Comparison of effectiveness and safety of sodium polystyrene sulfonate and sodium zirconium cyclosilicate for treatment of hyperkalemia in hospitalized patients.

PURPOSE: Potassium binders are frequently utilized for the treatment of hyperkalemia in hospitalized patients; however, there is limited data directly comparing individual agents. The purpose of this study was to compare the effectiveness and safety of sodium polystyrene sulfonate (SPS) and sodium zirconium cyclosilicate (SZC) for hyperkalemia treatment in hospitalized patients. METHODS: This retrospective cohort study evaluated adult patients who were admitted within a 7-hospital health system and received SPS or SZC for a serum potassium level greater than 5.0 mEq/L. Patients receiving dialysis prior to SPS/SZC administration, those receiving other potassium-lowering medications within 6 hours prior to blood sampling for a repeat potassium level, and those started on kidney replacement therapy prior to sampling for a repeat potassium level were excluded. RESULTS: Following evaluation of 3,903 patients, the mean reduction in serum potassium 4 to 24 hours after binder administration was 0.96 mEq/L with SPS and 0.78 mEq/L with SZC (P < 0.0001). The median dose of SPS was 30 g (interquartile range [IQR], 15-30 g) while the median (IQR) dose of SZC was 10 g (10-10 g). Resolution of hyperkalemia within 24 hours was achieved in a higher percentage of patients with use of SPS (74.9%) versus SZC (68.8%) (P < 0.001). CONCLUSION: One of the largest comparisons of SPS and SZC conducted to date, this study demonstrated the effectiveness and safety of both agents. While a statistically greater reduction in serum potassium was observed with use of SPS, there was significant dosing variability among agents that limited the ability to directly compare specific doses. Further investigation is needed to determine the optimal dose of each agent for acute hyperkalemia management. This data will inform clinical decisions about the choice of potassium binder for acute hyperkalemia.

Evaluation of outcomes with apixaban use for venous thromboembolism in hospitalized patients with end-stage renal disease receiving renal replacement therapy.

While direct oral anticoagulants (DOACs) received expanded labeling for use in atrial fibrillation (AF) for end-stage renal disease (ESRD) based on pharmacokinetic trials, little data exist regarding the use of DOACs for venous thromboembolism (VTE) in ESRD patients requiring renal replacement therapy (RRT). This retrospective, descriptive cohort study evaluated adult patients with a diagnosis of ESRD on RRT and with a VTE diagnosis receiving apixaban therapy prior to or during admission. The primary outcome was to identify major bleeding events within 72 h of last apixaban dose administration. Secondary outcomes included new VTE while on apixaban, appropriateness of anticoagulation regimen with regards to FDA labeled dosing and frequency, anticoagulation regimen adjustments, and factor Xa inhibitor-specific anti-Xa levels if available. A total of 68 patients met criteria for inclusion in the final analysis. Major bleeding events occurred in 13.2% of patients receiving apixaban within the last 72 h. Recurrent thrombosis occurred in 7.4% of patients. The use of apixaban for VTE in patients with ESRD on RRT led to a higher risk of bleeding compared to that of landmark trials. Therefore, apixaban use should occur following shared decision making especially if there is no contraindication to warfarin.

Evaluation of Anti-Xa Apixaban and Rivaroxaban Levels With Respect to Known Doses in Relation to Major Bleeding Events.

BACKGROUND: Although not routinely recommended, anti-Xa level monitoring for apixaban or rivaroxaban may be useful in certain clinical scenarios. There are currently no laboratory standards, therapeutic ranges, or proven correlation between anti-Xa levels and clinical outcomes. OBJECTIVE: This study describes the utilization, application, and association of anti-Xa levels with clinical outcomes in patients receiving apixaban or rivaroxaban. METHODS: This retrospective, descriptive study included adult inpatients within the Houston Methodist System on apixaban or rivaroxaban with at least one anti-Xa level ordered subsequent to administered doses. The primary endpoint was major bleeding according to International Society on Thrombosis and Haemostasis criteria. Secondary endpoints included reasons for anti-Xa level ordering, anti-Xa levels at different time intervals post-dose, and thrombotic events. Pre-specified subgroup analyses were performed to further evaluate the primary endpoint. RESULTS: The study population consisted of 169 patients and 234 anti-Xa levels. Twenty-nine levels were obtained in context of major bleeding. The majority of levels were not drawn as peak levels 2-4 hours post-dose, however remained quantifiable above typical observed levels within this timeframe and well beyond 24 hours post-dose. Patient characteristics with major bleeding included elderly age, acute renal impairment, and low body weight. At least 14 unique reasons for anti-Xa level ordering were identified. Twenty-nine levels were associated with thrombotic events. CONCLUSION: Anti-Xa levels may be useful for assessment of current drug concentrations, immediate safety of therapy, and guidance for possible clinical interventions. Dose titration and reversal therapies based on anti-Xa level results in major bleeding warrant further research.

