Hi, everyone. I'm Aaron Wong from the United Kingdom. It's my pleasure to share with you some of our practical experience and model for optimizing RAASi-based therapy. These are my speaker's disclosures.

For patient with heart failure, CKD, and type 2 diabetes, RAASi therapy is a first-line recommendation from multiple international guidelines based on multiple trials showing benefits on mortality and morbidity. RAASi therapy is the cornerstone treatment for patient with heart failure, diabetes, and chronic kidney disease. Submaximal dosing and discontinuation of RAASi therapy has been associated with a doubling risk of mortality in this group of patients. Some physician may think that putting someone on RAASi therapy may be enough, but this study just showed that the dosing are equally important.

If we know that this therapy are lifesaving, then why are we not putting this patient on these medications? These are some of the common reasons: advanced age, perceived frailty, or lack of infrastructure to monitor and to optimize the patients. Some of these factors are somewhat more addressable, such as hyperkalemia. Hyperkalemia can be frightening because it has been shown to cause fatal arrhythmias, and it affects the physician confidence and comfort when prescribing RAASi therapy. As you can see here, following an episode of hyperkalemia, almost half of these patients have a reduction in RAASi therapy or discontinuation of RAASi therapy.

Though hyperkalemia can potentially be manageable, there are now two novel potassium binders that we can use to control hyperkalemia to allow continuation of RAASi therapy, such as patiromer and sodium zirconium cyclosilicate. It is important to know that once these binders were stopped at the end of the clinical trials, there was a rebound hyperkalemia indicating that hyperkalemia is a persistent risk in this group of patients. The ESC expert consensus give us a recommendation a few years ago, suggesting that this binder should be considered to use to allow optimization of RAASi therapy.

How can we translate this clinical trial evidence and guidelines recommendation into clinical practice? I'm now going to share with you, our real world use of a potassium binder, sodium zirconium cyclosilicate to optimize RAASi therapy in patient with heart failure with reduced ejection fraction. This is a retrospective analysis of a data of 44 patients followed over 25 months. The mean age of our cohort is 75 years. With fairly advanced cardiac and renal dysfunction, LV ejection fraction is 29% and 86% of this patient in NYHA class II to III. 75% of this patient have CKD Stage 3b or 4, with significant comorbidities. One-third of this patient already have a hospitalization for heart failure in a preceding 24 months. NT-proBNP is elevated at just under 3500 nanogram per liter, with a mean serum potassium of 5.7 millimoles per liter. Only one-third of these patients were on guidelines recommended quadruple therapy prior to starting on the binders. With the use of a potassium binder, we observe an increased uptake in dosing of a guidelines recommended therapy. 100% of an ARNi were achieved in patient with the binders. We also double the percentage of patient being prescribed a MRA from 52% to 89% with an increased mean dose of 13 milligram to 31 milligram daily. We also doubled the number of patients on the guidelines recommended quadruple therapy from 32% to 64% Potassium binder, sodium zirconium cyclosilicate, were very effective to control high potassium levels while we optimize RAASi therapy throughout the study period.

With the increased uptake of this guideline recommended therapy for heart failure, we also observe an improvement in heart failure markers and clinical outcomes. Left ventricular ejection fraction increased from 29% to 36%. We observe a reduction of NT-proBNP from just under 3500 to just over 2000. There were no significant difference in kidney function and blood pressure. We also observed a reduction in hospitalization for decompensated heart failure. The survival rate was 91% throughout the study period, considered these patients have fairly advanced cardiac and renal dysfunction. These potassium binders were very well tolerated throughout the study period.

What are the factors we should consider before we start somebody on the potassium binders to allow long-term RAASi therapy? We should review the etiology for heart failure, kidney disease, and also hyperkalemia. We should look into the patient medications and encourage the patient to adhere to a low-potassium diet. We should carry out a thorough clinical assessment for our patient and determine the types of heart failure. There are some of the practical issues we should consider, such as medication adherence and compliance with monitoring.

We drafted a local protocol to empower our healthcare professionals to initiate and maintain patients on potassium binders and RAASi therapy. We give recommendation of the frequency of the monitoring based on the potassium levels and the clinical status of the patient. We also give recommendation on when and how to adjust the potassium binders and also the RAASi therapy. We also incorporated national guidelines into our protocol, trying to help our healthcare professional not just to adapt to changes in potassium levels but also to adapt changes of therapy based on changes on renal function. Let's not forget about the importance of encouraging our patient to adhere on a low-potassium diet. There are medications that can also increase potassium levels, we need to be aware of. We also need to be aware of potential drug interaction with these potassium binders.

The recently published Delphi consensus highlighted that hyperkalemia is a predictable, treatable, and manageable condition. Hyperkalemia is perceived as a barrier of optimizing RAASi therapy, and the downtitration of RAASi should be discouraged and only carried out as a last resort. This consensus also highlighted that novel potassium binders should be the preferred agent to allow optimization of RAASi therapy. This document also emphasized the importance of cross-specialty collaboration and support between cardiology, renal department, and also other healthcare professionals.

In conclusion, RAASi therapy is a cornerstone treatment for patients with heart failure and kidney disease. These guidelines recommended evidence-based medication can improve outcome and the dosing is important. Hyperkalemia often perceived as a barrier to optimize RAASi therapy. Our data have shown that a selective use of potassium binders can allow optimization of RAASi therapy in patients with heart failure with reduced ejection fraction. Our data also show that these potassium binders are well tolerated and very effective to maintain potassium level to allow continuation of RAASi therapy. The better uptake of this medication has been shown to be associated with a reduction in NT-proBNP, and potential renal and cardiac outcome. The applicability of this real world experience of using potassium binders to optimize RAASi therapy will be further expanded upon with the outcomes of the randomized controlled trials REALIZE-K.

Thank you for listening.

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