Comparative Assessment of Efficacy & Safety of Sacubitril/Valsartan Versus Ramipril in Patients With Renal Dysfunction Hospitalized With Acute Decompensated Heart Failure

Comparative Assessment of Efficacy & Safety of Sacubitril/Valsartan Versus Ramipril in Patients With Renal Dysfunction Hospitalized With Acute Decompensated Heart Failure - CAESAR (a Randomized Controlled Trial)

Sacubitril/valsartan is an established medication for heart failure. However, data still lags in its use in heart failure patients with chronic kidney disease. Sacubitril/valsartan is manufacturer-labeled for use in patients with eGFR < 30 ml/min/1.73 m2 at an initial dose of 24/26mg twice daily. However, to the best of our knowledge, the concept of sacubitril/valsartan or ACEi in patients with chronic kidney disease & presenting with decompensated heart failure has not yet been explored fully.

Inclusion Criteria: All the following should be met:

• Acute decompensated heart failure (ADHF)
• Left ventricular ejection fraction (LVEF) below 40%
• Renal dysfunction; defined as eGFR of 30mL/min/1.73m2 to less than 60mL/min/1.73m2 in relation to the level of urinary albumin/creatinine ratio (uACR) based on the 2024 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for the evaluation and management of CKD.
• A minimum blood pressure (BP) ≥ 105/60 mmHg.
• Independent of any inotropic or vasopressor support in the previous 24 hours before inclusion and randomization.
• No more than 72 hours had passed since admission to the heart failure unit.
• Patients should have had a New York Heart Association (NYHA) functional class II-IV, in addition to symptoms of volume overload at the time of presentation to the emergency room.

Exclusion Criteria:

• Patients who were on sacubitril/valsartan or ACEI/ angiotensin receptor blocker (ARB) before inclusion in the previous 12 months.
• Patients with AKI on presentation OR in the last 3 months OR had ≥ 2 hospital admissions in the last 12 months for AKI.
• History of known or suspected hypersensitivity, contraindications, or intolerance to any of the study drugs including ACEI, ARB or sacubitril (neprilysin inhibitor).
• Requirement for double treatment with both ACEI and ARB.
• Serum potassium (K+) level ≥ 5.0 mmol/L at randomization.
• A recent major adverse cardiovascular/cerebrovascular event within 1 month (acute coronary syndrome, stroke, transient ischemic attack, etc.).
• Patients with hemodynamically significant primary valvular lesion.
• Known hepatic impairment with a model for end-stage liver disease (MELD) score >10. 23
• History of malignancy of any organ system within the past year with a life expectancy < 1 year.