Prevalence, clinical impact and costs of hyperkalaemia: Special focus on heart failure.

BACKGROUND: Hyperkalaemia is a potential life-threatening electrolyte abnormality. Although renin-angiotensin-aldosterone system inhibitors (RAASi) are potentially life-saving, they may contribute to hyperkalaemia. METHODS: The prevalence, comorbidities, comedications and 1-year outcomes of patients admitted or treated for hyperkalaemia were investigated in a large healthcare administrative database including 12 533 230 general population inhabitants. A similar analysis was performed in the Italian Network on Heart Failure (IN-HF), a cardiology registry of 1726 acute and 7589 chronic HF patients, stratified by serum potassium. General practice healthcare costs related to hyperkalaemia were also assessed. Hyperkalaemia was defined by hospital coding, potassium-binder prescription or serum levels (mild: 5-5.4, moderate-severe: ≥5.5 mmol/L). RESULTS: In the general population, the prevalence of hyperkalaemia was 0.035%. After excluding patients on haemodialysis, hyperkalaemia in the community (n = 2314) was significantly and directly associated with diabetes, chronic kidney disease, HF, RAASi prescriptions, 1-year hospitalisations and threefold annual healthcare costs, compared to age- and sex-matched non-hyperkalaemic subjects (n = 2314). In the IN-HF registry, hyperkalaemia affected 4.3% of acute and 3.6% of chronic patients and was significantly associated with diabetes, kidney disease and lesser use of RAASi, compared to normokalaemic patients. Among patients hospitalised for acute HF, those with hyperkalaemia at entry had significantly higher 1-year all-cause mortality compared with normokalaemic patients, even after adjustment for available confounders. CONCLUSIONS: Hyperkalaemia in the general population, although uncommon, was associated with increased hospitalisations and tripling of healthcare costs. Among HF patients, hyperkalaemia was common and associated with underuse of RAASi; in acutely decompensated patients, it remained independently associated with 1-year all-cause mortality.

The burden of hyperkalemia in Germany - a real world evidence study assessing the treatment and costs of hyperkalemia.

BACKGROUND: Hyperkalemia (HK) can affect health outcomes and quality of life, as it is referred to as a potentially life-threatening condition caused by an increased serum potassium concentration in the blood. Patients suffering from heart failure or chronic kidney diseases are at a higher risk of HK, which can further be amplified by the treatment received. To date, data on HK prevalence is lacking for Germany and the aims of this study were to assess HK and compare health-relevant outcomes and healthcare costs between HK patients and non-HK patients. METHODS: The InGef research database containing healthcare claims of over 4 million individuals in Germany was utilized for this retrospective, matched cohort analysis. Patients with non-acute outpatient treated and a subgroup of patients with chronic HK, were identified in 2015 with an individual 1 year pre- and post-index period, taking the first observable HK diagnosis/treatment in 2015 into account as the index event. To identify non-acute outpatient treated HK patients, at least two ICD-10-GM diagnosis codes E87.5 "Hyperkalemia" and/or prescriptions of polystyrene sulfonate were required. Chronic HK patients had additional diagnoses and/or prescriptions in all quarters following the first observable HK diagnosis. Patients without HK were matched 1:1 to the respective HK cohorts. RESULTS: In the year 2015, 3333 patients with non-acute outpatient treated HK were identified of which 1693 were patients with chronic HK. After matching, 3191 and 1664 HK patients and controls were available for analysis. A significantly higher number of hospitalizations was observed for both HK cohorts in comparison to their matched controls. Dialysis initiation as well as the healthcare costs were higher for both HK cohorts when compared to their matched counterparts. CONCLUSIONS: The disease burden was higher for patients with HK, based on a higher proportion of patients with dialysis initiation and higher healthcare costs.

Prevalence and economic burden of hyperkalemia in the United States Medicare population.

