Assessing patiromer utilization and associated serum potassium changes in US veterans with prior sodium polystyrene sulfonate exposure.

Untreated chronic hyperkalemia is associated with an increased risk of mortality. Novel potassium binders (e.g., patiromer) are new additions to the clinician's armamentarium. Prior to their approval, clinicians often considered trialing sodium polystyrene sulfonate. The study objective was to assess patiromer utilization and associated changes in serum potassium (K+) in US veterans with prior sodium polystyrene sulfonate exposure. This was a real-world observational study of US veterans with chronic kidney disease and a baseline K+ ≥ 5.1 mEq/L, initiated on patiromer between January 1, 2016, and February 28, 2021. The primary endpoints were patiromer utilization (dispensations and treatment courses), and K+ change at 30-, 91-, and 182-day follow-up (FU) intervals. Patiromer utilization was described using Kaplan-Meier probabilities and the proportion of days covered. Descriptive changes in population average K+ were obtained from a pre-post design using single-arm within-patient pre-post lab pairs and paired t tests. Two hundred five veterans met the study criteria. We observed an average of 1.25 (95% CI, 1.19-1.31) treatment courses and a median treatment duration of 64 days. Fifty veterans (24.4%) had >1 course, and 17.6% of patients remained on their initial patiromer treatment course until the end of the 180-day FU. The mean K+ value was 5.73 mEq/L (5.66-5.79) at baseline, 4.95 mEq/L (95% CI, 4.86-5.05) at the 30-day interval, 4.93 mEq/L (95% CI, 4.84-5.03) at the 91-day interval, and 4.9 mEq/L (95% CI, 4.8-4.99) at the 182-day interval. Novel potassium binders (e.g., patiromer) are newer chronic hyperkalemia management tools for clinicians. The average population K+ decreased to <5.1 mEq/L at all follow-up intervals. Patiromer appeared to be well tolerated with nearly 18% of patients remaining on their initial treatment course during the entire 180-day FU period. The median treatment duration was 64 days and approximately 24% of patients initiated a second course during FU.

Real-world evaluation of patiromer utilization and its effects on serum potassium in veterans with end stage kidney disease.

Hyperkalemia (serum potassium [K+] ≥5.1) is life-threatening in patients diagnosed with end stage kidney disease (ESKD). Patiromer is approved for the treatment of hyperkalemia, although its role in hyperkalemic patients with ESKD is not well understood. This study describes real-world patiromer utilization in an ESKD population and its corresponding association with serum K+ level changes. The study population was comprised of US veterans with an outpatient dispensing of patiromer and 2 or more International Classification of Diseases diagnostic codes for ESKD. A treatment course of patiromer was defined by serial dispensing events without a 30-day gap. Patiromer utilization was described by duration, average dose, persistence, and proportion of days covered during patiromer course. Mean serum K+ values were described for baseline and 3 follow-up intervals during the 180-day follow-up period. There were 458 patients with ESKD included in the study. On average, patients had 1.24 (95% CI: 1.20-1.29) patiromer courses. Half of the population discontinued their first patiromer course within 30 days, while approximately 10% of patients remained persistent at the end of the 180-day period and 102 (22.3%) patients started a second course during the 180-day follow up period. Average serum K+ concentrations during baseline and the 3 evaluation intervals during the 180-day follow-up were 5.91 mEq/L (5.85-5.97), 4.94 mEq/L (4.86-5.03), 4.89 mEq/L (4.8-4.98) and 4.88 mEq/L (4.8-4.96). Few patients remained persistent on their initial course of patiromer at the end of follow-up, but approximately 20% of patients initiated a second treatment episode after a 30-day gap in treatment during the 180-day follow-up period. Nonetheless, average serum K+ in ESKD patients were sustainably reduced by approximately 1 mEq/L during follow-up.

Multiple comorbid conditions and healthcare resource utilization among adult patients with hyperkalemia: A retrospective observational cohort study using association rule mining.

