Impact of treatment of hyperkalaemia on quality of life: design of a prospective observational cohort study of long-term management of hyperkalaemia in patients with chronic kidney disease or chronic heart failure in Japan.

Introduction: Hyperkalaemia (HK) is a frequent complication in patients with chronic kidney disease (CKD) and/or chronic heart failure (CHF). HK must be managed, both to protect patients from its direct clinical adverse outcomes and to enable treatment with disease-modifying therapies including renin-angiotensin-aldosterone system inhibitors. However, the experiences of patients undergoing treatment of HK are not clearly understood.

Treatment patterns and trajectories in patients after acute heart failure hospitalization.

Aims: The trajectories of systolic function after admission for acute heart failure (HF) and their effect on clinical outcomes have not been fully elucidated. We aimed to assess changes in left ventricular ejection fraction (LVEF) between the index and 1 year after discharge and to examine their prognostic implications.

Methods And Results: We extracted data from a prospective multicentre registry of patients hospitalized for acute HF and identified 1636 patients with LVEF data at admission and 1 year after discharge.

Impact of chronic potassium binder treatment on the clinical outcomes in patients with hyperkalemia: Results of a nationwide hospital-based cohort study.

Hyperkalemia (HK) is a common disorder in patients with heart failure or chronic kidney disease, and potassium binders (PBs) are recommended to control serum potassium (S-K) levels. Although HK is often a chronic condition, short-term and intermittent PBs treatment has been largely applied to control S-K levels, and little is known about the impact of long-term and chronic PBs treatment on clinical outcomes. This retrospective cohort study was conducted using a Japanese claims database (April 2008-September 2018).

Correction: Kohsaka et al. Risk-Benefit Balance of Renin-Angiotensin-Aldosterone Inhibitor Cessation in Heart Failure Patients with Hyperkalemia. 2022, , 5828.

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Association of Hyperkalemia and Hypokalemia with Patient Characteristics and Clinical Outcomes in Japanese Hemodialysis (HD) Patients.

This study aimed to examine the characteristics and clinical outcomes of Japanese hemodialysis patients with dyskalemia. A retrospective study was conducted using a large Japanese hospital group database. Outpatients undergoing thrice-a-week maintenance hemodialysis were stratified into hyperkalemia, hypokalemia, and normokalemia groups based on their pre-dialysis serum potassium (sK) levels during the three-month baseline period.

Clinical impact of suboptimal RAASi therapy following an episode of hyperkalemia.

Background: Hyperkalemia (HK) is a barrier to optimization of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy in heart failure (HF) and chronic kidney disease (CKD). We investigated cardiorenal risk associated with changes in RAASi regimen after an episode of HK in patients with HF and/or CKD.

Methods: This observational study utilized data from hospital records, claims, and health registers from the US (Optum's de-identified Market Clarity Data) and Japan (Medical Data Vision).

[Andexanet alfa (ONDEXXYA for Intravenous Injection 200 mg), a reversal agent for direct factor Xa inhibitors: pharmacological characteristics and clinical evidence].

Andexanet alfa is a modified recombinant human factor Xa (FXa) that was designed to serve as a binding target for FXa inhibitors as decoy protein. It sequesters FXa inhibitors from binding to endogenous FXa, thereby reversing anticoagulant effect of FXa inhibitors. Andexanet alfa has been approved in March 2022 in Japan for patients with life-threatening or uncontrolled bleeding while on treatment with a FXa inhibitor, apixaban, rivaroxaban, or edoxaban tosilate hydrate.

Machine learning models for prediction of HF and CKD development in early-stage type 2 diabetes patients.

Chronic kidney disease (CKD) and heart failure (HF) are the first and most frequent comorbidities associated with mortality risks in early-stage type 2 diabetes mellitus (T2DM). However, efficient screening and risk assessment strategies for identifying T2DM patients at high risk of developing CKD and/or HF (CKD/HF) remains to be established. This study aimed to generate a novel machine learning (ML) model to predict the risk of developing CKD/HF in early-stage T2DM patients.

Machine Learning Models Predicting Cardiovascular and Renal Outcomes and Mortality in Patients with Hyperkalemia.

Hyperkalemia is associated with increased risks of mortality and adverse clinical outcomes. The treatment of hyperkalemia often leads to the discontinuation or restriction of beneficial but potassium-increasing therapy such as renin-angiotensin-aldosterone inhibitors (RAASi) and high-potassium diet including fruits and vegetables. To date, limited evidence is available for personalized risk evaluation in this heterogeneous and multifactorial pathophysiological condition.