Objective: To estimate the prevalence and economic burden of hyperkalemia in the United States (US) Medicare population.Methods: Patients were selected from a 5% random sample of Medicare beneficiaries (01 January 2010-31 December 2014) to estimate the prevalence and economic burden of hyperkalemia. The prevalence for each calendar year was calculated as the number of patients with hyperkalemia divided by the total number of eligible patients per year. To estimate the economic burden of hyperkalemia, patients with hyperkalemia (cases) were matched 1:1 to patients without hyperkalemia (controls) on age group, chronic kidney disease [CKD] stage, dialysis treatment, and heart failure. The incremental 30-day and 1-year resource utilization and costs (2016 USD) associated with hyperkalemia were estimated.Results: The estimated prevalence of hyperkalemia was 2.6-2.7% in the overall population and 8.9-9.3% among patients with CKD and/or heart failure. Patients with hyperkalemia had higher 1-year rates of inpatient admissions (1.28 vs. 0.44), outpatient visits (30.48 vs. 23.88), emergency department visits (2.01 vs. 1.17), and skilled nursing facility admissions (0.36 vs. 0.11) than the matched controls (all p < .001). Patients with hyperkalemia incurred on average $7208 higher 30-day costs ($8894 vs. $1685) and $19,348 higher 1-year costs ($34,362 vs. $15,013) than controls (both p < .001). Among patients with CKD and/or heart failure, the 30-day and 1-year total cost differences between cohorts were $7726 ($9906 vs. $2180) and $21,577 ($41,416 vs. $19,839), respectively (both p < .001).Conclusions: Hyperkalemia had an estimated prevalence of 2.6-2.7% in the Medicare population and was associated with markedly high healthcare costs.

Cost-analysis of persistent hyperkalaemia in non-dialysis chronic kidney disease patients under nephrology care in Italy.

AIM: In patients with chronic kidney disease (CKD), hyperkalaemia (HK) (potassium level ≥ 5.0 mEq/L) is associated with poor clinical outcomes. This study provides novel insights by comparing management costs of CKD patients with normokalaemia vs those with persistent HK regularly followed in renal clinics in Italy. METHODS: To this aim, a Markov model over life-time horizon was developed. Time to end-stage renal disease (ESRD) and time to death in CKD patients were derived from an observational multi-centre database including 1665 patients with non-dialysis CKD stage 1-5 under nephrology care in Italy (15 years follow-up). Resource use for CKD and HK management was obtained from the observational database, KDIGO international guidelines, and clinical expert opinion. RESULTS: Results showed that patients with normokalaemia vs persistent HK brought an average per patient lifetime cost-saving of €16 059 besides delayed onset of ESRD by 2.29 years and increased survival by 1.79 years with increment in total survival and dialysis-free survival in normokalaemia that decreased from early to advanced disease. Cost-saving related to normokalaemia increased at more advanced CKD; however, it was already evident at early stage (3388.97€ at stage 1-3a). OWSA confirmed cost-saving associated with normokalaemia across all parameter variations. DISCUSSION AND CONCLUSION: This model is the first to simulate the impact of HK in non-dialysis CKD patients on economic and clinical outcomes using real-world data from nephrology clinics. In these patients, persistent HK results into higher lifetime costs, besides poorer clinical outcomes, that are evident since the early stages of CKD. Maintaining normokalaemia should therefore be of main concern in CKD treatment planning to improve long-term economic and clinical outcomes.

Healthcare resource utilisation and cost associated with elevated potassium levels: a Danish population-based cohort study.

OBJECTIVES: To investigate healthcare costs associated with hyperkalaemia (HK) among patients with chronic kidney disease (CKD), heart failure (HF) or diabetes. DESIGN: Before-after cohort study of patients with HK and matched patients without HK. SETTING: Population-based databases covering primary and secondary care for the entire of Northern Denmark. PARTICIPANTS: Patients with a first incident record of CKD (n=78 372), HF (n=14 233) or diabetes (n=37 479) during 2005-2011. Among all patients experiencing a first HK event (potassium level >5.0 mmol/L), healthcare costs were compared during 6 months before and 6 months after the HK event. The same cost assessment was conducted 6 months before and after a matched index date in a comparison cohort of patients without HK. PRIMARY AND SECONDARY OUTCOME MEASURES: Mean costs of hospital care, general practice and dispensed drugs converted to 2018 Euros. RESULTS: Overall, 17 747 (23%) CKD patients, 5141 (36%) HF patients and 4183 (11%) diabetes patients with a first HK event were identified. More than 40% of all HK patients across the patient groups had subsequent HK events with successively shorter times between the events. In CKD patients, overall mean costs were €5518 higher 6 months after versus before first HK, while €441 higher in matched CKD patients without HK, yielding HK-associated costs of €5077. Corresponding costs associated with a HK event were €6018 in HF patients, and €4862 in diabetes patients. CONCLUSIONS: Among CKD, HF and diabetes patients, an incident HK event was common, and a large proportion of the patients experienced recurrent HK events. Substantial increase in healthcare costs associated with a HK event was observed in the HK patients compared with non-HK patients. These results are important to better understand the potential economic impact of HK among high-risk comorbid patients in a real-wold setting and help inform decision-making for clinicians and healthcare providers.

