Initiation of ARNi and SGLT2i in Patients With HFrEF

Inclusion Criteria:

1. Age ≥ 18 years
2. Heart failure symptoms (NYHA II, III or IV)
3. Left ventricle ejection fraction ≤ 49% (assessed by transthoracic echocardiogram)
4. Glomerular filtration rate ≥ 25 ml/min/1.73m2 (CKD-EPI formula)
5. Serum potassium (K+) ≤ 5.4 mmol/L
6. Systolic blood pressure ≥ 100 mmHg
7. Not treated with ARNi nor with SGLT2i within the previous month (30 days beforeinclusion, except if initiated 5 days before randomization)
8. If female, she must not be a woman of childbearing potential. That is, she must be:
9. Surgically sterilized (e.g., underwent hysterectomy, bilateral salpingectomy orbilateral oophorectomy)
10. Clinically diagnosed infertile
11. In a post-menopausal state, defined as no menses for 12 months without analternative medical cause
12. If female patient of childbearing potential, she must have a negative serum pregnancytest at Visit 1 (Day 0) and must agree to consistently and correctly use (from 28 daysprior to first study treatment administration until at least 7 days after last studytreatment administration) one of the following highly effective methods ofcontraception:
13. Abstinence of heterosexual intercourse (when this is in line with preferred andusual lifestyle of the subject)
14. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
15. Combined (estrogen and progestogen containing) hormonal contraception associatedwith inhibition of ovulation (oral, intravaginal, transdermal)
16. Intrauterine device
17. Intrauterine hormone-releasing system
18. Bilateral tubal occlusion
19. Vasectomized partner, who has received medical assessment of the surgicalsuccess, or clinically diagnosed infertile partner

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both Investigatorstaff and/or staff at the study site)
2. Participation in another clinical study with an investigational product during thelast month
3. Unwilling to sign inform consent
4. Patients with a known hypersensitivity or intolerance to ARNi or SGLT2i or any of theexcipients of the products
5. Hospitalization due to non-cardiovascular causes, surgical procedure, coronary,cerebral or peripheral vascular events or sepsis in the prior month
6. Cancer (life limiting with an estimated life expectancy of less than 2 years based oninvestigator's judgement)
7. Previously confirmed cardiac amyloidosis
8. History of angioedema
9. Implantable cardioverter-defibrillators or cardiac resynchronization therapy within 3months prior to screening or if there is an intent to implant either device in the 3months following screening
10. Female patients currently pregnant (confirmed by a positive pregnancy test) or intentto become pregnant or breast feeding
11. Severe valvulopathy according to the echocardiogram report
12. Previous history of ketoacidosis due to SGLT2i