rivaroxaban and Kidney-Diseases

Drug transporters, metabolic enzymes, and renal clearance play significant roles in the pharmacokinetics of direct oral anticoagulants (DOACs). Recommendations for DOAC drug-drug interactions (DDIs) by the product labeling are limited to selected CYP3A4 and P-glycoprotein inhibitors and lack considerations for concomitant renal dysfunction.. This review focuses on: 1) current recommendations for the management of pharmacokinetic DOAC DDIs and the evidence used to support them; 2) alterations in DOAC exposure in the setting of concomitant DDIs and mild, moderate, and severe renal impairment; 3) clinical outcomes associated with this combination; and 4) expert recommendations for the management of pharmacokinetic DOAC DDIs. English-language, full-text articles on apixaban, dabigatran, rivaroxaban, and edoxaban with a publication date up to 30 September 2021 were retrieved from PubMed.. Given the lack of supporting clinical data, empiric dose adjustments based on pharmacokinetic data alone should be avoided. When a considerable increase in a DOAC exposure is anticipated, it may be advisable to use an alternative DOAC or anticoagulant from a different class. Future research on identification of DOAC therapeutic ranges and target patient populations is needed to inform clinical utility of DOAC level monitoring to guide the management of DDIs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Drug Interactions; Humans; Kidney Diseases; Pyridones; Rivaroxaban

To review current literature for target-specific oral anticoagulants (TSOACs) and provide critical analysis for dosing recommendations in special population groups.. A literature search was conducted in Medline (1996 to April week 2 2015) and Embase (1980 to 2015 week 16) using key terms dabigatran, rivaroxaban, apixaban, edoxaban, kidney diseases, liver diseases, elderly, obesity, and special populations.. Randomized controlled trials in English assessing efficacy and safety of TSOACs in healthy adults and special populations were selected for analysis.. Phase 3 trials for TSOACs predominately excluded patients with severe renal impairment or active liver disease. There were no exclusion criteria based on age, body weight or body mass index. Additional conclusions were made in special populations, including those with renal or liver impairment and obese and elderly patients, based on secondary analyses, pharmacokinetic, and pharmacodynamic studies.. Pharmacokinetic and pharmacodynamic changes associated special populations may alter clinical decision with regard to drug selection and dosing. It is valuable to understand the rationale for labeled dosing recommendations in nonvalvular atrial fibrillation and venous thromboembolism treatment and prevention, particularly in patients that fall into special population groups. Furthermore, the use of TSOACs is likely to increase as clinicians gain experience with these agents and additional TSOACs and indications are approved.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Dabigatran; Humans; Kidney Diseases; Liver Diseases; Obesity; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Elective Surgical Procedures; Emergencies; Factor Xa Inhibitors; Hemorrhage; Humans; Kidney Diseases; Morpholines; Orthopedic Procedures; Postoperative Complications; Premedication; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk; Rivaroxaban; Thiophenes; Thrombophilia; Vitamin K

Although highly effective, warfarin use is complicated by its unpredictable narrow therapeutic window, genetic heterogeneity in pharmacokinetic response, numerous food and drug interactions, and the need for regular international normalized ratio (INR) monitoring. Currently, several novel oral anticoagulant (NOAC) drugs (dabigatran, rivaroxaban, apixaban) are available on the market as alternatives to warfarin. These agents all feature more predictable pharmacodynamic and pharmacokinetic properties than warfarin. Additionally, the NOACs do not require routine monitoring of coagulation parameters, and have a relatively lower potential for interactions with drug, herb, and dietary constituents, which enhances the convenience of management for both patients and health professionals alike. However, there are other considerations regarding the use of NOACs that must be taken into account during management of therapy. In contrast to warfarin, most NOACs need dosage adjustments in renal impairment and are contraindicated in severe liver impairment, and there are no specific antidotes for treating NOAC-related over-anticoagulation. The more frequent dosing needed for NOACs may reduce adherence, especially in elderly patients with polypharmacy. Furthermore, NOACs, especially dabigatran, are not as well tolerated as warfarin in patients with gastrointestinal diseases. Overall, the availability of the NOACs has expanded the treatment armamentarium, but they are not without risk. Given the limited experience with the NOACs, their limited range of indications, and their cost, the characteristics of each anticoagulant must be carefully considered to carefully select the agent that will provide the optimal risk/benefit profile in the individual patient.

