factors is unclear. This systematic review aims to determine the strength of evidence supporting an accentuated bleeding risk when patients with risk factors listed in the warfarin prescribing information are prescribed the drug. A systematic literature search of MEDLINE and Cochrane CENTRAL was conducted to identify studies reporting multivariate relationships between prespecified covariates and the risk of bleeding in patients receiving warfarin. The prespecified covariates were identified based on patient characteristics for bleeding listed in the warfarin package insert. Each covariate was evaluated for its association with specific types of bleeding. The quality of individual evaluations was rated as 'good', 'fair' or 'poor' using methods consistent with those recommended by the Agency for Healthcare Research and Quality (AHRQ). Overall strength of evidence was determined using the Grading of Recommendations Assessment, Development (GRADE) criteria and categorised as 'insufficient', 'very low', 'low', 'moderate' or 'high'. Thirty-four studies, reporting 134 multivariate evaluations of the association between a covariate and bleeding risk were identified. The majority of evaluations had a low strength of evidence for the association between covariates and bleeding and none had a high strength of evidence. Malignancy and renal insufficiency were the only two covariates that had a moderate strength of evidence for their association with major and minor bleeding respectively. The associations between covariates listed in the warfarin prescribing information and increased bleeding risk are not well supported by the medical literature.

Topics: Alcohol Drinking; Anemia; Anticoagulants; Drug Labeling; Heart Diseases; Hemorrhage; Humans; Liver Diseases; Medication Adherence; Mental Disorders; Neoplasms; Prescription Drugs; Renal Insufficiency; Risk Factors; Warfarin

Topics: Animals; Anticoagulants; Calcinosis; Chronic Disease; Humans; Renal Dialysis; Renal Insufficiency; Vascular Diseases; Vitamin K; Vitamin K Deficiency; Warfarin

The management of patients who require temporary interruption of oral anticoagulant therapy because of surgery or other invasive procedures is a clinically important topic because of the increasing prevalence of patients who are receiving oral anticoagulants and the availability of low-molecular-weight heparins (LMWHs), which allow out-of-hospital perioperative anticoagulation. The optimal management of such patients has been hampered by the lack of well-designed prospective studies investigating the efficacy and safety of different perioperative management strategies. The two main issues that need to be considered in perioperative anticoagulant management is the patient's risk of thromboembolic event when anticoagulant therapy is interrupted and the risk of bleeding that is associated with the surgery or procedure. An assessment of these factors will determine the perioperative management approach. The objectives of this review are to focus on practical issues relating to perioperative anticoagulation and the implementation of a perioperative anticoagulation management approach that can be used in everyday clinical practice.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Loss, Surgical; Female; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Middle Aged; Perioperative Care; Postoperative Hemorrhage; Renal Insufficiency; Risk Factors; Thromboembolism; Thrombosis; Venous Thrombosis; Warfarin

This study aimed to analyze the influence of renal insufficiency on the anticoagulant effects and safety of warfarin in Chinese patients. Data on the creatinine levels of participants enrolled in a randomized controlled study were screened and divided into the non-renal insufficiency group, mild renal insufficiency group, and moderate renal insufficiency group, according to the creatinine clearance rate. The primary outcome measures were stable dose and average daily dose of warfarin. Secondary outcome measures were percentage of time in the therapeutic international normalized ratio (INR) (%TTR), and the first time to reach the therapeutic INR. Adverse events included bleeding events, thromboembolic events, and mortality. All participants with renal function test results and a baseline INR of less than 1.5 were included in the primary and secondary outcome analysis. The SPSS Statistics 21.0 software was used for statistical analysis. The randomized controlled trial was registered in Clinicaltrials.gov (NCT02211326). A total of 571 patients were included in this analysis. Multiple regression analysis showed that the renal function was correlated with stable dose, average daily dose, and the first time to reach therapeutic INR after adjusting for confounding factors. However, no correlation was noted between kidney function and %TTR. No significant differences were observed across the various safety parameters among the three groups. Renal function is an important consideration in patients using warfarin.

Topics: Aged; Anticoagulants; Asian People; Creatinine; Dose-Response Relationship, Drug; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Renal Insufficiency; Single-Blind Method; Time Factors; Warfarin

In the Japanese Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (J-ROCKET AF) study, rivaroxaban 15 mg once daily was given to patients with creatinine clearance (CrCl) ≥ 50 ml/min (preserved renal function), and was reduced to 10mg once daily in patients with CrCl 30-49 ml/min (moderate renal impairment). The aim of this subanalysis was to assess the safety and efficacy of the adjusted dose of rivaroxaban compared with warfarin in a cohort with moderate renal impairment.. Compared with patients with preserved renal function, those with moderate renal impairment (22.2% of all randomized patients) had higher rates of bleeding and stroke events irrespective of study treatment. Among those with moderate renal impairment, the principal safety endpoint occurred at 27.76%/year with rivaroxaban vs. 22.85%/year with warfarin (hazard ratio [HR], 1.22; 95% confidence interval [CI]: 0.78-1.91) and the rate of the primary efficacy endpoint was 2.77%/year vs. 3.34%/year (HR, 0.82; 95% CI: 0.25-2.69), respectively. There were no significant interactions between renal function and study treatment in the principal safety and the primary efficacy endpoints (P=0.628, 0.279 for both interactions, respectively).. The safety and efficacy of rivaroxaban vs. warfarin were consistent in patients with moderate renal impairment and preserved renal function.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Asian People; Atrial Fibrillation; Creatinine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Japan; Kidney; Male; Middle Aged; Morpholines; Renal Insufficiency; Reproducibility of Results; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Warfarin