Apixaban and Rivaroxaban Anti-Xa Level Monitoring Versus Standard Monitoring in Hospitalized Patients With Acute Kidney Injury.

BACKGROUND: Oral direct factor Xa inhibitors (FxaIs) are renally eliminated; thus, acute kidney injury (AKI) may increase the risk for drug accumulation and bleeding. There is minimal data describing the effects of AKI on FxaI anti-Xa levels or clinical outcomes. OBJECTIVE: To compare anti-Xa level monitoring with standard monitoring in patients who experience AKI on apixaban or rivaroxaban. METHODS: This retrospective study included patients admitted within a large hospital system from May 2016 to October 2020. Patients were included if they received apixaban or rivaroxaban prior to AKI. Patients were stratified into 1 of 2 groups: those with anti-Xa level monitoring or those who received standard monitoring. The primary outcome was major bleeding as defined by the International Society of Thrombosis and Haemostasis. RESULTS: A total of 196 patients were included in the final analysis. Major bleeding occurred in 2 patients who received anti-Xa level monitoring, compared with 14 patients who received standard monitoring (2.1% vs 14%; P < 0.01). Variables identified as predictors of major bleeding included a documented history of liver disease (adjusted odds ratio = 3.17; 95% CI = 1.04-9.67; P = 0.04) and antiplatelet use (adjusted odds ratio = 4.18; 95% CI = 1.28-13.7; P = 0.02). CONCLUSION AND RELEVANCE: This is the first study to demonstrate that anti-Xa level monitoring was associated with a significant reduction in major bleeding compared with standard monitoring in patients with AKI who received apixaban or rivaroxaban. The optimal management of antithrombotic medications in patients with AKI and recent exposure to an FxaI requires further investigation.

Evaluating Time to In-Hospital Venous Thromboembolism in Obese Patients.

BACKGROUND: Currently, no consensus approach exists for optimal venous thromboembolism (VTE) prophylaxis in obese (BMI ≥30 kg/m2) patients. Time to development of in-hospital VTE is not well studied. OBJECTIVE: This study evaluates time to in-hospital VTE in obese patients. METHODS: A single-center, retrospective study evaluated obese patients that developed an in-hospital VTE. Patients were categorized into 3 BMI groups: 30 to 34.9 (group 1), 35 to 39.9 (group 2), and ≥40 (group 3) kg/m2. The primary end point compared time to VTE between the groups. RESULTS: A total of 246 patients were included, and time to VTE was similar between the groups, 8 (group 1) versus 8 (group 2) versus 9 days (group 3); P = .38. Secondary outcomes showed time to VTE was shorter in acute care versus ICU patients (7.5 vs 10 days; P = .01), nonsurgical versus surgical patients (6 vs 9 days; P = .004), and no prophylaxis versus mechanical plus pharmacologic prophylaxis (4.5 vs 9 days; P < .001). CONCLUSIONS: BMI category did not significantly impact time to in-hospital VTE. This study provides insight into the timing of in-hospital VTE in obese patients. The differences in prophylactic strategies highlight the importance of optimized prophylaxis.

Evaluation of characteristics and dosing regimens in patients with new or recurrent thrombosis on apixaban and rivaroxaban.

Direct factor Xa inhibitors, such as apixaban and rivaroxaban, are widely used for treatment and prevention of venous thromboembolism; however, recent cases of therapeutic failure have been reported. Potential risk factors associated with therapeutic failure such as dose deviations outside of package labeling recommendations, and the use of direct factor Xa-specific inhibitor levels to guide clinical decision making continue to be areas of further investigation. Our study aimed to describe characteristics and dosing regimens in patients on apixaban or rivaroxaban who experienced a new or recurrent thrombosis. We performed a retrospective chart review on 190 patients on either apixaban or rivaroxaban presenting to our institution with new or breakthrough thromboembolism. Evaluation of prescribed anticoagulation regimens compared to package labeling recommendations, direct factor Xa inhibitor-specific anti-Xa levels, anticoagulation interruptions, use of parenteral bridge anticoagulation, final anticoagulation regimen disposition, and thrombosis-associated mortality were recorded. In patients presenting with breakthrough thromboembolism, 78% were on a regimen that matched package labeling recommendations. Anti-Xa levels were documented in 66 patients, the majority of which fell within institutional expected ranges at time of thrombosis. Therapy interruptions immediately prior to thrombosis were observed in 22% of patients and 21% of those patients received parenteral anticoagulation during interruption. Upon discharge, 46% of patients continued the same anticoagulation regimen with no changes. The mortality rate was 6%. In patients who present with new thromboembolism on apixaban or rivaroxaban, a thorough review of risks and benefits should be conducted to mitigate future risk of recurrent thrombosis.