Objectives: To estimate the prevalence of specific comorbid conditions (CCs) and multiple comorbid conditions (MCCs) among adult patients with hyperkalemia and examine the associations between MCCs and healthcare resource utilization (HRU) and costs. Methods: This retrospective observational cohort study was conducted using a large administrative claims database. We identified patients with hyperkalemia (ICD-10-CM: E87.5; or serum potassium >5.0 mEq/L; or NDC codes for either patiromer or sodium polystyrene sulfonate) during the study period (1/1/2016-6/30/2019). The earliest service/claim date with evidence of hyperkalemia was identified as index date. Qualified patients had ≥12 months of enrolment before and after index date, ≥18 years of age. Comorbid conditions were assessed using all data within 12 months prior to the index date. Healthcare resource utilization and costs were estimated using all data within 12 months after the index date. Association rule mining was applied to identify MCCs. Generalized linear models were used to examine the associations between MCCs and HRU and costs. Results: Of 22,154 patients with hyperkalemia, 94% had ≥3 CCs. The most common individual CCs were chronic kidney disease (CKD, 85%), hypertension (HTN, 83%), hyperlipidemia (HLD, 81%), and diabetes mellitus (DM, 47%). The most common dyad combination of CCs was CKD+HTN (71%). The most common triad combination was CKD+HTN+HLD (62%). The most common quartet combination was CKD+HTN+HLD+DM (36%). The increased number of CCs were significantly associated with increased ED visits, length of hospital stays, and total healthcare costs (all p-value < 0.0001). Conclusions: MCCs are very prevalent among patients with hyperkalemia and are strongly associated with HRU and costs.

Healthcare utilization and expenditures associated with hyperkalemia management: a retrospective study of Medicare Advantage patients.

AIMS: This study aimed to estimate the association of patiromer exposure vs. no potassium (K+) binder (NoKb) exposure with healthcare utilization and expenditures among a cohort of Medicare Advantage patients with hyperkalemia (HK). METHODS: Using Optum's Clinformatics Data Mart (study period 2016-2019), the authors assessed propensity score-matched patients (1:1) with a serum K+ concentration ≥5.0 mmol/L and an HK diagnosis that were exposed to patiromer or NoKb on baseline characteristics. The following outcomes were compared: (1) inpatient/emergency department (ED) encounters, (2) inpatient costs greater than or equal to mean Medicare Advantage inpatient cost (i.e. $14,900), and (3) the relative healthcare spending rate. Logistic regression and zero-inflated negative binomial regression were used to analyze the outcomes. RESULTS: The study cohort included 1,539 patiromer and NoKb matched pairs. Baseline characteristics were (patiromer/NoKb): age 74/75 years; female 42/40%; serum K+ 5.6/5.6 mmol/L; eGFR rate 36/36 mL/min/1.73 m2; low-income subsidy 42/41%, chronic kidney disease 96/96%; end-stage renal disease 12/12%; and congestive heart failure 37/36%. A total of 253 matched pairs (506 patients) remained uncensored and were analyzed at 6 months. Inpatient/ED encounters were observed for 25% (patiromer) and 37% (NoKb) (odds ratio [OR] 0.58, 95% confidence interval [CI]: 0.38-0.89). The relative odds of having inpatient costs ≥$14,900 were ∼50% less for patients exposed to patiromer vs. NoKb (OR [95% CI]: 0.47 [0.25-0.89]). The relative total healthcare spending rate (including inpatient, outpatient, ED, and pharmacy costs) was 19% less for patients exposed to patiromer vs. NoKb (spending rate ratio [95% CI]: 0.81 [0.67-0.98]). CONCLUSION AND LIMITATIONS: Among Medicare Advantage patients with HK, patiromer exposure (vs. NoKb) was associated with statistically significant reductions in the proportion with inpatient/ED encounters, inpatient costs ≥$14,900, and lower total healthcare spending. Further research, with larger sample size, is warranted to fully validate these findings.