Patients with non-valvular atrial fibrillation (AF) and renal insufficiency are at increased risk for ischaemic stroke and bleeding during anticoagulation. Rivaroxaban, an oral, direct factor Xa inhibitor metabolized predominantly by the liver, preserves the benefit of warfarin for stroke prevention while causing fewer intracranial and fatal haemorrhages.. We randomized 14 264 patients with AF in a double-blind trial to rivaroxaban 20 mg/day [15 mg/day if creatinine clearance (CrCl) 30-49 mL/min] or dose-adjusted warfarin (target international normalized ratio 2.0-3.0). Compared with patients with CrCl >50 mL/min (mean age 73 years), the 2950 (20.7%) patients with CrCl 30-49 mL/min were older (79 years) and had higher event rates irrespective of study treatment. Among those with CrCl 30-49 mL/min, the primary endpoint of stroke or systemic embolism occurred in 2.32 per 100 patient-years with rivaroxaban 15 mg/day vs. 2.77 per 100 patient-years with warfarin [hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.57-1.23] in the per-protocol population. Intention-to-treat analysis yielded similar results (HR 0.86; 95% CI 0.63-1.17) to the per-protocol results. Rates of the principal safety endpoint (major and clinically relevant non-major bleeding: 17.82 vs. 18.28 per 100 patient-years; P = 0.76) and intracranial bleeding (0.71 vs. 0.88 per 100 patient-years; P = 0.54) were similar with rivaroxaban or warfarin. Fatal bleeding (0.28 vs. 0.74% per 100 patient-years; P = 0.047) occurred less often with rivaroxaban.. Patients with AF and moderate renal insufficiency have higher rates of stroke and bleeding than those with normal renal function. There was no evidence of heterogeneity in treatment effect across dosing groups. Dose adjustment in ROCKET-AF yielded results consistent with the overall trial in comparison with dose-adjusted warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Embolism; Female; Hemorrhage; Humans; Male; Morpholines; Renal Insufficiency; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Warfarin

In the present study we aimed to demonstrate the efficacy of short-term pretreatment with finasteride in patients undergoing transurethral resection of the prostate (TUR-P). For this purpose 40 patients with BPH, who were candidates for TUR-P, were randomized into two groups. The first group (n=20) received 5 mg finasteride/day for 4 weeks prior to surgery and the second group (n=20) remained as the control. Patients who underwent prior prostate or urethral surgery and had a diagnosis of prostate cancer or chronic renal failure, patients who received finasteride, aspirin, coumadin or similar anticoagulant drugs prior to surgery and patients who had capsule perforations or open sinuses during the surgery were excluded from the study. All patients had a normal digital rectal examination and PSA values less than 4 ng/ml. As we look at the results there was no statistically significant difference between the finasteride group and control group regarding age, IPSS, PSA, prostate volumes, preoperative serum hemoglobin, hematocrit values and mean operating times and used irrigating fluids. The total amount of bleeding and bleeding per gram resected tissue were significantly lower in the finasteride group regardless of prostate volume. Furthermore the decrease in the hemoglobin and hematocrit values was higher in the control group. As a conclusion four weeks of finasteride pretreatment provided a significant decrease in peroperative bleeding regardless of prostate volume without any major side effects.

Topics: Age Factors; Aged; Anticoagulants; Aspirin; Finasteride; Hemoglobins; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Renal Insufficiency; Risk; Time Factors; Transurethral Resection of Prostate; Urethra; Warfarin

To investigate the relationship of hypercoagulation and renal dysfunction in patients with diabetic nephropathy(DN).. Forty six diabetes type II patients with nephrotic syndrome were divided into 3 groups according to 24 hr creatinine clearance (Ccr) as high, middle and low groups. Fourteen of the 46 patients received warfarin therapy. The parameters of coagulation and fibrolysis as well as renal function were examined.. Patients with moderate and major renal dysfunction (M group and L group) displayed higher activities of coagulation than those with mild renal dysfunction (H group) did. Warfarin could obviously improve the status of coagulation and fibrolysis in patients with DN and delay the progress of renal dysfunction.. Hypercoa-gulation was one of the causes of renal dysfunction in patients with DN.

Topics: Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Male; Metabolic Clearance Rate; Renal Insufficiency; Thrombophilia; Warfarin

In randomized clinical trials (RCTs) of nonvitamin K antagonist oral anticoagulants (NOACs) for acute venous thromboembolism (VTE), ~ 12-13% of patients were elderly and ~ 26% had mild-to-moderate renal impairment. Observational studies are not restricted by the selection and treatment criteria of RCTs. In this ancillary analysis of the RE-COVERY DVT/PE global observational study, we aimed to describe patient characteristics, comorbidities, and anticoagulant therapy for subgroups of age (< or ≥ 75 years) and renal impairment (creatinine clearance [CrCl; estimated with Cockcroft-Gault formula] < 30 [severe], 30 to < 50 [moderate], 50 to < 80 [mild], ≥ 80 [normal] mL/min). Of 6095 eligible patients, 25.3% were aged ≥ 75 years; 38.2% (1605/4203 with CrCl values) had mild-to-moderate renal impairment. Comorbidities were more common in older patients (73.9% aged ≥ 75 vs. 58.1% < 75 years) and in those with mild or moderate versus no renal impairment (75.9%, 80.9%, and 59.3%, respectively). At hospital discharge or 14 days after diagnosis (whichever was later), most patients (53.7% and 55.1%, respectively) in both age groups received NOACs; 20.8% and 23.4%, respectively, received vitamin K antagonists, 19.0% and 21.8% parenteral therapy, 2.3% and 3.8% other anticoagulant treatments. Use of NOACs decreased with worsening renal impairment (none 58.5%, moderate 49.6%, severe 25.7%) and, in younger versus older patients with moderate renal impairment (33.1% vs. 56.1%). In routine practice, there are more elderly and renally impaired patients with VTE than represented in RCTs. Decreasing renal function, but not older age, was associated with less NOAC use. Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT02596230. Decreasing renal function, particularly in the subgroup with CrCl < 30 mL/min, but not older age, was associated with less use of nonvitamin K antagonist oral anticoagulants (NOACs). Nevertheless, more than half of the older patients with moderate renal impairment received a NOAC as their oral anticoagulant.