Topics: Administration, Oral; Aging; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Complementary Therapies; Dabigatran; Drug Interactions; Drug Monitoring; Humans; International Normalized Ratio; Kidney Diseases; Liver Diseases; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Sex Factors; Stroke; Thiophenes; Warfarin

Patients with renal impairment are at higher risk of thrombosis and bleeding than those with normal renal function. The optimal rivaroxaban dose for thromboprophylaxis in acutely ill medical patients with renal impairment is unknown. MARINER and MAGELLAN were multicenter, randomized clinical trials of rivaroxaban in acutely ill medical patients. Efficacy and safety outcomes in patients with renal impairment in MARINER (7.5 mg once daily) were compared with those in patients with normal renal function in MARINER (10 mg once daily) and in a subpopulation of MAGELLAN that excluded patients at high risk for bleeding at baseline (10 mg once daily). Compared with enoxaparin/placebo in the MAGELLAN subpopulation, the relative risk (RR) of symptomatic venous thromboembolism (VTE) and VTE-related death with rivaroxaban 10 mg in patients with renal impairment (RR = 0.62; 95% confidence interval [CI] 0.27-1.44) was similar to that in those with normal renal function (RR = 0.78; 95% CI 0.44-1.40), while in MARINER, the 7.5 mg dose did not reduce the risk in patients with renal impairment (hazard ratio = 1.00; 95% CI 0.52-1.92). Major bleeding with rivaroxaban 10 mg once daily was higher in patients with renal impairment than in those with normal renal function in MAGELLAN (1.54% vs. 0.98%) and in the MAGELLAN subpopulation (0.94% vs. 0.61%). At a dose of 10 mg once daily, rivaroxaban is effective for thromboprophylaxis in acutely ill medical patients with impaired or normal renal function. The safety of this regimen is enhanced without loss of efficacy by excluding patients at high risk for bleeding, but not by using a reduced-dose strategy. TRIAL REGISTRATION:  ClinicalTrials.gov identifiers: NCT00571649 for the MAGELLAN trial, NCT02111564 for the MARINER trial.

Topics: Acute Disease; Aged; Anticoagulants; Double-Blind Method; Enoxaparin; Female; Hemorrhage; Humans; Incidence; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Risk Factors; Rivaroxaban; Thrombosis; Treatment Outcome; Venous Thromboembolism

A 34-year-old Japanese woman with systemic lupus erythematosus (SLE) was admitted to our hospital for exacerbation of renal dysfunction, hemolytic anemia and thrombocytopenia. Twenty-two years before admission, she was diagnosed with SLE. Eight years before, lupus anticoagulant (LAC) positivity was detected without any thrombotic findings. Fourteen months before, renal function started to worsen. Three months before, unprovoked left leg swelling appeared. She was diagnosed with deep vein thrombosis (DVT) by ultrasonography. Blood examination revealed mild anemia, thrombocytopenia, and renal dysfunction. Rivaroxaban was started after which the left leg swelling subsided. When she was referred to our hospital, LAC was positive, but hypocomplementemia nor elevation of serum anti-double-stranded DNA antibodies was detected. Renal biopsy showed acute and chronic thrombotic microangiopathy (TMA) without concurrent lupus nephritis. Brain magnetic resonance imaging showed new small multiple cerebral infarcts. Antiphospholipid antibody syndrome (APS), causing renal TMA, new cerebral infarction, and DVT was diagnosed. Rivaroxaban was changed to warfarin. Two months after admission, renal impairment improved, and the complete disappearance of DVT and brain infarcts was confirmed. This case suggests that warfarin may be more effective than direct oral anticoagulants in the treatment of APS-associated renal TMA.

