OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure

Inclusion Criteria:

Recruiting will take place mainly from specialist care at University hospitals or Province hospitals in Sweden. But some of patients might have simultaneous follow-up at primary care as well.

Each subject should meet all of the inclusion criteria and none of the exclusion criteria for this study. Under no circumstances can there be exceptions to this rule.

Inclusion criteria

For inclusion in the study subjects should fulfil the following criteria:

1. Obtain signed informed consent prior to any study specific procedures

2. >18 yrs.

3. LVEF ≤ 40% within past 2 years (including recovered EF later on).

4. NYHA II-IV.

5. On optimal treatment including ACE/ARB/ARNI, beta blockers, SGLT2 inhibitor, as perphysician´s judgement.

6. Suboptimal treatment with MRA (defined as: no use or ≤ 25 mg daily)

7. And one of following:

8. Prior hyperkalemia (S-K> 5.0 mmol/L or P-K> 4.8 mmol/L*) during MRA treat-mentwithin last 24 months, and current S-K ≤ 5.0 or P-K ≤ 4.8 mmol/L

9. Current S-K 4.5-5.0 mmol/L or P-K 4.3-4.8 mmol/L, and potential risk ofhyper-kalemia as indicated by eGFR 30-45 ml/min/1,73 m2 (modified MDRD formula)

10. Current S-K 5.1-5.9 mmol/L or P-K 4.9-5.7 mmol/L

• Corresponding plasma K (P-K) level is 0.2 mmol lower than serum K(S-K) (The Nordic Reference Interval Project).

Depending on the S-K status during screening, patients are divided into two groups before treatment initiation /run-in:

• Group 1: Patients who are hyperkalemic (S-K 5.1 - 5.5 mmol/L measured within last 2weeks)

• Group 2: Patients who are normokalemic (S-K 3.5 - 5.0 mmol/L) during screening butare at a high risk of developing hyperkalemia associated with MRA initiation /increase. Namely, one (or both) of the following:

• Prescription of MRA within last 12 months and documented hyperkalemia after MRAprescription

• S-K 4.5-5.0 mmol/L and GFR < 45 mL/min/1,73 m2

Note: All S-K related limits in this protocol concern serum measurements. In Sweden it is plasma that is analyzed, which makes 4.8 mmol/l (plasma) equivalent to 5.0 mmol/L(serum)

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are ful-filled:

1. Symptomatic hypotension (< 90/60 mmHg)

2. eGFR < 30 ml/min/1,73 m2 (modified MDRD formula)

3. HF due to restrictive cardiomyopathy, hypertrophic (obstructive) cardio-myopathy orprimary valvular disease

4. Current/recent (within 3 months) hospitalization due to myocardial infarc-tion,unstable angina pectoris, coronary revascularization (percutaneous coronaryintervention or coronary artery bypass grafting), or other interven-tions (valvularrepair/replacement, cardiac transplantation or implantation of a ventricularassistance device)

5. Ongoing or planned dialysis

6. Prior history of hypersensitivity (other than hyperkalemia) to a MRA, or SZC

7. Advanced malignancy requiring treatment

8. History of QT prolongation associated with other medications that requireddiscontinuation of that medication.

9. Congenital long QT syndrome.

10. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymp-tomaticsustained ventricular tachycardia. Subjects with atrial fibrillation controlled bymedication are permitted

11. QTc(f) > 550 msec

12. Currently pregnant (confirmed with positive pregnancy test) or planned pregnancy orbreast-feeding

13. Can not sign informed consent.