Topics: Age Factors; Aged; Anticoagulants; Antithrombins; Blood Coagulation; Comorbidity; Dabigatran; Female; Global Health; Humans; Kidney Function Tests; Male; Practice Patterns, Physicians'; Renal Insufficiency; Risk Adjustment; Severity of Illness Index; Venous Thromboembolism; Warfarin

Real-world information regarding the use of direct oral anticoagulants therapy and the outcome in patients with renal dysfunction is limited.. To evaluate the clinical characteristics and outcomes of patients with atrial fibrillation (AF) and severe renal dysfunction who are treated with apixaban.. A sub-analysis was conducted within a multicenter prospective cohort study. The study included consecutive eligible apixaban- or warfarin-treated patients with non-valvular AF and renal impairment (estimated glomerular filtration rate [eGFR] modification of diet in renal disease [MDRD] < 60 ml/min/BSA) were registered. All patients were prospectively followed for clinical events and over a mean period of 1 year. Our sub-analysis included the patients with 15 < eGFR MDRD < 30 ml/min/BSA. The primary outcomes at 1 year were recorded. They included mortality, stroke or systemic embolism, major bleeding, and myocardial infarction as well as their composite occurrence.. The sub-analysis included 155 warfarin-treated patients and 97 apixaban-treated ones. All had 15 < eGFR MDRD < 30 ml/min/BSA. When comparing outcomes for propensity matched groups (n=76 per group) of patients treated by reduced dose apixaban or warfarin, the rates of the 1-year composite endpoint as well as mortality alone were higher among the warfarin group (30 [39.5%] vs. 14 [18.4%], P = 0.007 and 28 [36.8%] vs.12 [15.8%], P = 0.006), respectively. There was no significant difference in the rates of stroke, systemic embolism, or major bleeding.. Apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment.

Topics: Aged; Atrial Fibrillation; Cohort Studies; Dose-Response Relationship, Drug; Drug Monitoring; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Israel; Kidney Function Tests; Male; Myocardial Infarction; Outcome Assessment, Health Care; Pyrazoles; Pyridones; Renal Insufficiency; Stroke; Survival Analysis; Warfarin

To investigate risk factors for severe bleeding during warfarin treatment, including the influence of sex, age, comorbidity and co-medication on bleeding risk.. Patients initiating warfarin treatment between 2007 and 2011 were identified in the nationwide Swedish Prescribed Drug Register, and diagnoses of severe bleeding were retrieved from the National Patient Register. Hazard ratios (HR) with 95% confidence intervals (CI) for severe bleeding were estimated using multiple Cox regression adjusting for indications and including covariates age, sex, comorbidities and co-medications. Interactions between sex and other covariates were investigated.. The study cohort included 232,624 patients ≥ 18 years (101,011 women and 131,613 men). The incidence rate of severe bleeding was 37 per 1000 person-years, lower among women than men with an adjusted HR (95% CI) of 0.84 (0.80-0.88). Incidence of bleeding increased with age, HR 2.88 (2.37-3.50) comparing age ≥ 80 to < 40 years, and comorbidities associated with the highest risk of severe bleeding were prior bleeding, HR 1.85 (1.74-1.97); renal failure, HR 1.82 (1.66-2.00); and alcohol dependency diagnosis, HR 1.79 (1.57-2.05). Other comorbidities significantly associated with bleeding events were hypertension, diabetes, peripheral vascular disease, congestive heart failure, liver failure, stroke/TIA, COPD and cancer.. Most of the well-established risk factors were found to be significantly associated with bleeding events in our study. We additionally found that women had a lower incidence of bleeding. Potential biases are selection effects, residual confounding and unmeasured frailty.

Topics: Adult; Aged; Aged, 80 and over; Alcoholism; Anticoagulants; Atrial Fibrillation; Comorbidity; Female; Hemorrhage; Humans; Male; Middle Aged; Renal Insufficiency; Risk Factors; Warfarin

 Many patients on warfarin therapy often present with supratherapeutic international normalized ratio (INR) levels, resulting from the influence of several patient-specific factors, which have been associated with adverse outcomes..  This article aims to identify risk factors for over-anticoagulation (INR levels ≥4) in a cohort of patients taking warfarin..  A cohort of warfarin users aged 18 to 85 years from January 2005 to April 2013 was identified in The Health Improvement Network U.K. primary care database (.  Among the factors examined, the strongest predictors of over-anticoagulation were warfarin indication (in particular, valvular atrial fibrillation and valve replacement), renal failure (with the risk increasing steeply with decreasing estimated glomerular filtration rate), cancer, anaemia, respiratory infections treated with antibiotics, chronic obstructive pulmonary disease treated with β2-agonists, polypharmacy (≥10 medications), low socio-economic status and residency in rural areas. Similar results were obtained when supratherapeutic levels were defined as INR ≥5 or, alternatively, as INR > 3..  Predictors of supratherapeutic INR levels found in this study might help physicians identify patients where closer INR monitoring is warranted.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Anticoagulants; Blood Coagulation; Case-Control Studies; Databases, Factual; Female; Glomerular Filtration Rate; Humans; International Normalized Ratio; Male; Medical Overuse; Middle Aged; Neoplasms; Odds Ratio; Poverty; Primary Health Care; Pulmonary Disease, Chronic Obstructive; Regression Analysis; Renal Insufficiency; Respiratory Tract Infections; Rural Population; United Kingdom; Warfarin; Young Adult

