Hyperkalemia in heart failure: Why should we care?

Hello everyone. It is a pleasure for me being here. Thank you for the invitation. My name is Clara Bonanad. I am a cardiologist from Valencia, Spain. And a professor of the University of Valencia. I'm going to speak about hyperkalemia in heart failure. Why should we care?

These are my disclosures.

As we know, there are many subgroups of patients with a higher incidence of hyperkalemia. For example, patients with advanced stages of CKD, also patients with diabetes mellitus, also patients with resistant hypertension and in advanced age. Moreover, it is to know that in patients with chronic heart failure, the frequency of hyperkalemia could be up to 30 to 50% of our patients. Above all in advanced stage of the disease or in patients with a background therapy of ACE inhibitors. Furthermore, there is a therapeutic dilemma in managing hyperkalemia, while we try to optimize RAASi therapy. Guidelines tell us that we have to use, We should use these four foundational therapies to reduce mortality for all patients. And guidelines recommend us to use RAASi, because RAASi improves outcomes, RAASi reduces cardiovascular morbidity and mortality and also slows CKD progression. But RAASi could produce hyperkalemia and that leads to RAASi dose reduction or discontinuation that worsens our patient's prognosis.

In this slide we can see, in an observational registry, that heart failure and RAASi therapy were observed as a major risk factor for developing hyperkalemia, along with other comorbidities as chronic kidney disease. And there is an unmet need in our cardiology population. Above all, patients with heart failure with reduced ejection fraction, because persistent hyperkalemia in our patients with acute heart failure in this study was associated with higher risk of cardiovascular death, heart failure related death and sudden cardiac death compared to those who achieve or maintain normokalemia.

Moreover, patients with heart failure who have had an episode of hyperkalemia are at higher risk of developing recurrent episodes. 40% of our patients could have a recurrent episode. With successively shorter time between episodes that could impact the prognosis of our patient. And this has an impact on our treatment and adherence to guidelines, because guidelines, European guidelines and American guidelines, tell us that we should use ACE inhibitors. To the doses tested in clinical trials or to the maximally tolerated dose for the patient. But renal impairment and hyperkalemia are the major causes for not using RAASi and MRA.

So in this unmet necessity, we can think about potassium binders. Moreover, in the recent published American guidelines for the first time recommend the use of potassium binder, patiromer and sodium zirconium cyclosilicate, for the management of hyperkalemia. With a recommendation of class IIb to enable us to use RAASi therapy, because there are more benefits than risks. And also, for the first time, these guidelines do not recommend or mention the use of a diuretic or low potassium diet with low intake of fruits and vegetables to manage hyperkalemia.

And it has been demonstrated in several studies that hyperkalemia is a frequent cause of underuse of RAASi therapy and MRA in heart failure with reduced ejection fraction patients. And moreover, in our real world practice, the discontinuation of RAASi therapy persists following a hyperkalemia event. Almost 76% of patients were not reintroduced to MRA therapy during the subsequent year. And the mean duration of the RAASi discontinuation in heart failure,could be until two years.

In this international register with more than 6,000 patients with hyperkalemia, We can see that it is very important to adhere to guidelines, because to reach at least 50% of the objective dose recommended in guidelines, is associated with better prognosis. And not to reach at least 50% of the recommended dose is associated with heart failure death. And moreover, down-titration or discontinuation of RAASi therapy in this study was associated with doubling of mortality across patients subtypes among patients with heart failure.

What is the reason to justify the need to optimize treatments in heart failure? Despite the risk of hyperkalemia? The reasons to optimize is because RAASi or ARNI, Beta-blockers, MRA, SGLT2 inhibitor. The effect of these four medications reduce the mortality by 73% in two years,compared with only beta blocker and RAASi and prolongs survival for six years. Moreover the degree of benefit of each class of these four foundational drugs is independent of each other. So its initiation with low doses and progressive increase are effective in reducing morbidity and mortality in our heart failure patients with reduced ejection fraction. However we have to deal, we should deal with the risk of hyperkalemia in certain situations I mentioned before.

And in recent years, several expert consensus of heart failure in hyperkalemia patients with cardiovascular disease, treated with RAASi and MRA. It tells us that patiromer and sodium zirconium cyclosilicate can be considered in our heart failure patients with or without CKD to control hyperkalemia in selected patients, and to allow us to initiate or uptitrate MRA and other RAASi. And also, they highlight that if we have a patient with a potassium above 5 mmol/L and that patient is not on an optimal dose of RAASi therapy, We should think about the new potassium binders.

To conclude, hyperkalemia is common in heart failure. And in other subgroup of patients, as well as patients with CKD, RAASi therapy, patients with diabetes mellitus, resistant hypertension and older age. Hyperkalemia is clearly associated with a worse prognosis and limits the use of a specific drug for heart failure, with reduced ejection fraction. New pharmacological strategies could help us to optimize treatments in heart failure. And maybe the most important thing is to be aware today, awareness. And the early detection of hyperkalemia or risk of developing it, that could improve not only the prognosis of our heart failure patient, but also the treatment of our patients.

Thank you very much for your attention.