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.

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.

Background Hyperkalemia is a serious metabolic condition and can lead to life-threatening cardiac arrhythmias and sudden death. Guideline-directed medications that affect the renin-angiotensin-aldosterone axis can increase serum potassium and may limit their use. Hyperkalemia has been shown to drive healthcare resource utilization (HRU) and costs for patients with cardiorenal conditions. Objectives To describe hyperkalemic patient characteristics and quantify patient HRU and costs relative to normokalemic patients from a large US health plan. Methods A retrospective cohort study that identified and evaluated a hyperkalemic patient population from a large administrative claims database. The observation period was 1 January 2015 to 31 May 2018, with a 1-year follow-up period after the index date (the earliest service/claim with evidence of hyperkalemia). Primary patient outcomes included inpatient admissions, emergency department (ED) visits, primary care physician (PCP)/specialist visits, length of stay (LOS) and associated medical and pharmacy costs. This hyperkalemic cohort was stratified by renin-angiotensin-aldosterone system inhibitor (RAASi) utilization and chronic kidney disease (CKD) stage for the economic analysis. Key findings 86,129 adult patients with hyperkalemia were evaluated in the study cohort (median age: 69 years). There were more males [45,155 (52%)], with the majority of patients located in the Southern United States [45,541 (51%)] and a 70/30 split of Medicare to a commercial health plan. Most patients had CKD, hypertension and hyperlipidemia; ≥80% of the patients had ≥4 comorbidities. Over 40% of patients were not receiving RAASi therapy, and potassium binder use was low (&lt;5%). Patients using optimal-dose RAASi with proportion of days covered ≥80% were observed to have the lowest HRU for inpatient admissions, ED and PCP visits and LOS days. Conclusions Hyperkalemia is associated with substantial HRU and costs. The development of a quality improvement program structured around the management of hyperkalemia in individuals with heart failure, diabetes and/or CKD may be necessary.

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.

Renin-angiotensin-aldosterone system inhibitor (RAASi) therapy has been shown to improve outcomes among patients with congestive heart failure, diabetes, or renal dysfunction. These patients are also at risk for the development of hyperkalemia (HK), often leading to down-titration and/or discontinuation of RAASi therapy. Patiromer is the first sodium-free, non-absorbed potassium (K +) binder approved for the treatment of hyperkalemia (HK) in over 50 years. We described the association between use of K + binders (Patiromer and sodium polystyrene sulfonate [SPS]) and renin-angiotensin-aldosterone system inhibitor (RAASi), on healthcare resource utilization (HRU). The study population consisted of Medicare Advantage patients with HK (K + � 5.0 mmol/L) in Optum's Clinformatics ® Data Mart between 1/1/2016-12/31/2017. Patiromer and (SPS) initiators, and HK patients not exposed to a K + binder (NoKb) were included. The index date was the date of the first K + binder dispensing or HK diagnosis. Outcomes assessed at 6 months post-index were: (1) K + binder utilization, (2) RAASi continuation, and (3) HRU (pre-vs post-index). HRU change was analyzed using McNemar's statistical test. Study cohorts included 610 (patiromer), 5556 (SPS), and 21,282 (NoKb) patients. Overall baseline patient characteristics were: mean age 75 years; female 49%, low-income subsidy 29%, chronic kidney disease 48% (63% for patiromer cohort), and congestive heart failure 29%. At 6 months post-index, 28% (patiromer) and 2% (SPS) remained continuously exposed to the index K + binder. RAASi continued for 78% (patiromer), 57% (SPS), and 57% (NoKb). The difference (pre-vs postindex) in hospitalized patients was:-9.4% (patiromer; P<0.05),-7.2% (SPS), and +16.8% (NoKb; P<0.001). Disparate K + binder utilization patterns were observed. The majority of patiromer patients continued RAASi therapy while the percentage of SPS patients that continued RAASi therapy was lower, overlapping CIs were observed. Following continuous