Atrial fibrillation (AF) increases risk of ischemic stroke, and oral anticoagulation (OAC) increases risk of intracerebral hemorrhage (ICH). This study aimed to compare OAC-treated AF patients with an ischemic stroke/transient ischemic attack (TIA) or spontaneous ICH as their first lifetime cerebrovascular event, especially focusing on patients with therapeutic international normalized ratio (INR).. We assumed that in AF patients suffering ischemic stroke/TIA or ICH, patient characteristics could be different in patients with therapeutic INR than in patients with warfarin.. FibStroke is a multicenter, retrospective registry collating details of AF patients with ischemic stroke/TIA or intracranial hemorrhage in 2003-2012. This substudy included AF patients on OAC with first lifetime ischemic stroke/TIA or spontaneous ICH.. A total of 1457 patients with 1290 ischemic strokes/TIAs and 167 ICHs were identified. Of these, 553 (42.9%) strokes/TIAs and 96 (57.5%) ICHs occurred in patients with INR within therapeutic range. During OAC with therapeutic INR, congestive heart failure (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.18-4.58) and hypercholesterolemia (OR: 2.52, 95% CI: 1.51-4.19) were more common in patients with ischemic stroke/TIA, whereas a history of bleeding (OR: 0.30, 95% CI: 0.11-0.82) was less common when compared with patients with ICH. In the whole cohort, renal impairment (OR: 1.86, 95% CI: 1.23-2.80) and mechanical valve prosthesis (OR: 4.41, 95% CI: 1.32-14.7) were overrepresented in patients with stroke/TIA, whereas aspirin use (OR: 0.52, 95% CI: 0.30-0.91) and high INR (OR: 0.40, 95% CI: 0.33-0.48) were overrepresented in patients with ICH.. In anticoagulated AF patients with therapeutic INR and first lifetime cerebrovascular event, congestive heart failure and hypercholesterolemia were associated with ischemic stroke/TIA and history of bleeding with ICH.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Brain Ischemia; Cerebral Hemorrhage; Chi-Square Distribution; Comorbidity; Drug Monitoring; Female; Finland; Heart Failure; Humans; Hypercholesterolemia; International Normalized Ratio; Ischemic Attack, Transient; Logistic Models; Male; Multivariate Analysis; Odds Ratio; Registries; Renal Insufficiency; Retrospective Studies; Risk Factors; Stroke; Treatment Outcome; Warfarin

The U.S. Food and Drug Administration approval of the use of apixaban in patients with a creatinine clearance (CrCl) of < 15 ml/minute or in those receiving dialysis is based only on pharmacokinetic data as clinical trials of apixaban excluded patients with a CrCl of < 25 ml/minute or a serum creatinine concentration (SCr) of > 2.5 mg/dl. Thus, the objective of this study was to evaluate the safety and effectiveness of apixaban versus warfarin in patients with severe renal impairment.. Retrospective, matched-cohort study.. Community hospital.. A total of 146 adults who received at least one dose of apixaban (73 patients) or warfarin (73 patients) while hospitalized between January 30, 2014, and December 31, 2015, and had a CrCl of < 25 ml/minute or SCr of > 2.5 mg/dl, or who received peritoneal dialysis or hemodialysis, were included. Patients who were taking warfarin and had a therapeutic international normalized ratio on admission were matched consecutively in a 1:1 fashion in chronologic order to patients taking apixaban based on renal function and indication for anticoagulation.. The primary outcome was major bleeding. Secondary outcomes included the composite of bleeding (major bleeding, clinically relevant nonmajor bleeding, and minor bleeding) in addition to documented ischemic stroke or recurrent venous thromboembolism. A nonsignificant difference in the occurrence of major bleeding and composite bleeding was observed between patients who received apixaban compared with those who received warfarin (9.6% vs 17.8%, p=0.149, and 21.9% vs 27.4%, p=0.442, respectively). The occurrence of stroke was similar between the groups (7.5% in each group), and no recurrent venous thromboembolism events were noted in either group during the study period.. Apixaban appears to be a reasonable alternative to warfarin in patients with severe renal impairment.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Hemorrhage; Hospitals, Community; Humans; Male; Peritoneal Dialysis; Pyrazoles; Pyridones; Renal Dialysis; Renal Insufficiency; Retrospective Studies; Stroke; Treatment Outcome; Venous Thromboembolism; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Humans; Registries; Renal Insufficiency; Warfarin

The balance between the efficacy and safety of anticoagulant therapy in patients aged ≥100years receiving anticoagulant therapy for venous thromboembolism (VTE) is uncertain.. We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the rate of VTE recurrences, bleeding events, and mortality appearing during the course of anticoagulant therapy in VTE patients aged ≥100years.. Of 61,173 patients enrolled in RIETE as of January 2016, 47 (0.08%) were aged ≥100years. Of these, 10 (21%) were men, 21 (45%) presented with pulmonary embolism (PE), and 26 with deep vein thrombosis alone. Overall, 35 patients (74%) had severe renal insufficiency, 14 (30%) chronic heart failure, 30 (64%) anemia, 16 (34%) were taking antiplatelets, and 6 (13%) corticosteroids or non-steroidal anti-inflammatory drugs. Most patients (95%) were treated initially with low-molecular-weight heparin (LMWH) (mean daily dose, 168±42IU/kg). Then, 14 (30%) switched to vitamin K antagonists and 29 (62%) kept receiving long-term LMWH therapy (mean, 148±51IU/kg/day). During the course of anticoagulant therapy (mean duration, 139days), mortality was high (15/47; 32%). Two patients died of PE (initial PE one, recurrent PE one) and 5 (11%) had minor bleeding, but no major bleeding was reported.. Among patients with acute VTE aged ≥100years, the risk of VTE recurrences during the course of anticoagulation outweighed the risk of bleeding. Our data suggest the use of standard anticoagulant therapy in this patient population, even if they have severe renal insufficiency.

