Which factors reduce potassium excretion and increase risk of hyperkalemia?

• A. diabetes, use of RAASi, use of beta-blockers
• B. CKD, diabetes, use of loop diuretics
• C. CKD, diabetes, use of RAASi
• D. higher age, CKD, use of loop diuretics

The correct answer is C.

Hello, my name is Kevin Damman. I'm a heart failure cardiologist in the University Medical Center in Groningen in the Netherlands. And today I will be talking about the population of patients with heart failure and chronic kidney disease that may benefit from potassium binding.

As an introduction you know that heart failure and chronic kidney disease are intertwined entities. That means they have influence on each other. When one organ deteriorates this might lead to deterioration of the other. And we have been very successful in treating both entities. With RAASi therapy, as you can see on this slide. So with ACEis, ARBs, MRAs, ARNI and perhaps SGLT2 as well, we see now that we can improve outcome in these patients leading to improved mortality, less harshly rehospitalization and important, a better quality of life.

When you start a patient on RAASi therapy, it is important to realize that just starting is not enough. You need to get some effort into it. And this means that this takes time, perseverance sometimes, to uptitrate these patients to the highest tolerable dose. Even if the patient needs to temporarily discontinue the treatment, because of perceived adverse events, it is important to reinitiate and restart the patient on the therapy.

And the reason this is so important is depicted on the right side, where you can see in a patient with heart failure from the biostats cohort, that if a patient was on the highest tolerable dose of RAASi therapy the prognosis of deviations was best.

So what are the perceived reasons for not uptitrating these therapies in heart failure? And these are just listing ACEis, ARBs and MRAs. And as you can see these are three main categories. One is worsening renal function,so bumping creatinine.The other could be associated with hyperkalemia. And another important factor is hypotension, so blood pressure drop. And of course these factors have influence on each other. In the frail age patient population, when you start an ACEi or ARB, this might result in hypotension, related renal disfunction and that may result in hyperkalemia.

We're going to focus on hyperkalemia and how this may influence the therapy in the future. As you can see from this slide, when we talk about hyperkalemia this is mostly regarded as a potassium above five. Important to realize that even in the outpatient setting, changes in potassium may happen fast. Of course we know this from acute heart failure, if your patient is admitted. We also have therapies that influence potassium levels and also in the inpatient clinic changes in potassium are relevant, but also can be very quick.

What you also need to realize is that to be in normokalemia is most important because on each side of the spectrum there is an increase in risk. As well with hypokalemia, as with hyperkalemia. And in different patient population as you can see here.

So how often do we see hyperkalemia in patients with chronic heart failure? So this slide shows you the incidence of hyperkalemia across heart failure trials, across RAASi trials. What you can see that around five to six percent of patients develop hyperkalemia. But what strongly bumps out are those trials with MRA. So spironolactone and eplerenone where the risk of incident hyperkalemia is strongly increased.

Interestingly, in this slide you can see the effect of ARNI in HFrEF and HFpEF, where you can see that the incidence of hyperkalemia was actually lower in the active arm.

So how does the potassium level influence the effect of guideline recommended therapies? So here you can see that across the entire spectrum of potassium levels, spironolactone was able to decrease the risk of mortality compared with placebo in the RALES study.So the baseline potassium had no effect on the effect of spironolactone.

What you can see here is that when you have RAASi therapy and no hyperkalemia, this means that the survival of this patient is best. While if there is hyperkalemia and the patient does not tolerate RAASi therapy those are the patients who have the worst outcome.

How do we manage these patients in real life? It shows you here, about 40 percent have either down-titration or discontinuation of their guideline recommended therapy based on their potassium level. This means this has impact for their outcome on long-term.

Which are the patients that are at risk for developing hyperkalemia? This is a slide showing you a multitude of factors that are associated with hyperkalemia. Of course we know that aging population, diabetes, potassium-sparing diuretics have an effect. But one of the most important factors here is of course chronic kidney disease.Which is on the right side of the graph, where you see a strong increased risk of hyperkalemia.

And this is further acknowledged by the finding from biostat again. That is the aging population with chronic kidney disease, also therapy which we start like RAASi, MRAs and also disease severity. So more advanced heart failure patients have a higher risk of developing hyperkalemia.

So summarizing: who may benefit in the future from potassium binding? Well, hyperkalemia is associated with a frail population, those with lower eGFR, with more comorbidities and more severe disease. And of course, with the introduction of RAASi we see more hyperkalemia. Together with worsening renal function, hyperkalemia promotes the risk of stopping or temporarily halting guideline recommended therapies.Which means that patients are not uptitrated and their risk of mortality is higher.

Finally, managing hyperkalemia is important because it gives the caregiver more confidence in the safety of these patients and if a patient is longer on guideline recommended therapy this might in the end improve their long-term survival.

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