ZORA real-world evidence demonstrates that Lokelma substantially increases cardiorenal patients’ chances of maintaining lifesaving RAASi therapy in hyperkalaemia patients – AstraZeneca

Results from the real-world ZORA observational multi-country study presented at the American Society of Nephrology (ASN) 2023 shows that treating hyperkalaemia (HK) with the potassium binder Lokelma (sodium zirconium cyclosilicate) can allow patients with chronic kidney disease (CKD) or heart failure (HF) to maintain their lifesaving renin-angiotensin-aldosterone system inhibitor (RAASi) therapy . Analysis showed that patients treated with Lokelma were substantially more likely to maintain guideline-recommended RAASi therapy at 6 months following a hyperkalaemia (HK) episode, compared to patients who were not treated with a potassium binder, the odds were ~2.5-times higher (OR 2.56; 95% CI: 1.92–3.41; P<0.0001).

Additional analysis also showed that the risk of progression to end-stage kidney disease (ESKD), diagnosed as chronic kidney disease (CKD) stage 5 or the initiation of dialysis, within 6 months following a hyperkalaemia episode was 73% higher in patients who discontinued RAASi treatment, and 60% higher in patients who down-titrated vs maintained RAASi therapy. This builds on previous data showing that HK-related RAASi reduction increases the risk of cardiorenal events and mortality among patients with CKD or HF.

Anjay Rastogi, M.D., Ph.D., Clinical Chief of Nephrology, UCLA Health, said: “Evolving science shows that proactive management of hyperkalaemia with a potassium binder allows guideline recommended RAASi therapy to be maintained at the optimised dose levels to improve outcomes for patients with CKD or heart failure. Yet, real-world evidence provides a sharp reality check of what’s actually happening to cardiorenal patients following an episode of hyperkalaemia in clinical practice and the serious consequences down-titration and discontinuation of RAASi therapy can have, leading to poorer outcomes and increased mortality.”

Ruud Dobber, Executive Vice-President, BioPharmaceuticals Business Unit, AstraZeneca, said: “These data add to the body of evidence that if hyperkalaemia is not effectively managed, it can lead to worsening cardiovascular and kidney disease outcomes and increased mortality due to down-titration or discontinuation of RAASi. Lokelma can be a pivotal therapeutic strategy to address this urgent disease burden. At AstraZeneca, we remain committed to working with the cardiorenal community to enable guideline recommended RAASi therapy and achieve more effective cardiorenal protection for patients.”

This RWE study indicates an urgent need for improved guideline adherence in managing HK to enable patients to stay on their lifesaving RAASi therapy.

ZORA study : The ZORA study is a global RWE programme, which is examining the current management of HK and its’ clinical consequences. The ZORA study ‘Maintained RAASi Therapy with Sodium Zirconium Cyclosilicate Following a Hyperkalaemia Episode’ used health registers and hospital medical records to identify patients with CKD and/or HF eceiving RAASi therapy who experienced a HK episode. The SZC cohort included 565 (US), 776 (Japan), and 56 (Spain) patients treated with SZC for at least 120 days; the No K+ binder cohort included 2068 (US), 2629 (Japan), and 203 (Spain) patients without a K+ binder prescription. Propensity score (PS) matching was applied to balance the SZC cohort to the No K+ binder cohort on baseline characteristics. The second ZORA study on ‘Association Between Reduced RAASi Therapy and Progression to ESKD in Hyperkalaemic CKD Patients’ included 11,873 (US) and 1427 (Japan) patients with CKD Stage 3/4 and baseline RAASi use who experienced an HK episode.2 Based on RAASi prescriptions 3 months before versus after the HK episode, patients were categorised as down titrated, discontinued, or maintained RAASi treatment.