Topics: Aged, 80 and over; Anemia; Anticoagulants; Comorbidity; Female; Heart Failure; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Pulmonary Embolism; Recurrence; Registries; Renal Insufficiency; Spain; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

Adherence to American College of Chest Physicians (CHEST) guidelines for treatment of acute venous thromboembolism (VTE) has not been formally assessed in the United States, specifically in the subset of patients with renal impairment.. Evaluate adherence to CHEST VTE treatment guidelines.. This retrospective cohort study evaluated patients with acute VTE between January 1, 2010, and December 31, 2011, for the primary outcome of adherence to CHEST VTE treatment guidelines defined as (1) patients receiving an appropriate parenteral anticoagulant and dose based on renal function and weight, (2) at least 5 days of parenteral anticoagulation during warfarin initiation, and (3) an international normalized ratio (INR) value ≥2 documented before discontinuing parenteral agents. Secondary outcomes included recurrent thromboembolism and major bleeding across renal function categories.. Of the 1683 patients included in the final analysis, 1483 (88%) had complete data for all 3 elements of the primary outcome (dose, overlap duration, and INR ≥2.0). VTE guideline adherence was identified in 95% (1408/1483) of these patients. There were 20 major bleeds overall, which occurred in 1.1%, 1.1%, and 1.3% in patients with CrCl <30 mL/min, 30 to 59 mL/min, and ≥60 mL/min, respectively (P = 0.929). Also, 7 recurrent VTE events occurred-3 in patients with CrCl values of 30 to 59 mL/min (0.5%) and 4 in patients with CrCl ≥60 mL/min (0.4%; P = 0.797 across groups).. Adherence to CHEST guidelines was high and resulted in low rates of bleeding and recurrent VTE complications across renal function categories. Further studies of patients with CrCl <30 mL/min are needed.

Topics: Acute Disease; Aged; Anticoagulants; Female; Guideline Adherence; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Practice Guidelines as Topic; Recurrence; Renal Insufficiency; Retrospective Studies; United States; Venous Thromboembolism; Warfarin

Recent evidence has shown that high level of factor VIII is associated with increased risk of thromboembolism. High factor VIII levels are associated with a seven-fold increase in the risk of venous thrombosis. Renal vein thrombosis is usually associated with nephrotic syndrome, procoagulant state or oral contraceptive pills. We report a case of a lady who presented with bilateral renal vein thrombosis due to high factor VIII levels and oral contraceptive pills (OCP) use.

Topics: Adult; Anticoagulants; Contraceptives, Oral; Factor VIII; Female; Heparin; Humans; Renal Insufficiency; Renal Veins; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin

The degree of oxidized cysteine (Cys) 34 in human serum albumin (HSA), as determined by high performance liquid chromatography (HPLC), is correlated with oxidative stress related pathological conditions. In order to further characterize the oxidation of Cys34-HSA at the molecular level and to develop a suitable analytical method for a rapid and sensitive clinical laboratory analysis, the use of electrospray ionization time-of-flight mass spectrometer (ESI-TOFMS) was evaluated. A marked increase in the cysteinylation of Cys34 occurs in chronic liver and kidney diseases and diabetes mellitus. A significant positive correlation was observed between the Cys-Cys34-HSA fraction of plasma samples obtained from 229 patients, as determined by ESI-TOFMS, and the degree of oxidized Cys34-HSA determined by HPLC. The Cys-Cys34-HSA fraction was significantly increased with the progression of liver cirrhosis, and was reduced by branched chain amino acids (BCAA) treatment. The changes in the Cys-Cys34-HSA fraction were significantly correlated with the alternations of the plasma levels of advanced oxidized protein products, an oxidative stress marker for proteins. The binding ability of endogenous substances (bilirubin and tryptophan) and drugs (warfarin and diazepam) to HSA purified from chronic liver disease patients were significantly suppressed but significantly improved by BCAA supplementation. Interestingly, the changes in this physiological function of HSA in chronic liver disease were correlated with the Cys-Cys34-HSA fraction. In conclusion, ESI-TOFMS is a suitable high throughput method for the rapid and sensitive quantification of Cys-Cys34-HSA in a large number of samples for evaluating oxidative stress related chronic disease progression or in response to a treatment.

Topics: Aged; Amino Acids, Branched-Chain; Bilirubin; Biomarkers; Chronic Disease; Cysteine; Diabetes Mellitus; Diazepam; Female; Glycation End Products, Advanced; Humans; Liver Cirrhosis; Male; Middle Aged; Models, Molecular; Oxidation-Reduction; Oxidative Stress; Protein Binding; Renal Insufficiency; Serum Albumin; Spectrometry, Mass, Electrospray Ionization; Tryptophan; Warfarin

Topics: Anticoagulants; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Male; Renal Insufficiency; Thromboembolism; Warfarin

The tale of dabigatran sounds some cautionary notes about proper critical appraisal of new randomised controlled trials,care in deciding on the generalisability of results, judicious screening of patients and lessons about the politics around increasingly lucrative drugs. The old lesson of caveat utilitor still holds: let the user beware!

