Heart failure drug combo: start together or one at a time?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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 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) 8. If female, she must not be a woman of childbearing potential. That is, she must be: 1. Surgically sterilized (e.g., underwent hysterectomy, bilateral salpingectomy or bilateral oophorectomy) 2. Clinically diagnosed infertile 3. In a post-menopausal state, defined as no menses for 12 months without an alternative medical cause 9. 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: 1. Abstinence of heterosexual intercourse (when this is in line with preferred and usual lifestyle of the subject) 2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 3. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) 4. Intrauterine device 5. Intrauterine hormone-releasing system 6. Bilateral tubal occlusion 7. Vasectomized partner, who has received medical assessment of the surgical success, or clinically diagnosed infertile partner Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site) 2. Participation in another clinical study with an investigational product during the last month 3. Unwilling to sign inform consent 4. Patients with a known hypersensitivity or intolerance to ARNi or SGLT2i or any of the excipients 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 on investigator's judgement) 7. Previously confirmed cardiac amyloidosis 8. History of angioedema 9. 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 10. Female patients currently pregnant (confirmed by a positive pregnancy test) or intent to become pregnant or breast feeding 11. Severe valvulopathy according to the echocardiogram report 12. Previous history of ketoacidosis due to SGLT2i