Apixaban and rivaroxaban anti-Xa level utilization and associated bleeding events within an academic health system.

BACKGROUND: Oral factor Xa inhibitors (FXaI) can be administered in fixed doses without the need for routine laboratory monitoring. Anti-Xa assays can estimate anticoagulant effect for specific FXaI's. The aim of this study was to characterize anti-Xa levels in patients taking apixaban or rivaroxaban with major bleeding events. METHODS: Apixaban and rivaroxaban anti-Xa assays ordered within our hospital system from May 2016 to September 2019 were evaluated. The primary outcome was major bleeding events defined by International Society of Thrombosis and Haemostasis criteria. Median anti-Xa levels for each FXaI were calculated for those with and without major bleeding, as well as those who did and did not receive reversal agents. RESULTS: A total of 606 anti-Xa levels were analyzed. There were 146 major bleeding events documented, with the most common site being intracranial (63%). Median anti-Xa levels in patients with and without major bleeding were similar, whereas those on apixaban therapy who received reversal agents typically had higher anti-Xa levels (73 ng/mL vs. 153 ng/mL, p = 0.0019). Factors significantly associated with increased odds of bleeding were an age > 80 years, inappropriately high dosing regimens, and modest anti-Xa levels (100-300 ng/mL) for rivaroxaban specifically. CONCLUSIONS: Older age and inappropriately high dosing regimens were associated with major bleeding in patients taking apixaban and rivaroxaban. Further investigation into the utility of anti-Xa levels for FXaI is warranted.

Comparison of Levothyroxine Dosing in Patients with and without Heart Failure.

Background: Evidence has shown that low thyroid hormone levels may lead to worse prognosis including a higher mortality rate in patients with heart failure (HF). Thyroid replacement increases cardiac output and exercise performance without causing significant adverse events. The purpose of this study is to compare levothyroxine doses in patients with and without HF.Methods: This single center, retrospective cohort study compared levothyroxine doses in ambulatory hypothyroid patients with a history of HF to those without a history of HF. Patients were stratified into three groups: no HF, HF with reduced ejection fraction (HFrEF, EF<40%), and other types of HF. The primary endpoint of average levothyroxine dose was analyzed using multivariable linear regression with variables determined a priori.Results: Three hundred patients were included in the study with 100 patients in each arm. Average levothyroxine doses (mcg/kg) were 1.5 ± 0.7, 1.6 ± 0.8, and 1.6 ± 0.9 for no HF, other types of HF, HFrEF, respectively (p= .61). Factors found to be significantly related to levothyroxine dosing included gender, drug-drug interactions, and the timing of clinic visit to lab draw. No differences were found in secondary outcomes including TSH levels, free T4, T3, and percentage of patients with elevated thyroid-stimulating hormone (TSH) among HFrEF, other types of HF, and no HF patients. Among HF patients, average ejection fractions were also similar comparing patients with elevated TSH, normal TSH, and low TSH.Conclusion: The dose of levothyroxine was not significantly different in HF patients compared to patients without HF.

Combined Insulin and GLP-1 Receptor Agonists: Simplifying Treatment or Adding Obstacles?

The US Food and Drug Administration recently approved 2 combination products containing a basal insulin and a glucagon-like peptide 1 receptor agonist: insulin glargine/lixisenatide and insulin degludec/liraglutide. These agents were shown to be noninferior in lowering hemoglobin A1c compared to basal insulin and are indicated for patients inadequately controlled on basal insulin or glucagon-like peptide 1 receptor agonists alone. The clinical implications of these agents are unclear due to limitations in the clinical trials and limited recommendations in current guidelines. While these agents may provide financial and adherence benefits, their role is likely limited to the outpatient setting. With the availability of these agents, concerns with transitions of care arise due to multiple vulnerabilities in reconciling these agents throughout the inpatient admission and discharge process. Provider awareness of the availability and dosing of insulin glargine/lixisenatide and insulin degludec/liraglutide is essential to reduce errors in the medication reconciliation process.