Topics: Advertising; Anticoagulants; Antithrombins; Aspirin; Australia; Benzimidazoles; beta-Alanine; Cardiovascular Diseases; Dabigatran; Drug Interactions; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Patient Selection; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Renal Insufficiency; Research Design; Selection Bias; Stroke; Warfarin

Decreased glomerular filtration rate is an established risk factor for bleeding but there are limited data on its association with bleeding risk in well-controlled anticoagulated patients taking warfarin.. The aim was to investigate the relationship between glomerular filtration rate, major bleeding and thromboembolic complications in patients with tight anticoagulation control.. A cohort study of patients from a Swedish quality register for anticoagulation, including all the registered patients that received anticoagulation during 2008 in the anticoagulation center of Skåne University Hospital, Malmö. Key outcome measures were major bleeding and arterial or venous thrombosis during 2008. A total of 3536 patients (2875 treatment years) were included.. Total rates of 2.6 (2.0-3.2) bleeding events and 1.8 (1.3-2.3) thrombotic events per 100 treatment years were recorded (75 bleeding and 51 thromboembolic events). Data on estimated glomerular filtration rate were available in 3349 patients. Mean time in therapeutic range (international normalized ratio 2.0-3.0) was 74.5% (n=2894). Major bleeding events were significantly related to age and percentage of time with international normalized ratio >3.0 (P<0.001). Glomerular filtration rate levels <30 ml/min/1.73 m(2) were particularly associated with high risk of bleeding, especially in elderly patients. No correlation between glomerular filtration rate and thromboembolic events was seen.. With good anticoagulation control as measured by time in therapeutic range, patients had a relatively low risk for major bleeding if their renal function is normal. Despite good anticoagulation control, severely impaired kidney function is associated with a very high yearly risk of major bleeding events.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Female; Glomerular Filtration Rate; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Renal Insufficiency; Risk Factors; Thromboembolism; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Double-Blind Method; Humans; Morpholines; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Renal Insufficiency; Rivaroxaban; Secondary Prevention; Severity of Illness Index; Stroke; Thiophenes; Treatment Outcome; Warfarin

Matrix Gla protein (MGP) is an inhibitor of vascular calcification but its mechanism of action and pathogenic role are unclear. This was examined in cultured rat aortas and in a model of vascular calcification in rats with renal failure. Both carboxylated (GlaMGP) and uncarboxylated (GluMGP) forms were present in aorta and disappeared during culture with warfarin. MGP was also released into the medium and removed by ultracentrifugation, and similarly affected by warfarin. In a high-phosphate medium, warfarin increased aortic calcification but only in the absence of pyrophosphate, another endogenous inhibitor of vascular calcification. Although GlaMGP binds and inactivates bone morphogenic protein (BMP)-2, a proposed mediator of vascular calcification through up-regulation of the osteogenic transcription factor runx2, neither warfarin, BMP-2, nor the BMP-2 antagonist noggin altered runx2 mRNA content in aortas, and noggin did not prevent warfarin-induced calcification. Aortic content of MGP mRNA was increased 5-fold in renal failure but did not differ between calcified and noncalcified aortas. Immunoblots showed increased GlaMGP in noncalcified (5-fold) and calcified (20-fold) aortas from rats with renal failure, with similar increases in GluMGP. We conclude that rat aortic smooth muscle produces both GlaMGP and GluMGP in tissue-bound and soluble, presumably vesicular, forms. MGP inhibits calcification independent of BMP-2-driven osteogenesis and only in the absence of pyrophosphate, consistent with direct inhibition of hydroxyapatite formation. Synthesis of MGP is increased in renal failure and deficiency of GlaMGP is not a primary cause of medial calcification in this condition.

Topics: Animals; Anticoagulants; Aorta; Bone Morphogenetic Protein 2; Calcinosis; Calcium-Binding Proteins; Core Binding Factor Alpha 1 Subunit; Durapatite; Extracellular Matrix Proteins; Male; Matrix Gla Protein; Models, Biological; Muscle, Smooth, Vascular; Organ Culture Techniques; Osteogenesis; Protein Binding; Rats; Rats, Sprague-Dawley; Renal Insufficiency; RNA, Messenger; Up-Regulation; Uremia; Warfarin

Using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS), we determined incidence, prevalence, and outcomes among hemodialysis patients with atrial fibrillation. Cox proportional hazards models, to identify associations with newly diagnosed atrial fibrillation and clinical outcomes, were stratified by country and study phase and adjusted for descriptive characteristics and comorbidities. Of 17,513 randomly sampled patients, 2188 had preexisting atrial fibrillation, with wide variation in prevalence across countries. Advanced age, non-black race, higher facility mean dialysate calcium, prosthetic heart valves, and valvular heart disease were associated with higher risk of new atrial fibrillation. Atrial fibrillation at study enrollment was positively associated with all-cause mortality and stroke. The CHADS2 score identified approximately equal-size groups of hemodialysis patients with atrial fibrillation with low (less than 2) and higher risk (more than 4) for subsequent strokes on a per 100 patient-year basis. Among patients with atrial fibrillation, warfarin use was associated with a significantly higher stroke risk, particularly in those over 75 years of age. Our study shows that atrial fibrillation is common and associated with elevated risk of adverse clinical outcomes, and this risk is even higher among elderly patients prescribed warfarin. The effectiveness and safety of warfarin in hemodialysis patients require additional investigation.