Topics: Adult; Antiphospholipid Syndrome; Female; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Rivaroxaban; Thrombotic Microangiopathies; Treatment Outcome; Warfarin

The EXPAND Study demonstrated the effectiveness and safety of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) in routine clinical practice in Japan. This sub-analysis was conducted to reveal the effectiveness and safety of rivaroxaban in Japanese NVAF patients according to baseline creatinine clearance (CrCl) levels and rivaroxaban doses in the EXPAND Study. We examined 6806 patients whose baseline CrCl data were available and classified them into 2 groups: normal renal function group with CrCl ≥ 50 mL/min (n = 5326, 78%) and renal dysfunction group with CrCl < 50 mL/min (n = 1480, 22%). In the normal renal function group, 1609 (30%) received 10 mg/day (under-dose), while in the renal dysfunction group, 108 (7%) received 15 mg/day (over-dose). In the normal renal function group, under-dose of rivaroxaban was associated with higher all-cause mortality, while in the renal dysfunction group, over-dose was associated with higher incidence of major bleeding. In contrast, the incidence of stroke or systemic embolism was not different between the 2 groups regardless of the dose of rivaroxaban. In the propensity score matched analysis to adjust the difference in characteristics according to doses of rivaroxaban, the incidences of clinical outcomes were comparable between the 2 dose groups in both renal function groups. These results indicate that the dose of rivaroxaban should be reduced depending on the renal function, considering the balance between risks of bleeding and ischemia.

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Factor Xa Inhibitors; Hemorrhage; Humans; Ischemic Stroke; Kidney Diseases; Rivaroxaban; Treatment Outcome

Patients with nonvalvular atrial fibrillation (NVAF) and type 2 diabetes are at risk of kidney, limb, and ophthalmic complications. We evaluated the rate of these complications and death in patients with NVAF and type 2 diabetes prescribed rivaroxaban or warfarin.. We analyzed Optum de-Identified electronic health record (EHR) data from 11/2010-12/2019. We included adults with NVAF and T2D newly initiated on rivaroxaban or warfarin with ≥12 months of prior EHR activity. Patients with another indication for anticoagulation, valve disease, history of end-stage renal disease, major adverse limb events (MALE), diabetic retinopathy or pregnancy were excluded. We evaluated the incidence rate of developing a composite outcome of >40% decrease in estimated glomerular filtration incidence rate (eGFR) from baseline, eGFR < 15 mL/minute/1.73 m2, need for dialysis or kidney transplant, MALE, diabetic retinopathy or death. Overlap weighting was used to balance baseline characteristics between cohorts while preserving sample size. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted Cox regression.. We included 24,912 rivaroxaban and 58,270 warfarin users. The mean ± standard deviation (SD) CHA2DS2VASc score was 4.3 ± 1.5 and modified HASBLED score was 1.5 ± 0.8. Thirty percent of rivaroxaban patients were started on 15 mg once daily, with the rest prescribed 20 mg once daily. Warfarin patients had a mean time in therapeutic range of 47 ± 28%. Patients were followed for a mean of 2.89 ± 1.95 years. Rivaroxaban was associated with a reduced hazard of the composite outcome (HR = 0.93, 95%CI = 0.91-0.95; absolute risk reduction = 1.97 events per 1000 patient-years; number needed-to-treat = 51) versus warfarin. Rivaroxaban was also associated with significant reductions in the relative hazard of > 40% decrease in eGFR from baseline (HR = 0.96), need for dialysis or renal transplant (HR = 0.81), and limb revascularization or major amputation (HR = 0.85). Death occurred at a lower incidence rate with rivaroxaban (HR = 0.92, 95%CI = 0.89-0.95).. Rivaroxaban was associated with reduced incidence rates of kidney and limb complications, and death in NVAF patients with type 2 diabetes compared to warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Diabetes Mellitus, Type 2; Electronic Health Records; Eye Diseases; Humans; Kidney; Kidney Diseases; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

