ABSTRACT
BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns. OBJECTIVES: The purpose of this study was to assess whether sodium zirconium cyclosilicate (SZC), a nonabsorbed crystal that traps and rapidly lowers potassium, enables MRA use in patients with HFrEF and prevalent hyperkalemia (or at high risk). METHODS: REALIZE-K is a prospective, double-blind, placebo-controlled trial in patients with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal therapy (except MRA), and prevalent hyperkalemia (or at high risk). During the open-label run-in, all participants underwent protocol-mandated spironolactone titration (target: 50 mg daily); those with prevalent (cohort 1) or incident (cohort 2) hyperkalemia during titration started SZC. Participants achieving normokalemia while on spironolactone ≥25 mg daily were randomized to continuing SZC or matching placebo for 6 months. The primary composite endpoint was proportion of participants with optimal response (normokalemia, on spironolactone ≥25 mg daily, no rescue for hyperkalemia [months 1-6]). RESULTS: Of 365 patients (run-in), 202 were randomized. Baseline characteristics included mean age 70 years, prevalent comorbidities (78% estimated glomerular filtration rate <60 mL/min/1.73 m2, 38% atrial fibrillation/flutter), high N-terminal pro B-type natriuretic peptide (median 1,136 pg/mL), and high HFrEF therapy use (64% sacubitril/valsartan, 96% beta-blocker, 42% sodium glucose co-transporter 2 inhibitor). At randomization, 78% were receiving spironolactone 50 mg daily. CONCLUSIONS: REALIZE-K is the first trial to evaluate whether SZC can enable rapid and safe MRA optimization and long-term continuation in patients with HFrEF and prevalent/high risk of hyperkalemia. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients with Symptomatic HFrEF Receiving Spironolactone; NCT04676646).
ABSTRACT
OBJECTIVES: To describe chronic kidney disease (CKD) regarding treatment rates, comorbidities, usage of CKD International Classification of Diseases (ICD) diagnosis, mortality, hospitalisation, evaluate healthcare utilisation and screening for CKD in relation to new nationwide CKD guidelines. DESIGN: Population-based observational study. SETTING: Healthcare registry data of patients in Southwest Sweden. PARTICIPANTS: A total cohort of 65 959 individuals aged >18 years of which 20 488 met the criteria for CKD (cohort 1) and 45 470 at risk of CKD (cohort 2). PRIMARY AND SECONDARY OUTCOME MEASURES: Data were analysed with regards to prevalence, screening rates of blood pressure, glucose, estimated glomerular filtration rate (eGFR), Urinary-albumin-creatinine ratio (UACR) and usage of ICD-codes for CKD. Mortality and hospitalisation were analysed with logistic regression models. RESULTS: Of the CKD cohort, 18% had CKD ICD-diagnosis and were followed annually for blood pressure (79%), glucose testing (76%), eGFR (65%), UACR (24%). UACR follow-up was two times as common in hypertensive and cardiovascular versus diabetes patients with CKD with a similar pattern in those at risk of CKD. Statin and renin-angiotensin-aldosterone inhibitor appeared in 34% and 43%, respectively. Mortality OR at CKD stage 5 was 1.23 (CI 0.68 to 0.87), diabetes 1.20 (CI 1.04 to 1.38), hypertension 1.63 (CI 1.42 to 1.88), atherosclerotic cardiovascular disease (ASCVD) 1.84 (CI 1.62 to 2.09) associated with highest mortality risk. Hospitalisation OR in CKD stage 5 was 1.96 (CI 1.40 to 2.76), diabetes 1.15 (CI 1.06 to 1.25), hypertension 1.23 (CI 1.13 to 1.33) and ASCVD 1.52 (CI 1.41 to 1.64). CONCLUSIONS: The gap between patients with CKD by definition versus those diagnosed as such was large. Compared with recommendations patients with CKD have suboptimal follow-up and treatment with renin-angiotensin-aldosterone system inhibitor and statins. Hypertension, diabetes and ASCVD were associated with increased mortality and hospitalisation. Improved screening and diagnosis of CKD, identification and management of risk factors and kidney protective treatment could affect clinical and economic outcomes.
