Effectiveness and Safety of Uptitration of Guideline Directed MEdical Therapy in Heart Failure With Reduced Ejection Fraction With Limited Kidney Function Assessments

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

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

Exclusion criteria

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