Hyperkalemia Management in Older Adults With Diabetic Kidney Disease Receiving Renin-Angiotensin-Aldosterone System Inhibitors: A Post Hoc Analysis of the AMETHYST-DN Clinical Trial.

RATIONALE & OBJECTIVE: Older people are more likely to have reduced kidney function and multiple comorbid conditions predisposing them to hyperkalemia. This post hoc subgroup analysis aimed to evaluate the effectiveness of patiromer, a sodium-free nonabsorbed polymer, in lowering serum potassium levels in older patients receiving a renin-angiotensin-aldosterone system inhibitor with chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and hypertension. STUDY DESIGN: Post hoc subgroup analysis of the randomized open-label AMETHYST-DN clinical trial. SETTING & PARTICIPANTS: Multicenter clinical trial. Individuals 75 years and older with CKD, T2DM, hypertension, and hyperkalemia at baseline (N = 60; mean age, 77 years; 30 men [50%]; mean estimated glomerular filtration rate, 41.6 ± 14.3 mL/min/1.73 m2). INTERVENTION: Patients with hyperkalemia were randomly assigned to receive patiromer at doses ranging from 4.2 to 16.8 g twice daily. OUTCOMES: We evaluated changesin serum potassium levels from baseline to week 4 and time points through 52 weeks. Long-term safety and tolerability were assessed through the end of 52 weeks and included frequency of adverse events, clinical laboratory measurements, and vital signs. RESULTS: Of 306 AMETHYST-DN participants, 60 were 75 years or older. All 60 patients had CKD and T2DM; 37% had heart failure. At screening, patients had an estimated glomerular filtration rate of 42 mL/min/1.73 m2, median urinary albumin-creatinine ratio of 127 mg/g, and baseline mean serum potassium level of 5.19 mEq/L. Mean serum potassium level was reduced at each time point from the first postbaseline visit (day 3) through week 52. LIMITATIONS: This small subgroup analysis was not prespecified and therefore randomization was lost; thus, it should be considered hypothesis generating. CONCLUSIONS: Among older patients with hyperkalemia and diabetic kidney disease, treatment with patiromer resulted in significant reductions in serum potassium levels after 4 weeks and lasted through 52 weeks. Patiromer was effective in lowering serum potassium levels and was well tolerated in older patients. FUNDING: Vifor Pharma, Inc. TRIAL REGISTRATION: NCT01371747.

A Predictive Model for Progression of Chronic Kidney Disease to Kidney Failure Using a Large Administrative Claims Database.

BACKGROUND: To create an appropriate chronic kidney disease (CKD) management program, we developed a predictive model to identify patients in a large administrative claims database with CKD stages 3 or 4 who were at high risk for progression to kidney failure. METHODS: The predictive model was developed and validated utilizing a subset of patients with CKD stages 3 or 4 derived from a large Aetna claims database. The study spanned 36 months, comprised of a 12-month (2015) baseline period and a 24-month (2016-2017) prediction period. All patients were ≥18 years of age and continuously enrolled for 36 months. Multivariate logistic regression was used to develop models. Prediction model performance measures included area under the receiver operating characteristic curve (AUROC), calibration, and gain and lift charts. RESULTS: Of the 74,114 patients identified as having CKD stages 3 or 4 during the baseline period, 2476 (3.3%) had incident kidney failure during the prediction period. The predictive model included the effect of numerous variables, including age, gender, CKD stage, hypertension (HTN), diabetes mellitus (DM), congestive heart failure, peripheral vascular disease, anemia, hyperkalemia (HK), prospective episode risk group score, and poor adherence to renin-angiotensin-aldosterone system inhibitors. The strongest predictors of progression to kidney failure were CKD stage (4 vs 3), HTN, DM, and HK. The ROC and calibration analyses in the validation sample demonstrated good predictive accuracy (AUROC=0.844) and calibration. The top two prediction deciles identified 70.8% of patients who progressed to kidney failure during the prediction period. CONCLUSION: This novel predictive model had good accuracy for identifying, from a large national database, patients with CKD who were at high risk of progressing to kidney failure within 2 years. Early identification using this model could potentially lead to improved health outcomes and reduced healthcare expenditures in this at-risk population.