The value of maintaining normokalaemia and enabling RAASi therapy in chronic kidney disease.

BACKGROUND: People with chronic kidney disease (CKD) are at an increased risk of developing hyperkalaemia due to their declining kidney function. In addition, these patients are often required to reduce or discontinue guideline-recommended renin-angiotensin-aldosterone system inhibitor (RAASi) therapy due to increased risk of hyperkalaemia. This original research developed a model to quantify the health and economic benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD. METHODS: A patient-level simulation model was designed to fully characterise the natural history of CKD over a lifetime horizon, and predict the associations between serum potassium levels, RAASi use and long-term outcomes based on published literature. The clinical and economic benefits of maintaining sustained potassium levels and therefore avoiding RAASi discontinuation in CKD patients were demonstrated using illustrative, sensitivity and scenario analyses. RESULTS: Internal and external validation exercises confirmed the predictive capability of the model. Sustained potassium management and ongoing RAASi therapy were associated with longer life expectancy (+ 2.36 years), delayed onset of end stage renal disease (+ 5.4 years), quality-adjusted life-year gains (+ 1.02 QALYs), cost savings (£3135) and associated net monetary benefit (£23,446 at £20,000 per QALY gained) compared to an absence of RAASi to prevent hyperkalaemia. CONCLUSION: This model represents a novel approach to predicting the long-term benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD, irrespective of the strategy used to achieve this target, which may support decision making in healthcare.

Cost-Effectiveness Analysis of Patiromer and Spironolactone Therapy in Heart Failure Patients with Hyperkalemia.

BACKGROUND AND OBJECTIVE: Certain patients with heart failure (HF) are unable to tolerate spironolactone therapy due to hyperkalemia. Patiromer is a novel agent used to treat hyperkalemia and has been shown to be efficacious, safe, and well-tolerated. The potential clinical outcomes and economic value of using patiromer and spironolactone in patients with HF unable to otherwise tolerate spironolactone due to hyperkalemia are unclear. The objective of this analysis was to model the potential pharmacoeconomic value of using patiromer and spironolactone in patients with a history of hyperkalemia that prevents them from utilizing spironolactone. METHODS: We performed a cost-effectiveness analysis of treatment with patiromer, spironolactone, and an angiotensin-converting enzyme inhibitor (ACEI) in patients with New York Heart Association (NYHA) class III-IV HF compared with ACEI alone. A Markov model was constructed to simulate a cohort of 65-year-old patients diagnosed with HF from the payer perspective across the lifetime horizon. Clinical inputs were derived from the RALES and OPAL-HK randomized trials of spironolactone and patiromer, respectively. Utility estimates and costs were derived from the literature and list prices. Outcomes assessed included hospitalization, life expectancy, and quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analyses were performed to test the robustness of the model findings. RESULTS: Treatment with patiromer-spironolactone-ACEI was projected to increase longevity compared with ACEI alone (5.29 vs. 4.62 life-years gained, respectively), greater QALYs (2.79 vs. 2.60), and costs (US$28,200 vs. US$18,200), giving an ICER of US$52,700 per QALY gained. The ICERs ranged from US$40,000 to US$85,800 per QALY gained in 1-way sensitivity analyses. CONCLUSION: Our results suggest that the use of spironolactone-patiromer-ACEI may provide clinical benefit and good economic value in patients with NYHA class III-IV HF unable to tolerate spironolactone due to hyperkalemia.