Topics: Age Distribution; Aged; Anticoagulants; Atrial Fibrillation; Data Collection; Humans; Incidence; Middle Aged; Mortality; Prevalence; Renal Dialysis; Renal Insufficiency; Stroke; Treatment Outcome; Warfarin

In patients with kidney impairment, warfarin, a drug metabolized primarily by the cytochrome P-450 system, is initiated at similar doses and managed similarly as in the general medical population. Unfortunately, few data exist to guide dose adjustment in patients with decreased kidney function. Here, we determine the degree of warfarin dose reduction associated with kidney impairment and make recommendations for warfarin dosing.. Cross-sectional analysis.. Long-term warfarin users followed up at anticoagulation clinics (n = 980); 708 participants from the University of Alabama (UAB) and 272 participants from the University of Chicago (UIC).. No/mild (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2)), moderate (eGFR, 30-59 mL/min/1.73 m(2)), and severe (eGFR < 30 mL/min/1.73 m(2)) kidney impairment; CYP2C9 and VKORC1 genotype; age; race; sex; body mass; sociodemographic factors; smoking status; alcohol; vitamin K intake; comorbid conditions (eg, congestive heart failure); and drug interactions (eg, amiodarone and statins).. Warfarin dose (milligrams per day) was evaluated using linear regression after adjustment for clinical, demographic, and genetic factors.. Prevalences of moderate (31.8% and 27.6%) and severe kidney impairment (8.9% and 6.6%) were similar in the UAB and UIC cohorts. Warfarin dose requirements were significantly lower in patients with moderate and severe kidney impairment compared with those with no/mild kidney impairment in the UAB (P < 0.001) and UIC (P < 0.001) cohorts. Compared with patients with no/mild kidney impairment, patients with moderate kidney impairment required 9.5% lower doses (P < 0.001) and patients with severe kidney impairment required 19% lower doses (P < 0.001).. No measurement of warfarin, serum albumin, vitamin K, and coagulation factors; no evaluation of other markers (eg, cystatin).. Moderate and severe kidney impairment were associated with a reduction in warfarin dose requirements.

Topics: Aged; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cross-Sectional Studies; Cytochrome P-450 CYP2C9; DNA; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Genotype; Glomerular Filtration Rate; Humans; Male; Middle Aged; Mixed Function Oxygenases; Polymerase Chain Reaction; Polymorphism, Genetic; Prognosis; Prospective Studies; Renal Insufficiency; Severity of Illness Index; Thrombophilia; Vitamin K Epoxide Reductases; Warfarin

Topics: Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Infusions, Intravenous; Magnetic Resonance Angiography; Male; Renal Insufficiency; Renal Veins; Thrombolytic Therapy; Tissue Plasminogen Activator; Vena Cava, Inferior; Venous Thrombosis; Warfarin

In contrast to heparins and oral anticoagulants, anti IIa inhibitors (thrombin inhibitors) are able to directly inhibit the protease activity of thrombin and can thereby precisely control the blood coagulation process. Direct thrombin inhibitors are either biosimilars (r-hirudin) or synthetically produced substances (bivalirudin, argatroban, dabigatran). In 1997 r-hirudin was introduced into clinical practice, however due to its narrow therapeutic range and the necessity of drug monitoring it has not gained widespread clinical use by now. Since 2004 and 2005 the synthetic thrombin inhibitors bivalirudin and argatroban, respectively, are available. With dabigatran the first oral synthetic thrombin inhibitor followed in 2008. These four drugs can inhibit even clot bound thrombin and show low plasma protein binding. They differ in respect to route and duration of application as well as elimination from the body, thereby offering a precise inhibition of blood coagulation adjusted to the individual case and without danger of HIT II. These advantages shall be used and advanced by the development of further direct thrombin inhibitors.

Topics: Aged; Anticoagulants; Biotransformation; Coumarins; Female; Hemostasis; Heparin; Humans; International Normalized Ratio; Male; Middle Aged; Pharmacogenetics; Renal Insufficiency; Vitamin K; Warfarin

The aim of this analysis was to evaluate the roles of anemia, hypoalbuminemia, and renal impairment as independent predictors of bleeding in patients with nonvalvular atrial fibrillation (NVAF) receiving anticoagulation therapy with warfarin.. This was a previously published prospective, observational study conducted between November 1999 and July 2001. Patients with NVAF newly started on warfarin and referred to an anticoagulation clinic at a large university hospital (Northern General Hospital, Sheffield, United Kingdom), either at the time of hospital discharge or by their general practitioner, were eligible. Patients were divided into 2 groups: those aged <75 years; and those aged > or =75 years. Patients were seen at the clinic for an initial visit, and baseline information, including age, sex, employment status, medical history, and medication list, was obtained. Patients were also interviewed regarding episodes of bleeding (classified as minor bleeding events or major bleeding events) at the initial patient visit and by telephone every 4 to 6 weeks thereafter.. A total of 402 patients (mean [SD] age, 72.3 [10.3] years [range, 34-94 years]; 224 men [55.7%], 178 women [44.3%]) were included. Follow-up was complete for all patients (mean follow-up, 19.0 [8.1] months [range, 1.0-31.0 months]). A total of 107 minor and 11 major bleeding events were reported. Hypoalbuminemia was a significant predictor of all bleeding in patients aged <75 years (adjusted odds ratio [AOR] = 2.60; 95% CI, 1.26-5.33; P = 0.01), while renal impairment was a significant predictor in patients aged > or = 75 years (AOR = 2.65; 95% CI, 1.71-6.49; P = 0.01). After stratification by bleeding type, renal impairment was a significant predictor of major bleeding in patients aged > or = 75 years (AOR = 2.93; 95% CI, 1.03-9.58; P = 0.001). Anemia was not associated with bleeding.. Hypoalbuminemia and renal impairment were identified as patient-related predictive factors for bleeding, whereas anemia did not appear to increase this risk.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Anticoagulants; Atrial Fibrillation; Controlled Clinical Trials as Topic; Female; Follow-Up Studies; Hemorrhage; Humans; Hypoalbuminemia; Male; Middle Aged; Renal Insufficiency; Risk Factors; Warfarin

Hemodialysis complicated by heparin-induced thrombocytopenia (HIT) is a rare event requiring anticoagulation with direct-thrombin inhibitors. Contaminant calcific uremic arteriolopathy (calciphylaxis) further complicates this situation due to the possibility that warfarin anticoagulation may exacerbate skin necrosis. The authors report a patient with renal failure and calciphylaxis who developed HIT after starting hemodialysis. She was successfully treated with Argatroban.