A Model to Predict Risk of Hyperkalemia in Patients with Chronic Kidney Disease Using a Large Administrative Claims Database.

BACKGROUND: Chronic kidney disease (CKD) is responsible for substantial clinical and economic burden. Drugs that inhibit the renin-angiotensin-aldosterone system inhibitors (RAASi) slow CKD progression in many common clinical scenarios. Guideline-directed medical therapy requires maximal recommended doses of RAASi, which clinicians are often reluctant to prescribe because of the associated risk of hyperkalemia (HK). OBJECTIVE: This study aims to develop and validate a model to identify individuals with CKD at elevated risk for developing HK over a 12-month period on the basis of lab, medical, and pharmacy claims. METHODS: Using claims from a large US healthcare payer, we developed a model to predict the probability of individuals identified with CKD but not HK in 2016 (baseline year [BY]) who developed HK in 2017 (prediction year [PY]). The study population was comprised of members continuously enrolled with medical and pharmacy benefits and CKD (BY). Members were excluded from the analysis if they had HK (by lab results or diagnosis code) or dialysis (BY). Prediction model performance measures included area under the receiver operating characteristic curve (AUROC), calibration, and gain and lift charts. RESULTS: Of 435,512 members identified with CKD but not HK (BY), 6235 (1.43%) showed incident HK (PY). Compared with individuals without incident HK (PY), these members had a higher comorbidity burden, use of RAASi, and healthcare utilization. The AUROC and calibration analyses showed good predictive accuracy (area under the curve [AUC]=0.843 and calibration). The top 2 HK-prediction deciles identified 75.94% of members who went on to develop HK (PY). CONCLUSION: Guideline-recommended doses of RAASi therapy can be limited by the risk of HK. Novel potassium binders may permit more patients at risk to benefit from these maximal RAASi doses. This predictive model successfully identified the risk of developing HK up to 1 year in advance.

Real-world management of hyperkalemia with patiromer among United States Veterans.

Objective: Patiromer is a sodium-free, non-absorbed, potassium (K+) binder approved for the treatment of hyperkalemia (HK). Among US Veterans with HK, this retrospective, observational cohort study evaluated patiromer utilization, RAASi continuation, and K+ concentration change following patiromer initiation.Methods: Using data from the Veterans Affairs Corporate Data Warehouse, Veterans with HK (K+ ≥5.1 mmol/L) were included upon patiromer initiation (index date) during the study period (1/2016-8/2018). All patients had heart failure (HF), diabetes, or chronic kidney disease (CKD). Patients with end-stage renal disease were excluded. The following outcomes were assessed within 6-months post-patiromer initiation: patiromer utilization (using proportion of days covered); K+ concentration change (pre- vs post-initiation); and RAASi continuation.Results: 288 Veterans with HK were included. Baseline characteristics were: median age 70 years, African-American race 24%, diabetes 83%, HF 32%, CKD 95%, and median K+ concentration 5.7 mmol/L. At 1, 3, and 6 months post-index, the median patiromer PDC was 100%, 66%, and 44%, respectively. K+ concentration reductions post-patiromer initiation were, on average, - 1.0 mmol/L (P < 0.001). At 3-6 months, 71% of patiromer initiators had K+ <5.1 mmol/L and 95% had K+ <5.5 mmol/L. RAASi therapy was continued in >80%-90% of patiromer-treated patients.Conclusions: The real-world utilization results suggest patiromer is used for the chronic management of HK. Clinically relevant K+ concentration reductions were observed at all study time points. The successful management of HK may have contributed to the observed high rate of RAASi therapy continuation. Further research is warranted to corroborate and extend these findings.

The Economic Implications of Hyperkalemia in a Medicaid Managed Care Population.