Development of a health economic model to evaluate the potential benefits of optimal serum potassium management in patients with heart failure.

AIMS: Patients with heart failure are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone system inhibitor (RAASi) agents. This study developed a model to quantify the potential health and economic value associated with sustained potassium management and optimal RAASi therapy in heart failure patients. MATERIALS AND METHODS: A patient-level, fixed-time increment stochastic simulation model was designed to characterize the progression of heart failure through New York Heart Association functional classes, and predict associations between serum potassium levels, RAASi use, and consequent long-term outcomes. Following internal and external validation exercises, model analyses sought to quantify the health and economic benefits of optimizing both serum potassium levels and RAASi therapy in heart failure patients. Analyses were conducted using a UK payer perspective, independent of costs and utilities related to pharmacological potassium management. RESULTS: Validation against multiple datasets demonstrated the predictive capability of the model. Compared to those who discontinued RAASi to manage serum potassium, patients with normokalemia and ongoing RAASi therapy benefited from longer life expectancy (+1.38 years), per-patient quality-adjusted life year gains (+0.53 QALYs), cost savings (£110), and associated net monetary benefit (£10,679 at £20,000 per QALY gained) over a lifetime horizon. The predicted value of sustained potassium management and ongoing RAASi treatment was largely driven by reduced mortality and hospitalization risks associated with optimal RAASi therapy. LIMITATIONS: Several modeling assumptions were made to account for a current paucity of published literature; however, ongoing refinement and validation of the model will ensure its continued accuracy as the clinical landscape of hyperkalemia evolves. CONCLUSIONS: Predictions generated by this novel modeling approach highlight the value of sustained potassium management to avoid hyperkalemia, enable RAASi therapy, and improve long-term health economic outcomes in patients with heart failure.

Expert Panel Recommendations for the Identification and Management of Hyperkalemia and Role of Patiromer in Patients with Chronic Kidney Disease and Heart Failure.

Virtual panel meetings were conducted among 7 physicians, all of whom are independent experts, including 3 nephrologists, 2 cardiologists, and 2 emergency medicine physicians (the panel). The panel met with the purpose of discussing the current treatment landscape, treatment challenges, economic impact, and gaps in care for patients with hyperkalemia that is associated with heart failure and chronic kidney disease. The stated goal of the panel discussion was to develop practical solutions in the identification and management of hyperkalemia in this patient population. The panel noted that hyperkalemia is a serious condition that can lead to life-threatening complications, yet the treatment paradigm for hyperkalemia has remained without major advances for approximately 50 years, until the approval of patiromer. A number of issues still exist in the management of this patient population, including the lack of uniform treatment guidelines and consensus regarding the approach to treatment. As part of its effort, the panel developed an algorithm, the Proposed Diagnostic Algorithm for Hyperkalemia Treatment in the Acute Care Setting/Chronic Care. The panel agreed that patiromer appears to be a viable option for the management of hyperkalemia in patients with chronic kidney disease and/or heart failure and in patients who experience chronic hyperkalemia. DISCLOSURES: This panel discussion was funded by Relypsa and facilitated by Magellan Rx Management. Rafique is a principal investigator for Relypsa and serves as a consultant for Instrumentation Laboratory, Magellan Health, Relypsa, and ZS-Pharma. Butler serves as consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CardioCell, Janssen, Merck, Novartis, Relypsa, and ZS-Pharma. Lopes and Farnum are employed by Magellan Rx Management. Rafique designed the management protocol for this panel discussion and contributed to the writing and editing of this report document. The other authors report no conflicting interests. Relypsa is the manufacturer of Veltassa (patiromer).

Clinical and Economic Impact of Hyperkalemia in Patients with Chronic Kidney Disease and Heart Failure.