Risk-Benefit Balance of Renin-Angiotensin-Aldosterone Inhibitor Cessation in Heart Failure Patients with Hyperkalemia.

Background: Whether to continue renin−angiotensin−aldosterone system inhibitor (RAASi) therapy in patients with hyperkalemia remains a clinical challenge, particularly in patients with heart failure (HF), where RAASis remain the cornerstone of treatment. We investigated the incidence of dose reduction or the cessation of RAASis and evaluated the threshold of serum potassium at which cessation alters the risk−benefit balance. Methods: This retrospective analysis of a Japanese nationwide claims database investigated treatment patterns of RAASis over 12 months after the initial hyperkalemic episode.

Validation of a new instrument for measuring disease-specific quality of life: A pilot study among patients with chronic kidney disease and hyperkalemia.

Background: To prepare for a longitudinal study of the effects of potassium-lowering treatment on quality of life (QOL), we quantified the validity of a new disease-specific instrument for measuring QOL, using data from patients who had hyperkalemia (HK) due to chronic kidney disease (CKD) or chronic heart failure, and were also being treated with potassium binders (PBs).

Methods: In this cross-sectional study, the participants were 98 patients at five outpatient clinics in Japan. The outcome measures were the Medical Outcomes Study 36-item short-form (SF-36), a widely used generic measure of QOL, and the Quality of Life Disease-specific Impact Scale (QDIS-7), a recently-developed disease-specific measure of QOL.

Changes in Treatment Satisfaction Over 3 Years in Patients With Type 2 Diabetes After Initiating Second-line Treatment.

Context: J-DISCOVER is a prospective observational cohort study aiming to understand the current management of patients with early-stage type 2 diabetes mellitus (T2DM) in Japan, enrolling patients initiating second-line treatment.

Objective: The current analysis examined the change in treatment satisfaction during the study period and factors affecting this change among patients in J-DISCOVER.

Methods: We used data from the J-DISCOVER study, in which 1798 patients with T2DM aged ≥ 20 years were enrolled from 142 sites across Japan.

Cost-Effectiveness Analysis of Initiating Type 2 Diabetes Therapy with a Sodium-Glucose Cotransporter 2 Inhibitor Versus Conventional Therapy in Japan.

Introduction: Many patients with type 2 diabetes mellitus (T2DM) suffer from complications that impose substantial burdens on prognosis and medical costs. Accumulating evidence has demonstrated the clinical benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular and renal complications. However, the health economic impact of SGLT2i remains unclear.

Cost of healthcare utilization associated with incident cardiovascular and renal disease in individuals with type 2 diabetes: A multinational, observational study across 12 countries.

Aim: To examine how the development of cardiovascular and renal disease (CVRD) translates to hospital healthcare costs in individuals with type 2 diabetes (T2D) initially free from CVRD.

Methods: Data were obtained from the digital healthcare systems of 12 nations using a prespecified protocol. A fixed country-specific index date of 1 January was chosen to secure sufficient cohort disease history and maximal follow-up, varying between each nation from 2006 to 2017.

Health Care Cost Analysis of PPI or P-CAB-First Treatment in Patients With Gastroesophageal Reflux Disease.

Goals: The aim was to examine actual health care cost in patients with gastroesophageal reflux disease (GERD) who were initiated on proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) as first-line therapy in Japanese real-world clinical settings.

Background: To date, cost-utility evaluation of acid-suppressants treatment in Japan has only been conducted by model analysis.

Study: A cost utilization analysis was performed using a Japanese nationwide hospital-based claim database by extracting patients with GERD initiated on either PPI or P-CAB (242,102 pairs) and esomeprazole (EPZ) or P-CAB (241,825 pairs).

Manifestation of Heart Failure and Chronic Kidney Disease are Associated with Increased Mortality Risk in Early Stages of Type 2 Diabetes Mellitus: Analysis of a Japanese Real-World Hospital Claims Database.

Introduction: To assess the initial manifestation of comorbidities and their impact on mortality risk in patients with type 2 diabetes mellitus (T2DM) without a history of cardiovascular or renal complications (i.e., in the early stages of T2DM) compared with patients without T2DM.

Three-Year Glycaemic Control and Management in Patients with Type 2 Diabetes Initiating Second-Line Treatment in Japan: A Prospective Observational Study, J-DISCOVER.

Introduction: J-DISCOVER is a prospective, observational cohort study that aimed to understand characteristics, glycaemic control, comorbidities and real-world management of patients with early-stage type 2 diabetes mellitus (T2DM) in Japan, by enrolling patients initiating second-line treatment from both diabetes specialist and non-specialist care settings.