BACKGROUND: Hyperkalemia, defined as a serum potassium level >5 mEq/L that results from multiple mechanisms, is a serious medical condition that can lead to life-threatening arrhythmias and sudden cardiac death. The coexistence of cardiac and renal diseases (ie, cardiorenal syndrome) significantly increases the complexity of care, but its economic impact is not well-characterized in this understudied Medicaid managed care population with hyperkalemia. OBJECTIVE: To calculate the economic impact of hyperkalemia on patients with cardiorenal syndrome in a Medicaid managed care population in the United States using real-world data. METHODS: In this retrospective cohort study, we used a proprietary Medicaid managed care database from 1 southern state. The total study population included 3563 patients, including 973 patients with hyperkalemia and 2590 controls (without hyperkalemia), who were matched based on age, comorbidities, and Medicaid eligibility status and duration, during a 30-month period between 2013 and 2016. The inclusion criteria for the hyperkalemia cohort were age ≥18 years, Medicaid-only insurance status, coded cardiorenal diagnosis, and a claim for hyperkalemia during the study period. The cost was determined using paid claims data. RESULTS: The mean healthcare costs (medical and pharmacy per member per year [PMPY] for patients with hyperkalemia was higher than that for the control cohort without hyperkalemia ($56,002 vs $23,653, respectively). These cost differences were driven by medical costs accrued in the hyperkalemia and in the control cohorts ($49,648 and $18,399 PMPY, respectively). Two of the largest drivers of the medical cost variance were inpatient costs ($33,116 vs $10,629 PMPY for the hyperkalemia and control cohorts, respectively) and dialysis costs ($2716 vs $810 PMPY, respectively). The medical loss ratios were 552% for the hyperkalemia cohort and 260% for the control cohort. Both cohorts had revenue deficits to the health plan, but the hyperkalemia cohort had double the medical loss ratio compared with the control cohort. CONCLUSIONS: The findings from this Medicaid managed care population suggest that hyperkalemia increases healthcare utilization and costs, which were primarily driven by the costs associated with inpatient care and dialysis. Our findings demonstrate that the Medicaid beneficiaries who have cardiorenal comorbidities accrue high costs to the Medicaid health plan, and these costs are even higher if a hyperkalemia diagnosis is present. The very high medical loss ratio for the hyperkalemia cohort in our analysis indicates that enhanced monitoring and management of patients with hyperkalemia should be considered.

Effect of Patiromer on Hyperkalemia Recurrence in Older Chronic Kidney Disease Patients Taking RAAS Inhibitors.

BACKGROUND: Older people are predisposed to hyperkalemia because of impaired renal function, comorbid conditions, and polypharmacy. Renin-angiotensin-aldosterone system inhibitors (RAASi), which are recommended to treat chronic kidney disease and heart failure augment the risk. Patiromer, a nonabsorbed potassium binder, was shown in the phase 3 OPAL-HK study to decrease serum potassium in patients with chronic kidney disease taking RAASi. We studied the efficacy and safety of patiromer in a prespecified subgroup of patients aged ≥65 years from OPAL-HK. METHODS: Chronic kidney disease patients with mild or moderate-to-severe hyperkalemia received patiromer, initially 8.4 g/d or 16.8 g/d, respectively, for 4 weeks (treatment phase, part A). Eligible patients entered an 8-week randomized withdrawal phase (part B) and continued patiromer or switched to placebo. RESULTS: Mean ± standard error change in serum potassium from baseline to week 4 of part A (primary endpoint) in patients aged ≥65 years was -1.01 ± 0.05 mEq/L (P < .001); 97% achieved serum potassium 3.8-<5.1 mEq/L. The serum potassium increase during the first 4 weeks of part B was greater in patients taking placebo than in those taking patiromer (P < .001). Fewer patients taking patiromer (30%) than placebo (92%) developed recurrent hyperkalemia (serum potassium ≥5.1 mEq/L). Mild-to-moderate constipation occurred in 15% (part A) and 7% (part B) of patients aged ≥65 years. Serum potassium <3.5 mEq/L and serum magnesium <1.4 mg/dL were infrequent (4% each in patients aged ≥65 years in part A). CONCLUSIONS: Patiromer reduced recurrent hyperkalemia and was well tolerated in older chronic kidney disease patients taking RAASi.