BACKGROUND: Hyperkalemia (HK) is a concern for patients with chronic kidney disease (CKD) and heart failure (HF), and for those receiving treatments that inhibit the renin-angiotensin-aldosterone system (RAASi). An analysis of 1.7 million medical records of patients in the United States revealed that among individuals with more than 2 potassium values during 2007 to 2012, HK was detected in 34.6% of patients with CKD and 30.0% of patients with HF. OBJECTIVE: To evaluate the association of HK and use of RAASi therapies at optimal and suboptimal doses in patients with CKD and/or HF with health care resource utilization and overall cost of care in a diverse cohort of commercially insured patients. METHODS: This retrospective cohort study was conducted using medical and pharmacy claims from multiple regional health plans. Qualifying patients were ≥ 18 years old, continuously enrolled for 6 months before and throughout the study period (January 1, 2014, to December 31, 2015) and had an ICD-9-CM or ICD-10-CM diagnosis code of CKD and/or HF. Health care resource utilization, including hospital visits, length of stay, office visits, and associated medical and pharmacy costs, were assessed according to the 3 cohorts (CKD alone, HF alone, and concomitant CKD and HF). For the 3 cohorts, the results were also compared between patients with and without HK and between patients with and without RAASi use at optimal and suboptimal doses. Generalized linear models were used to further examine the predictors of medical and overall costs. RESULTS: In this study, 15,999 patients met inclusion criteria. Among patients using RAASi therapy, 26.8% received the optimal dose. Optimal dosing of RAASi was associated with decreased median outpatient office visits (8, 10, and 15, respectively, for patients with CKD, HF, and both CKD and HF) compared with suboptimal dosing of RAASi (12, 15, and 23, respectively). Similarly, optimal dosing of RAASi was associated with decreased overall median medical costs ($2,092, $4,144, and $7,762, respectively, for patients with CKD, HF, and both CKD and HF) compared with suboptimal dosing of RAASi ($3,121, $8,289, and $12,749, respectively). Patients with CKD, HF, or both CKD and HF, all in combination with HK, had higher overall costs, compared with those without HK. CONCLUSIONS: The results of this real-world analysis suggest that HK and suboptimal dosing of RAASI were associated with a median increase in outpatient office visits as well as increased overall medical costs among patients with CKD and/or HF. This evaluation of median costs suggests effective HK management may potentially reduce costs in patients with CKD and/or HF, including those currently receiving RAASi therapy. DISCLOSURES: This study was conducted by Magellan Rx Management and funded by Relypsa. Brenner, Alvarez, and Oestreicher were employed by Relypsa during the development of this study and the writing of this manuscript. Polson, Lord, Kangethe, Speicher, and Farnum are employees of Magellan Rx Management, which received funding from Relypsa for conducting the retrospective study and writing the manuscript. Study concept and design were contributed by Lord, Polson, Brenner, Alvarez, and Oestreicher. Data collection and interpretation were performed by Polson and Kangethe, with assistance from Lord. The manuscript was written by Farnum, with assistance from Kangethe and Speicher and revised by all authors.

A simple protocol to improve safety and reduce cost in hemodialysis patients undergoing elective surgery.

BACKGROUND: When patients with end-stage renal disease (ESRD) miss their routine intermittent hemodialysis (IHD), electrolyte abnormalities and volume overload often occur. An institutional protocol to ensure that patients receiving IHD have elective surgeries scheduled within 24 hours after their dialysis may reduce procedural delays or cancellations caused by hyperkalemia and hypervolemia after a missed IHD session. The effect of this protocol was evaluated. METHODS: A retrospective chart review was performed for ESRD patients receiving IHD who underwent surgery from 6 months before to 6 months after the institutional protocol was implemented. Preoperative potassium values, timing of IHD relative to surgery, and the nature of surgery (elective or emergent) were documented. The percentage of patients having IHD more than 24 hours before their elective surgery was compared before and after protocol implementation. Average potassium values were compared when IHD occurred within 24 hours vs. more than 24 hours, using t test analysis. Cost associated with delay and cancellation for IHD was also explored. RESULTS: Of the 15,799 cases performed, 190 involved ESRD patients receiving IHD. Before the protocol, 32.1% of elective cases (n = 17) involved patients scheduled for surgery more than 24 hours after IHD vs. 12.0% (n = 6) after the protocol. Preoperative potassium values were less when patients underwent IHD within 24 hours than at more than 24 hours (mean [SD], 4.32 [0.6] mEq/L vs 4.63 [0.8] mEq/L; P = .03). CONCLUSIONS: The simple scheduling policy is effective at reducing both cost and unnecessary perioperative risks for patients.