Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) constitutes of four medications that substantially reduce morbidity and mortality, and improve quality of life. In routine clinical practice, various physician- and patient-related factors lead to suboptimal initiation and uptitration of GDMT to optimal dosing, which is associated with worse patient outcomes. A perceived major barrier to the optimalization of GDMT are changes in kidney function and electrolytes, which prompts physicians to halt uptitration, reduce doses, or even discontinue GDMT. Changes in kidney function and electrolytes during optimalization of GDMT are common, but not associated with adverse events.

The hypothesis of this study is that a reduction in the number of kidney function assessments during initiation and uptitration of GDMT in HFrEF patients will lead to higher achieved doses of GDMT without safety concerns.

Objective: To assess the effect of a reduction in kidney function assessments during optimalization of GDMT in patients with HFrEF on the achieved GDMT doses, safety, and clinical outcomes.

Study design: Randomized, controlled open-label study

Study population: 344 patients with new-onset or sub-optimally treated HFrEF referred to the outpatient clinic for optimalization of GDMT

Intervention (if applicable): Randomization to limited number of kidney function assessments or standard of care

Primary endpoint: The achieved average percentage dose of reno-active GDMT at 6 months relative to optimal dose.

Secondary endpoints: The achieved percentage dose of the individual reno-active GDMT drug classes at 6 months relative to optimal dose, and time to first occurrence of unplanned heart failure visit, heart failure hospitalization, or all-cause mortality till 9 months.

Safety endpoints: Incidence of doubling of creatinine, estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m2, potassium >6 mmol/L, or potassium <3.5 mmol/L at any timepoint. An additional composite kidney endpoint is defined as a combination of hospitalization for kidney failure, dialysis or end-stage kidney disease (eGFR <15 mL/min/1.73 m2).

Inclusion Criteria:

1. Able and willing to give written informed consent
2. Age ≥ 18 years
3. Diagnosed with HFrEF (LVEF≤ 45%) according to criteria from 2021 European Society of Cardiology guidelines for heart failure
4. Less than 100% target dose of 2 individual reno-active GDMT classes (ACEi/ARB/ARNI, MRA or SGLT-2i)

Exclusion Criteria:

1. eGFR<25 mL/min/1.73 m2 measured up to 30 days before the first visit
2. Potassium > 5.5 mmol/L or <3.5 mmol/L at screening
3. Known intolerance or allergy to two individual GDMT
4. Signs of hemodynamic instability and/or cardiogenic shock
5. Decompensated heart failure requiring treatment with intravenous loop diuretics
6. Known concomitant structural kidney disease such as polycystic kidney disease or renal artery stenosis