To investigate the decline of estimated glomerular filtration rate (eGFR) in patients with atrial fibrillation (AF) treated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs).. Multicentre prospective cohort study including 1667 patients with nonvalvular AF. The eGFR was assessed by the CKD-EPI formula at baseline and during follow-up. The primary endpoint of the study was the median annual decline of eGFR according to VKA (n = 743) or NOAC (n = 924) use. As secondary endpoints, we analysed the transition to eGFR <50 mL/min/1.73 m. Median age was 73.7 ± 9.1 years and 43.3% were women. VKA-treated patients showed an eGFR decline of -2.11 (interquartile range [IQR] -5.68/-0.62), which was -0.27 (IQR -9.00/4.54, P < 0.001 vs VKAs), -1.21 (IQR -9.98/4.02, P = 0.004 vs VKAs) and -1.32 (IQR -8.70/3.99, P = 0.003 vs VKAs) in patients on dabigatran, rivaroxaban and apixaban, respectively. Transition to eGFR <50 mL/min/1.73 m. Patients prescribed NOACs showed a lower decline of renal function compared to those prescribed VKAs. This effect was partially lost in patients with diabetes.

Topics: Administration, Oral; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies; Rivaroxaban; Stroke

Recommended rivaroxaban doses for stroke prevention in atrial fibrillation (SPAF) are 20 and 15 mg/day in patients with normal and reduced renal function, respectively, but lower doses (15 and 10 mg) have been tested and approved in Japan. It is not known whether 15 and 10 mg rivaroxaban are appropriate in other Asian populations. This study compared the anti-Factor Xa (FXa) activity of 20 and 15 mg rivaroxaban in Thai patients with normal renal function and 15 and 10 mg rivaroxaban in patients with reduced renal function.Methods and Results:Sixty non-valvular atrial fibrillation patients receiving rivaroxaban (mean [±SD] age 69.3±9.1 years, mean creatinine clearance 59.2±22.7 mL/min) were enrolled. The anti-FXa activity of standard rivaroxaban and Japan-specific doses was measured at peak and trough concentrations. Median anti-FXa activity at peak concentrations was significantly higher for the standard than Japan-specific dose. Median anti-FXa activity measured at the trough was significantly higher for the standard dose only in those with impaired renal function. A higher proportion of patients receiving the Japan-specific rather than standard dose had anti-FXa activity at peak concentrations within the expected range (87.7% vs. 64.4%; P=0.001). One-third of those receiving the standard dose had anti-FXa activity higher than the expected range.. A significantly higher proportion of Thai patients receiving the Japan-specific dose of rivaroxaban had anti-FXa activity at peak concentrations within the expected range.

Topics: Aged; Asian People; Atrial Fibrillation; Drug Dosage Calculations; Drug Monitoring; Factor Xa Inhibitors; Female; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies; Rivaroxaban; Stroke; Thailand; Treatment Outcome

In Japanese surveillance in an early phase after the approval of rivaroxaban, inappropriate underdose was frequently utilized. The aim of this study was to describe the prevalence and predictors of the inappropriate usage of rivaroxaban in a single-center, cardiovascular-specialized hospital. Consecutive 661 non-valvular atrial fibrillation (NVAF) patients treated with rivaroxaban between 2012 and 2017 were recruited. After excluding 30 patients without assessment of creatinine clearance (CCr), the proportion and predictors of inappropriate underdose were analyzed. Additionally, patient outcomes, including thromboembolism (ischemic stroke or systemic embolism) and major bleeding, were determined. In patients with CCr ≥ 50 mL/min (n = 532) and < 50 mL/min (n = 98), inappropriate underdose and overdose were used in 123 (23%) and 8 (8%), respectively. The predictors of inappropriate underdose (in patients with CCr ≥ 50 mL/min) were CCr [50-63 mL/min (the lowest tertile) compared to ≥ 64 mL/min], age ( ≥ 75 years), female gender, prescription of antiplatelet, and coexistence of heart failure. Although PT under rivaroxaban was lower in patients with inappropriate underdose than in those with an appropriate dose, no significant increase in the incidence of thromboembolism or major bleeding was observed within the mean follow-up of 683 days. Inappropriate underdose of rivaroxaban was frequently observed for NVAF patents even in a cardiovascular hospital, particularly in patients with CCr adjacent to the dose reduction criteria. The responses of PT and the incidence of adverse outcomes under an inappropriate dose of rivaroxaban should be further investigated.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Creatinine; Drug Utilization; Factor Xa Inhibitors; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Inappropriate Prescribing; Japan; Kidney; Kidney Diseases; Male; Middle Aged; Practice Patterns, Physicians'; Prothrombin Time; Risk Factors; Rivaroxaban; Stroke; Thromboembolism; Time Factors; Treatment Outcome