Methods: As part of the global DISCOVER programme, J-DISCOVER enrolled 1798 patients with T2DM aged at least 20 years old from 142 sites across Japan, from September 2014 to December 2015, and followed these patients for 3 years. Glycaemic control, body mass index (BMI), blood pressure, lipid profiles, treatment patterns, and prevalence of CKD and retinopathy were examined from baseline to 6, 12, 24 and 36 months, stratified by class of second-line treatment.

Cardiovascular and Renal Outcomes Associated With Hyperkalemia in Chronic Kidney Disease: A Hospital-Based Cohort Study.

Objective: To examine the association between hyperkalemia and long-term cardiovascular and renal outcomes in patients with chronic kidney disease.

Patients And Methods: An observational retrospective cohort study was performed using a Japanese hospital claims registry, Medical Data Vision (April 1, 2008, to September 30, 2018). Of 1,208,894 patients with at least 1 potassium measurement, 167,465 patients with chronic kidney disease were selected based on codes or estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.

Lower heart failure and chronic kidney disease risks associated with sodium-glucose cotransporter-2 inhibitor use in Japanese type 2 diabetes patients without established cardiovascular and renal diseases.

Aims: To examine heart failure (HF) and chronic kidney disease (CKD) risks reduction associated with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared to other glucose-lowering drugs (oGLD) in the early stage of type 2 diabetes patients without established cardiovascular or renal diseases (CVRD-free T2D).

Materials And Methods: We performed an observational cohort study using a Japanese hospital claims registry, Medical Data Vision. CVRD-free T2D patients were identified between 1 April 2014 and 30 September 2018.

Healthcare resource utilization after initiation of sodium-glucose co-transporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors or other glucose-lowering drugs in Japanese patients with type 2 diabetes.

Aim: To examine healthcare resource utilization in type 2 diabetes (T2D) patients after initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2is) versus dipeptidyl peptidase-4 inhibitors (DPP-4is) or other glucose-lowering drugs (oGLDs).

Materials And Methods: A cost-utilization analysis was performed using a nationwide hospital-based administrative claims database (Medical Data Vision) during 2014-2018 in Japan, where universal healthcare coverage is maintained under a single-payer system. Data on T2D patients initiated on either SGLT-2is or oGLDs during the study period (228 514 patients) were extracted and subjected to a 1:1 propensity score-matching analysis (7626 patient pairs for DPP-4is and 28 484 for oGLDs).

Current trends in diabetes mellitus database research in Japan.

With the widespread use of electronic medical records and administrative claims databases, analytic results from so-called real-world data have become increasingly important in healthcare decision-making. Diabetes mellitus is a heterogeneous condition that involves a broad spectrum of patients. Real-world database studies have been recognised as a powerful tool to understand the impact of current practices on clinical courses and outcomes, such as long-term glucose control, development of microvascular or macro-vascular diseases, and mortality.

Clinical and Economic Burden of Hyperkalemia: A Nationwide Hospital-Based Cohort Study in Japan.

Rationale & Objective: Hyperkalemia is a common electrolyte abnormality of chronic kidney disease and heart failure associated with increased mortality and morbidity. We aimed to assess the long-term economic burden of hyperkalemia.

Design: Observational cohort study using a Japanese nationwide hospital claims database (April 1, 2008, to September 30, 2018).

A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia.

Background: Hyperkalemia is associated with many chronic diseases and renin-angiotensin-aldosterone system inhibitor therapy. Sodium zirconium cyclosilicate (SZC), an oral, highly selective cation-exchanger, is approved for the treatment of hyperkalemia.

Methods: This phase 3, multicenter, open-label, single-arm, flexible-dose study assessed the safety and efficacy of SZC in Japanese patients with hyperkalemia during a correction phase of up to 3 days and long-term (1 year) maintenance phase (NCT03172702).

Lower cardiorenal risk with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes without cardiovascular and renal diseases: A large multinational observational study.

Aims: We compared the new use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus dipeptidyl peptidase-4 inhibitor (DPP4i) and the risk of cardiorenal disease, heart failure (HF) or chronic kidney disease (CKD), in patients with type 2 diabetes without a history of prevalent cardiovascular and renal disease, defined as cardiovascular and renal disease (CVRD) free, managed in routine clinical practice.

Materials And Methods: In this observational cohort study, patients were identified from electronic health records from England, Germany, Japan, Norway, South Korea and Sweden, during 2012-2018. In total, 1 006 577 CVRD-free new users of SGLT2i or DPP4i were propensity score matched 1:1.