Initiation of ARNi and SGLT2i in Patients With HFrEF

Prior treatment

• Participation in another clinical study with an investigational product during the last month
• Hospitalization due to non-cardiovascular causes, surgical procedure, coronary, cerebral or peripheral vascular events or sepsis in the prior month
• Previously confirmed cardiac amyloidosis
• Implantable cardioverter-defibrillators or cardiac resynchronization therapy within 3 months prior to screening or if there is an intent to implant either device in the 3 months following screening
• Previous history of ketoacidosis due to SGLT2i

Other illness

• Patients with a known hypersensitivity or intolerance to ARNi or SGLT2i or any of the excipients of the products
• Cancer (life limiting with an estimated life expectancy of less than 2 years based on investigator's judgement)
• History of angioedema

Other

• Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
• Unwilling to sign inform consent
• Female patients currently pregnant (confirmed by a positive pregnancy test) or intent to become pregnant or breast feeding
• Severe valvulopathy according to the echocardiogram report

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