To determine discontinuation rates, patterns of use and predictors of discontinuation of non-vitamin K antagonist oral anticoagulants (NOACs) among patients with non-valvular atrial fibrillation (NVAF) in the first year of therapy.. Population-based cohort study.. UK primary care.. 11 481 patients with NVAF and a first prescription (index date) for apixaban, dabigatran or rivaroxaban (January 2012 to December 2016) with at least 1 year of follow-up and at least one further NOAC prescription in the year following the index date were identified. 1 year rates and patterns of discontinuation were described.. Outcome measures were the percentage of patients who, in the first year from starting NOAC therapy, discontinued with their oral anticoagulant (OAC) therapy (discontinuation was defined as a gap in OAC therapy of >30 days); switched OAC within 30 days; discontinued and reinitiated OAC therapy. Predictors of discontinuation were also evaluated.. 1 year discontinuation rates according to the index NOAC were 26.1% for apixaban, 40.0% for dabigatran and 29.6% for rivaroxaban. Reinitiation rates were 18.1% for apixaban, 21.7% for dabigatran and 17.3% for rivaroxaban, and switching rates were 2.8% for apixaban, 8.8% for dabigatran and 4.9% for rivaroxaban. More than 93% of reinitiations were with the index NOAC. Patients starting on dabigatran were more likely to switch OAC therapy than those starting on apixaban; ORs 4.28 (95% CI 3.24 to 5.65) for dabigatran and 1.89 (95% CI 1.49 to 2.39) for rivaroxaban. Severely reduced renal function was a predictor of any discontinuation, OR 1.77 (95% CI 1.28 to 2.44).. While the majority of patients with NVAF in the UK initiating NOAC treatment received continuous therapy in the first year of treatment, a substantial proportion of patients experienced gaps in treatment leaving them less protected against thromboembolism during these periods.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Humans; Kidney Diseases; Male; Medication Adherence; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; United Kingdom

Steady-state plasma concentrations of anticoagulants and the time since the previous administration in mainly outpatients with atrial fibrillation administered standard or reduced doses were analyzed for 110 elderly Japanese subjects (mean age, 76 years) treated with apixaban (2.5 or 5.0 mg twice daily), dabigatran etexilate (110 or 150 mg twice daily), edoxaban (30 or 60 mg once daily) or rivaroxaban (10 or 15 mg once daily) at one general hospital. The pharmacokinetics in patients treated with standard and reduced doses of the four anticoagulants using liquid chromatography-tandem mass spectrometry was compared with the concentration ranges estimated using physiologically based pharmacokinetic modeling. Reduced doses of anticoagulants resulted in relatively small pharmacokinetic variations compared with the standard dose. Statistical analyses revealed that renal impairment is likely not the sole determinant factor for high plasma concentrations of apixaban, dabigatran, edoxaban and rivaroxaban. Patients with atrial fibrillation should be treated with the correct doses of oral anticoagulants as specified in the package inserts (e.g. reduced doses for elderly patients, patients with low body weights and in combination with P-glycoprotein inhibitor drugs) to avoid excessive or insufficient doses of direct oral anticoagulants.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Dose-Response Relationship, Drug; Female; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles

