Management of Heart Failure

Introduction to Heart Failure Management

• Heart failure with reduced ejection fraction (HFrEF) requires comprehensive management, including pharmacological and device-based therapies, to reduce cardiovascular death and hospitalization risk, as recommended by the American College of Cardiology and the European Society of Cardiology 1, 2, 3
• The European Society of Cardiology recommends SGLT2 inhibitors to lower the risk of heart failure hospitalization in patients with diabetes 4
• The combination of Entresto and SGLT2 inhibitors may provide complementary cardiorenal protection through different mechanisms 5

Patient Selection and Initiation of Entresto

• Patients with diabetes and HFrEF should be initiated on Entresto at a low dose and titrated gradually with careful monitoring of renal function and serum potassium, according to the American Heart Association 5
• Contraindications for Entresto include hypersensitivity to any component, history of angioedema related to previous ACE inhibitor or ARB therapy, concomitant use of ACE inhibitors, and concomitant use of aliskiren in patients with diabetes 5
• Patients with HFrEF (LVEF ≤40%) and NYHA functional class II-IV symptoms are eligible for Entresto therapy, particularly those who remain symptomatic despite optimal ACE inhibitor or ARB therapy for at least 3 months, as recommended by the American College of Cardiology 2, 6, 7
• Contraindications for Entresto therapy include history of angioedema, severe renal impairment (eGFR <30 mL/min/1.73m²), systolic blood pressure <100 mmHg, and current decompensated heart failure 6

Monitoring and Uptitration of Entresto

• Patients with diabetes and HFrEF have an increased risk of hyperkalemia with RAAS inhibitors, and monitoring recommendations include regular assessment of serum potassium levels, education to avoid over-the-counter potassium supplements, and limitation of high-potassium food and beverages, as suggested by the American College of Cardiology 5
• The target dose of Entresto is 97/103 mg twice daily, with careful monitoring for side effects, and gradual uptitration as tolerated, according to the European Society of Cardiology 5
• Patients should be monitored for warning signs, including unexplained changes in blood pressure, new or worsening edema, changes in heart rhythm, and increased fatigue or decreased exercise tolerance 8, 9

Renal Function and Hyperkalemia Considerations

• Temporary worsening of renal function may occur initially with Entresto, but doesn't necessarily indicate true tubular injury, as reported in the American Journal of Kidney Diseases 10
• Hyperkalemia risk is amplified by both diabetes and chronic kidney disease (CKD), requiring vigilant monitoring, and the triple combination of ACE inhibitor, ARB, and MRA is discouraged due to excessive hyperkalemia risk, as warned by the American Heart Association 5
• Patients with severe renal dysfunction (eGFR <30 mL/min/1.73m²) were excluded from major trials, so use of Entresto should be with caution in this population, as noted by the American College of Cardiology 5

Special Considerations and Concomitant Therapies

• Co-administration of Entresto and empagliflozin appears safe in terms of renal function in patients with HFrEF and diabetes, as reported in the European Heart Journal 4
• A multidisciplinary heart failure management program is recommended for patients with HFrEF, and Entresto can be combined with beta-blockers, MRAs, and SGLT2 inhibitors for comprehensive heart failure management, as recommended by the European Heart Journal and the American College of Cardiology 3, 6
• Device therapy (ICD, CRT) should still be considered based on guideline criteria for eligible patients 3
• The American College of Cardiology recommends considering Entresto in selected patients with HFpEF, particularly women and those with LVEF between 45-57% 11
• The following table summarizes the medication information:

Efficacy and Safety of Entresto

• Entresto is strongly recommended as a first-line therapy to replace ACE inhibitors or ARBs in patients with HFrEF to reduce cardiovascular death and hospitalization risk, with a strength of evidence based on high-quality evidence from large randomized controlled trials, such as the PARADIGM-HF trial 1, 2, 6, 12
• Entresto reduces the composite endpoint of cardiovascular death or heart failure hospitalization by 20% compared to enalapril, with similar benefits for both death and heart failure hospitalization components, in patients with HFrEF 2
• Entresto improved left ventricular function with a median LVEF increase from 28.2% to 37.8% after 12 months of therapy, as demonstrated in the PARADIGM-HF trial 6
• Angioedema has a comparable incidence to enalapril, according to the American College of Cardiology, and Entresto should not be used with other RAS inhibitors, including ACE inhibitors, ARBs, or aliskiren 1, 8
• The main risks of Entresto are symptomatic hypotension and angioedema, and patients should be monitored for warning signs, including unexplained changes in blood pressure, new or worsening edema, changes in heart rhythm, and increased fatigue or decreased exercise tolerance 8, 9