Managing hyperkalemia in high-risk patients in long-term care.

Hyperkalemia is common among elderly patients and is associated with an increase in morbidity and mortality. Patients at highest risk for developing hyperkalemia are those with chronic kidney disease (CKD) and heart failure (HF), particularly those on guideline-recommended inhibitors of the renin-angiotensin-aldosterone system (RAAS). Hyperkalemia remains a challenge for clinicians practicing in the long-term care setting as they are often faced with the difficult decision of down-titrating or discontinuing RAAS inhibitors in response to hyperkalemia in the very patients who derive the greatest benefit from these agents. In the past, options to chronically manage hyperkalemia were limited. Patiromer was approved for the treatment of hyperkalemia in 2015 and has been shown to maintain normokalemia for up to 52 weeks in patients with CKD and/or HF on RAAS inhibitors. With the emergence of a new hyperkalemia treatment, there could be a paradigm shift away from the discontinuation of guideline recommended therapies, allowing the continuation of RAAS inhibitor therapy to effectively manage HF symptoms and reduce the risk of rehospitalization in patients with HF, and slow the progression to end-stage renal disease in patients with CKD.

A multi-institutional medical educational collaborative: advocacy training in California pediatric residency programs.

Educational collaboratives offer a promising approach to disseminate educational resources and provide faculty development to advance residents' training, especially in areas of novel curricular content; however, their impact has not been clearly described. Advocacy training is a recently mandated requirement of the Accreditation Council for Graduate Medical Education that many programs struggle to meet.The authors describe the formation (in 2007) and impact (from 2008 to 2010) of 13 California pediatric residency programs working in an educational collaboration ("the Collaborative") to improve advocacy training. The Collaborative defined an overarching mission, assessed the needs of the programs, and mapped their strengths. The infrastructure required to build the collaboration among programs included a social networking site, frequent conference calls, and face-to-face semiannual meetings. An evaluation of the Collaborative's activities showed that programs demonstrated increased uptake of curricular components and an increase in advocacy activities. The themes extracted from semistructured interviews of lead faculty at each program revealed that the Collaborative (1) reduced faculty isolation, increased motivation, and strengthened faculty academic development, (2) enhanced identification of curricular areas of weakness and provided curricular development from new resources, (3) helped to address barriers of limited resident time and program resources, and (4) sustained the Collaborative's impact even after formal funding of the program had ceased through curricular enhancement, the need for further resources, and a shared desire to expand the collaborative network.

Implementation of clinical practice guidelines for pediatric weight management.

OBJECTIVE: To evaluate the effect of computer-assisted decision tools that standardize pediatric weight management in a large, integrated health care system for the diagnosis and management of child and adolescent obesity. STUDY DESIGN: This was a large scale implementation study to document the impact of the Kaiser Permanente Southern California Pediatric Weight Management Initiative. An average of 739, 816 outpatient visits per year in children and adolescents from 2007 to 2010 were analyzed. Height, weight, evidence of exercise and nutrition counseling, and diagnoses of overweight and obesity were extracted from electronic medical records. RESULTS: Before the initiative, 66% of all children and adolescents had height and weight measured. This increased to 94% in 2010 after 3 years of the initiative (P < .001). In children and adolescents who were overweight or obese, diagnosis of overweight or obesity increased significantly from 12% in 2007 to 61% in 2010 (P < .001), and documented counseling rates for exercise and nutrition increased significantly from 1% in 2007 to 50% in 2010 (P < .001). CONCLUSIONS: Computer-assisted decision tools to standardize pediatric weight management with concurrent education of pediatricians can substantially improve the identification, diagnosis, and counseling for overweight or obese children and adolescents.