Nonvalvular atrial fibrillation (NVAF) is highly prevalent and increases the risks of cardiovascular events. In a recent subgroup analysis, treatment response was shown to vary for patients exhibiting worsening renal function (WRF) on-treatment. It is important to understand the cost-effectiveness of novel oral anticoagulant (NOAC) use in this population.. A cost-effectiveness analysis (CEA) was conducted using a Markov model to determine whether NOAC rivaroxaban treatment is cost-effective relative to warfarin in NVAF patients with on-treatment WRF. Input parameters were sourced from clinical literature including a multicenter clinical trial and subgroup analysis. We studied elderly US male patients at increased risk for stroke (CHADS. The remaining lifetime use of rivaroxaban is associated with 5.69 QALYs at a cost of $66,075 per patient, while warfarin produced 5.22 QALYs with costs of $78,504 per patient. At a willingness-to-pay (WTP) of $150,000 per QALY, incremental net monetary benefits (INMB) per patient are $83,590. In our population, treatment with warfarin was dominated by rivaroxaban in 99.4% of 10,000 simulations.. Rivaroxaban is likely a dominant treatment over warfarin in elderly US male NVAF patients exhibiting WRF, providing increased QALYs at a decreased overall cost. Application of these findings may require healthcare providers to predict which patients are likely to exhibit WRF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Factor Xa Inhibitors; Humans; Kidney Diseases; Male; Rivaroxaban; Treatment Outcome; Warfarin

Topics: Aspirin; Factor Xa Inhibitors; Humans; Kidney Diseases; Rivaroxaban; Vascular Diseases

Information on utilization of oral anticoagulants (OACs) in nursing homes is scarce. This study aimed to (i) describe OAC use in German nursing home residents, (ii) examine factors influencing whether treatment is initiated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) and (iii) assess which conditions predict switching to NOAC instead of continuing VKA.. Using claims data (2010-2014), we studied a cohort of new nursing home residents aged ≥65 years receiving OAC. Further, OAC use in patients with atrial fibrillation (AF) was examined over the years.. Overall, 16 804 patients (median age: 85 years, 75% female, 44% with renal disease) were included. The majority received phenprocoumon as first OAC (58.0%), followed by rivaroxaban (28.1%). Over the study period, NOAC use increased substantially. Initiating NOAC instead of VKA was predicted by a previous stroke (adjusted odds ratio: 1.76; 95% confidence interval: 1.49-2.08). In contrast, renal disease predicted VKA initiation (0.66; 0.59-0.75) as did the presence of a prosthetic heart valve. Switching from VKA to NOAC was predicted by a stroke (2.55; 2.00-3.24), bleeding events and a recent hospitalization. During 2010-2014, the proportion of AF patients with a CHADS2 score ≥2 receiving OAC increased from 27% to 46%.. NOACs are increasingly used in German nursing homes, both for initial anticoagulation but also in VKA pre-treated patients. Switching from VKA to NOAC was substantially influenced by aspects such as intended higher effectiveness and safety but probably also practicability due to less blood monitoring.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Drug Monitoring; Female; Germany; Hemorrhage; Humans; Kidney Diseases; Male; Nursing Homes; Phenprocoumon; Rivaroxaban; Stroke; Vitamin K

Rivaroxaban (RXA) is a direct oral factor Xa (Xa) antagonist with a short half-life and a fast onset and offset of effect. Before elective surgery, discontinuation is recommended with an interval of at least > 24 hours. In clinical practice, this is, however, not always sufficient to achieve a residual RXA plasma concentration deemed appropriate for surgery, defined as ≤ 50 mcg/L. Our study aimed at identifying factors associated with a higher-than-expected residual RXA plasma concentration in a large group of real-life patients.. This retrospective single-centre study included all patients taking RXA between 2012 and 2016 where RXA plasma concentration was determined by pharmacodynamic anti-Xa assay (518 measurements in 368 patients). Medical records were reviewed. Residual RXA plasma concentrations were then compared with expected values according to a pharmacokinetic model.. In our group of real-life patients, impaired kidney function (GFR < 60 mL/min) and co-medication with amiodarone were independently associated with higher-than-expected residual RXA plasma concentrations. In these patients, standard intervals of RXA discontinuation may not always be sufficient before elective surgery and routine pre-operative determination of the residual RXA concentration could be advisable.

