Heart failure & cardiomyopathiesTrial design
Design, Rationale, and Methods of the INITIATE-HFrEF Trial
- Randomized noninferiority trial
Study context
- Population
- Patients with heart failure with reduced ejection fraction (HFrEF)patients randomized · simultaneous 29 · sequential 33
- Participants
- Sixty-two patients
- Planned comparison
- simultaneous vs sequential initiation of angiotensin receptor-neprilysin inhibitors (ARNi) and SGLT2i in HFrEF
- simultaneousn = 29
- sequentialn = 33
- Primary endpoint
- composite of:
- Hypotension
- Hyperkalemia
- Hypokalemia
- Estimated glomerular filtration rate drop ≥50% from baseline
- Emergency visit for HF
- HF hospitalization
- Cardiovascular death
- Follow-up
- Approximately 24 weeks
No results yet. This paper sets out the design of a trial; its results are to come.
Baseline
Baseline characteristics
- mean age
- 68.1 ± 10.4 years
- men
- 65%
- inpatients
- 48%
- "de novo" HF diagnosis
- 79%
- prior treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers
- 39%
- prior beta-blockers
- 61%
- prior mineralocorticoid receptor antagonists
- 27%
- mean left ventricular ejection fraction
- 33% ± 9%
- systolic blood pressure
- 125.3 ± 17.4 mm Hg
- estimated glomerular filtration rate
- 78.1 ± 23.8 mL/min/1.73 m²
- serum potassium
- 4.3 ± 0.5 mmol/L
- Baseline characteristics were overall well balanced between groups
First agent in sequential group
- started on SGLT2i
- 27
- started on ARNi
- 6
Original publication
Design, Rationale, and Methods of the INITIATE-HFrEF Trial. JACC Adv. Published 4 February 2026. doi:10.1016/j.jacadv.2026.102589
Summarised from the published abstract; every number is checked against it