The prevalence of RAASi uptitration limiting hyperkalemia and the suitability of potassium binders among patients suffering from heart failure with reduced ejection fraction
Authors: Muk B , Vamos M , Vagany D , Majoros Z.S , Pilecky D , Juhasz I.Z.S , Szogi E , Kosa K , Borsanyi T , Dekany M , Kiss R.G , Nyolczas N 
Published: November 2020

Abstract

Background
The use of the renin-angiotensin-aldosteron-system inhibitor (RAASi) regime is crucial to reduce the mortality and morbidity of heart failure with reduced ejection fraction (HFrEF). However, it is well known that among real life circumstances it is challenging to reach the guideline-recommended target doses (TDs) of RAASi-s, due to the occurrence of side effects (e.g. hyperkalemia). Based on the ESC expert consensus document, it is recommended to reduce the RAASi dosages or discontinue the therapy when significant hyperkalemia (HK) occurs (serum potassium &gt;5.0 mmol/l or &gt;6.0 mmol/l, respectively). Within the last years, trials of patiromer and zirconium cyclosilicate demonstrated dose-dependent effect of these drugs enhancing potassium level lowering. The ongoing DIAMOND study examining the effect of patiromer among patients with previous HK (se potassium &gt;5mmol/l) in the effect of RAASi-s in HFrEF hopefully will answer the question whether the use of a potassium binder and in its effect the use of TD-s of RAASi translates to significant mortality benefit in HFrEF.

Aim
To assess the prevalence of RAASi uptitration limiting HK and to assess the potential suitability of potassium binders among HFrEF patients followed-up regularly at a heart failure outpatient clinic (HFOC).

Methods
Data of 557 consecutive HFrEF patients (NYHA: 3.1±0.8; LVEF: 27.4±6.6%; age: 61.2±13.0 years; male: 76.3%; ischemic: 47.2%; atrial fibrillation: 27.3%; diabetes: 35.7%; hypertension: 72.7%, systolic blood pressure: 124.3±24.3mmHg, eGFR: 65.6±23.6 ml/min/1.73m2) was analyzed. At baseline ACEi/ARBs in 33.6%, BBs in 40.9%, MRAs in 37.9% of the total cohort (TC) were used.

Results
After therapy optimization (TO) ACEis/ARBs were applied in 97.5% and TD (equivalent to at least 10 mg of enalapril b.i.d.) was reached in 59.4% of the TC. BBs in 90.7%, TDs of BBs in 48.3%, MRAs in 64.3%, TDs of MRAs in 24.6% of the TC were applied. In 100 patients (17.9%) the TDs of ACEi/ARBs and MRAs were reached simultaneously. Among those 457 patients not reaching the TD of ACEi/ARBs and/or the TD of MRAs the occurrence of HK (se potassium &gt;5 mmol/l) was quite frequent (45.3%, 207 patients), the prevalence of HK with the need of permanent dose reduction of RAASi regime (se potassium&gt;5.5 mmol/l) was 10.5% (48 patients) and the prevalence of HK resulting permanent discontinuation of RAASi (se potassium &gt;6.0 mmol/l) was 2.8% (13 patient) during the TO.

Conclusions
The current ESC guidelines recommend the use of TDs or maximal tolerated doses of RAASi-s in HFrEF. In a real-world patient cohort when every effort was made to reach the TDs, the TD of ACEi/ARBs and the TD of MRAs was reachable only in 17.9% of patients due the side effects observed during the TO. The occurrence of HK preventing to reach the TD, resulting down-titration or temporary/permanent discontinuation of RAASi-s and representing potential suitability for potassium binders is significant among optimally treated HFrEF patients.

Funding Acknowledgement
Type of funding source: None