Topics: Administration, Oral; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Blood Coagulation; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Factor Xa Inhibitors; Female; Glomerular Filtration Rate; Half-Life; Humans; Kidney; Kidney Diseases; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Polypharmacy; Preoperative Care; Retrospective Studies; Risk Factors; Rivaroxaban; Switzerland

Lifelong oral anticoagulation, either with warfarin or a non-vitamin K antagonist oral anticoagulant (NOAC), is indicated for stroke prevention in most patients with atrial fibrillation (AF). Emerging evidence suggests that NOACs may be associated with better renal outcomes than warfarin.. This study aimed to compare 4 oral anticoagulant agents (apixaban, dabigatran, rivaroxaban, and warfarin) for their effects on 4 renal outcomes: ≥30% decline in estimated glomerular filtration rate (eGFR), doubling of the serum creatinine level, acute kidney injury (AKI), and kidney failure.. Using a large U.S. administrative database linked to laboratory results, the authors identified 9,769 patients with nonvalvular AF who started taking an oral anticoagulant agent between October 1, 2010 and April 30, 2016. Inverse probability of treatment weighting was used to balance more than 60 baseline characteristics among patients in the 4 drug cohorts. Cox proportional hazards regression was performed in the weighted population to compare oral anticoagulant agents.. The cumulative risk at the end of 2 years for each outcome was 24.4%, 4.0%, 14.8%, and 1.7% for ≥30% decline in eGFR, doubling of serum creatinine, AKI, and kidney failure, respectively. When the 3 NOACs were pooled, they were associated with reduced risks of ≥30% decline in eGFR (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.66 to 0.89; p < 0.001), doubling of serum creatinine (HR: 0.62; 95% CI: 0.40 to 0.95; p = 0.03), and AKI (HR: 0.68; 95% CI: 0.58 to 0.81; p < 0.001) compared with warfarin. When comparing each NOAC with warfarin, dabigatran was associated with lower risks of ≥30% decline in eGFR and AKI; rivaroxaban was associated with lower risks of ≥30% decline in eGFR, doubling of serum creatinine, and AKI; however, apixaban did not have a statistically significant relationship with any of the renal outcomes.. Renal function decline is common among patients with AF treated with oral anticoagulant agents. NOACs, particularly dabigatran and rivaroxaban, may be associated with lower risks of adverse renal outcomes than warfarin.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Atrial Fibrillation; Creatinine; Dabigatran; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; International Normalized Ratio; Kidney Diseases; Male; Middle Aged; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Treatment Outcome; United States; Warfarin

Topics: Aged; Anticoagulants; Drug Substitution; Factor Xa Inhibitors; Humans; Kidney Diseases; Male; Necrosis; Rivaroxaban; Skin; Skin Diseases; Warfarin; Wound Healing

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Contraindications; Dabigatran; Drug Interactions; Drug Monitoring; Drug Substitution; Female; Hemorrhage; Humans; Kidney Diseases; Kidney Function Tests; Male; Morpholines; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Thrombophilia

New oral anticoagulants (NOAC) are becoming available as alternatives to warfarin to prevent systemic embolism in patients with non-valvular atrial fibrillation and for the treatment and prevention of venous thromboembolism. An in-depth understanding of their pharmacology is invaluable for appropriate prescription and optimal management of patients receiving these drugs should unexpected complications (such as bleeding) occur, or the patient requires urgent surgery. The Australasian Society of Thrombosis and Haemostasis has set out to inform physicians on the use of the different NOAC based on current available evidence focusing on: (i) selection of the most suitable patient groups to receive NOAC, (ii) laboratory measurements of NOAC in appropriate circumstances and (iii) management of patients taking NOAC in the perioperative period, and strategies to manage bleeding complications or 'reverse' the anticoagulant effects for urgent invasive procedures.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Coagulation Tests; Blood Loss, Surgical; Contraindications; Dabigatran; Drug Interactions; Drug Monitoring; Drug Substitution; Elective Surgical Procedures; Emergencies; Hematoma, Epidural, Spinal; Hemorrhage; Humans; Kidney Diseases; Liver Diseases; Morpholines; Patient Selection; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thrombophilia

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Drug Interactions; Hemorrhage; Humans; Kidney Diseases; Morpholines; Pyridines; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Topics: Administration, Oral; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Biomarkers; Chronic Disease; Creatinine; Dabigatran; Fibrinolytic Agents; Glomerular Filtration Rate; Humans; Incidence; Kidney; Kidney Diseases; Morpholines; Netherlands; Patient Selection; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Severity of Illness Index; Thiophenes