Time to Occurrence Based on Risk Stratification of Hospital-Acquired Venous Thromboembolism: A Retrospective Observational Cohort Study.

BACKGROUND: In-hospital venous thromboembolism (VTE) causes significant morbidity and mortality in hospitalized patients. The objective of our study is to determine the time to in-hospital VTE based on baseline risk stratification. METHODS: All adult patients admitted to a 900-bed academic tertiary referral hospital who developed a VTE during hospital admission from September 1, 2011, to June 30, 2015, were retrospectively analyzed. Patients were excluded if they were younger than 18 years or if the VTE was present on admission. RESULTS: The cohort included 400 patients, 224 (56%) males, median age 66 years. The median time to VTE was 8 days. Significant differences in time to VTE existed between the risk groups. CONCLUSION: Time to VTE in a broad hospitalized patient population differs based on admission risk group. This finding highlights the importance of performing risk assessment upon admission and subsequently with clinical changes to assess increases in risk scores.

Descriptive Analysis of Patient Readmissions Within 60 Days Due to Medication-Related Events.

BACKGROUND: Hospital readmissions have become a marker for quality health care. Readmissions secondary to failures of the medication use process are poorly documented and underrecognized. OBJECTIVE: To identify the incidence of readmissions related to the medication use process and identify associated patient- and therapy-related risk factors. METHODS: A prospective observational cohort study including patients discharged from an acute care medicine unit and readmitted within 60 days. The primary outcome was percentage of readmissions related to drug-related problems (DRPs) as defined by Pharmaceutical Care Network Europe (PCNE). Secondary outcomes included classification of problems using PCNE criteria, type and extent of pharmacist involvement in patient care, and identification of variables associated with a readmission related to a DRP. RESULTS: One hundred patients provided informed consent and were included for analysis. A DRP associated with readmission was identified in 64 patients. Sixty-one percent were classified as a potential problem with effect or lack of effect of pharmacotherapy. Patients who had a pharmacy consult were less likely to have a DRP (27% vs 47%; P = .04), and patients who missed follow-up appointments were more than 3 times as likely to have a DRP (20% vs 4%; P = .03). Presence of a pharmacy consult (odds ratio [OR], 0.38; 95% CI, 0.15-0.99; P = .05) and missed follow-up appointments (OR, 5.63; 95% CI, 1.52-20.86; P = .01) remained significant in a multivariate regression model. CONCLUSION: DRPs were frequent in patients who were readmitted within 60 days. Clinical pharmacist involvement in care and support for appropriate patient follow-up may reduce unnecessary admissions.

Patients with cirrhosis show a relative increase in thrombin generation that is correlated with lower antithrombin levels.

Predicting the risk of bleeding or thrombosis in cirrhotic patients is difficult due to reduced levels and dysregulation of both procoagulant and anticoagulant factors. We utilized thrombin generation and microvesicle analysis to better understand the regulation of haemostasis in cirrhotic patients. We studied 24 patients with cirrhosis vs. 21 healthy controls. Cirrhotic patients had reduced prothrombin activity (40 ±â€Š9 vs. 112 ±â€Š15), protein C activity (36 ±â€Š10 vs. 114 ±â€Š19) and antithrombin activity (43 ±â€Š14 vs. 109 ±â€Š10). Peak thrombin generation was reduced in cirrhotic patients (165 ±â€Š47 vs. 232 ±â€Š101), but the ratio of peak thrombin generation to prothrombin activity was increased in cirrhotic patients (4.2 ±â€Š1.0 vs. 2.1 ±â€Š0.9) indicating a relative increase in thrombin generation in cirrhosis. The termination time ratio was increased in cirrhotic patients (7.2 ±â€Š1.9 vs. 3.1 ±â€Š0.7) and correlated with reduced antithrombin levels, indicating that cirrhotic patients took longer to stop thrombin generation than controls. Cirrhotic patients showed reduced procoagulant microvesicles from platelets (39 500 ±â€Š24 800 vs. 107 700 ±â€Š74 200) and other cells, but levels overlapped with controls. Cirrhotic patients showed a wide range of procoagulant and anticoagulant levels leading to variability in the regulation of thrombin generation. In conclusion, compared with healthy controls, patients with cirrhosis have lower antithrombin levels that lead to slower downregulation of thrombin generation and more overall thrombin being produced for a given procoagulant level in blood, but also low normal levels of procoagulant microvesicles that would slow initiation of thrombin generation. Whether an individual cirrhosis patient is at a greater risk of bleeding vs. thrombosis may depend on their specific imbalance in procoagulants vs. anticoagulants.