Topics: Adult; Anticoagulants; Arginine; Calciphylaxis; Drug Contamination; Female; Heparin; Humans; Necrosis; Pipecolic Acids; Renal Dialysis; Renal Insufficiency; Skin Diseases; Sulfonamides; Thrombocytopenia; Warfarin

Low molecular weight heparins (LMWHs) are a rapidly growing class of anticoagulant drug. Their efficacy has been demonstrated in several clinical settings where they are rapidly becoming the anticoagulant of choice. Controlled clinical studies in patients with deep vein thrombosis, pulmonary embolism, and unstable angina have documented that the frequency of major hemorrhage is 0.5-4%. The purpose of the study was to determine the frequency of minor and major hemorrhage occurring in patients receiving anticoagulant doses of an LMWH (enoxaparin) during routine clinical practice. A prospective, observational study of consecutive patients receiving enoxaparin 1 mg/kg twice daily for at least 24 hours in five internal medicine wards of a university teaching hospital was performed. Five hundred forty-nine patients were studied. The mean age was 67.5+/-15.5 years and the mean duration of enoxaparin therapy was 3.8+/-1.5 days. Hemorrhage was documented in a total of 94 patients (17.3%). Major hemorrhage occurred in 14 patients (2.6%), injection-site hemorrhage occurred in 55 patients (10%), and minor hemorrhage (noninjection site) was documented in 25 patients (4.7%). There were two deaths attributed to hemorrhage. Patients with major hemorrhage were older than patients with minor or no hemorrhage (75.5+/-10.4 versus 66.8+/-15.2 years; p=0.03) and occurred in patients receiving enoxaparin for a longer period (5.14+/-3.8 days) than those with minor (4+/-2.5 days) or no hemorrhage (2.9+/-2.1 days). Major hemorrhage was significantly associated with impaired renal function, chronic liver disease, and concomitant treatment with warfarin or a proton pump inhibitor. Enoxaparin used in anticoagulant doses in unselected medical patients is not associated with more major hemorrhagic complications than observed in controlled clinical trials. Major hemorrhage may be more likely in older patients, in patients with chronic liver disease and impaired renal function, in patients receiving prolonged enoxaparin therapy, and in patients receiving warfarin or proton pump inhibitors.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Drug Evaluation; Enoxaparin; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Hospitals; Humans; Incidence; Liver Diseases; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Renal Insufficiency; Warfarin

Topics: Aged; Anemia; Anticoagulants; Diagnosis, Differential; Erythropoietin; Granulomatosis with Polyangiitis; Humans; Leg Ulcer; Male; Recombinant Proteins; Renal Insufficiency; Thrombosis; Treatment Outcome; Warfarin

Topics: Anticoagulants; Embolism; Embolism, Cholesterol; Humans; Pulmonary Embolism; Renal Insufficiency; Warfarin

Necrosis of skin and soft tissue as a complication of oral anticoagulation therapy is a rare condition with approximately 200 cases documented in the world. Coumadin-induced skin necrosis is a painful skin lesion, sudden, localized, initially erythematous or hemorrhagic, that becomes bullous and eventually culminates in gangrenous necrosis. It develops mainly in women around 50 years of age who are usually obese and have been treated for thrombophlebitis or pulmonary embolism. There seems to be a marked predilection for areas with increased subcutaneous fat content, such as breasts, thighs, and buttocks. The injury is so significant that plastic surgery is frequently required to repair the damaged tissue. The authors present four clinical cases of Coumadin necrosis, observed in two different institutions, and perform a literature review on the mechanisms that trigger the development of the disease. This condition still remains a diagnostic-therapeutic challenge.

Topics: Adult; Anticoagulants; Female; Humans; Middle Aged; Necrosis; Pulmonary Embolism; Renal Insufficiency; Skin; Thrombophlebitis; Warfarin

A 54-year-old man developed renal failure, with renal biopsy findings of diffuse mesangiolysis with severe endocapillary proliferation. Immunohistochemical studies revealed that CD3-CD56-CD57+ large granular lymphocytes were present predominantly within glomerular tufts. Intercellular adhesion molecule-1 was more preferentially expressed in the glomerular endothelial cells with severe endocapillary proliferation as compared to those without endocapillary proliferation. These findings suggest that CD57+ large granular lymphocytes caused glomerular endothelial injury by a cell-mediated cytolytic mechanism, resulting in the development of mesangiolysis and microaneurysm formation.

Topics: Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Biopsy; CD57 Antigens; Cyclophosphamide; Dipyridamole; Glomerular Mesangium; Humans; Immunoenzyme Techniques; Intercellular Adhesion Molecule-1; Male; Methylprednisolone; Microscopy, Electron; Microscopy, Fluorescence; Middle Aged; Renal Insufficiency; T-Lymphocyte Subsets; T-Lymphocytes; Warfarin