What are the highlights of goal-directed medical therapy for congestive heart failure (CHF) with reduced ejection fraction (HFrEF), specifically for patients with a left ventricular ejection fraction (LVEF) of 35 to 40%?

From the Guidelines

Goal-directed medical therapy for systolic heart failure with an ejection fraction (EF) of 35-40% should prioritize the use of ACE inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors to improve symptoms, reduce hospitalizations, and extend life. The cornerstone medications include ACE inhibitors (or ARNIs) such as lisinopril (10-40 mg daily) or sacubitril/valsartan (24/26 mg to 97/103 mg twice daily) for patients with persistent symptoms 1.

• Add a beta-blocker such as carvedilol (3.125-25 mg twice daily), metoprolol succinate (25-200 mg daily), or bisoprolol (1.25-10 mg daily) to reduce the risk of HF hospitalization and death 1.
• Include a mineralocorticoid receptor antagonist like spironolactone (25-50 mg daily) or eplerenone (25-50 mg daily) to reduce the risk of HF hospitalization and death 1.
• An SGLT2 inhibitor such as dapagliflozin (10 mg daily) or empagliflozin (10 mg daily) should also be added to reduce the risk of HF hospitalization and death, although this is not explicitly mentioned in the provided guidelines, it is a recent recommendation based on other studies.
• Diuretics like furosemide (20-80 mg daily or twice daily) help manage fluid overload but don't improve mortality 1. These medications work by reducing cardiac workload, inhibiting harmful neurohormonal activation, promoting beneficial cardiac remodeling, and improving cardiac efficiency.
• Careful monitoring of blood pressure, renal function, and electrolytes is essential, with medication doses titrated gradually to target doses as tolerated 1. It is also important to consider the use of ivabradine in patients with a heart rate ≥70 bpm despite optimal beta-blocker therapy, and hydralazine-nitrate therapy in patients who cannot tolerate ACE inhibitors or ARBs 1.
• The use of ARNIs, such as sacubitril/valsartan, is recommended as a replacement for ACE inhibitors in ambulatory patients who remain symptomatic despite optimal treatment with ACE inhibitors, beta-blockers, and MRAs 1.

From the FDA Drug Label

In trials in patients treated with digitalis and diuretics, treatment with enalapril resulted in decreased systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure and heart size, and increased cardiac output and exercise tolerance. Heart Failure, Mortality Trials In a multicenter, placebo-controlled clinical trial, 2,569 patients with all degrees of symptomatic heart failure and ejection fraction ≤35 percent were randomized to placebo or enalapril and followed for up to 55 months (SOLVD-Treatment) Use of enalapril was associated with an 11 percent reduction in all-cause mortality and a 30 percent reduction in hospitalization for heart failure.

The goal-directed medical therapy for congestive heart failure, systolic, with an EF of 35 to 40% includes:

• Decreasing systemic vascular resistance and blood pressure
• Increasing cardiac output and exercise tolerance
• Reducing hospitalization for heart failure
• Improving survival Key points of the therapy are:
• Use of enalapril in combination with digitalis and diuretics
• Monitoring of patients to adjust treatment as needed
• Lifestyle modifications to reduce symptoms and slow disease progression 2, 2, 2

From the Research

Goal-Directed Medical Therapy for Congestive Heart Failure

The goal-directed medical therapy for congestive heart failure, systolic, with an EF of 35 to 40% includes several key components:

• Beta-blockers: to reduce mortality and hospitalization rates 3
• Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs): to reduce mortality and hospitalization rates, and to improve symptoms 3, 4, 5
• Diuretics: to manage fluid overload and improve symptoms 3
• Aldosterone antagonists: to reduce mortality and hospitalization rates 3
• Ivabradine: to reduce hospitalization rates in patients with heart rates >70 bpm 3
• Devices: such as automatic implantable cardioverter defibrillators (AICDs) and cardiac resynchronization therapy (CRT) to reduce mortality and hospitalization rates 3
• Digoxin: to improve symptoms and exercise tolerance 3

Treatment Considerations

When treating patients with congestive heart failure, systolic, with an EF of 35 to 40%, it is essential to consider the following:

• The use of ACE inhibitors has been shown to be beneficial in patients with heart failure and preserved ejection fraction, with a trend towards lower risk of death and delayed time to hospital readmission 4
• The role of ACE inhibitors in patients with heart failure and preserved ejection fraction remains unclear, but studies suggest a modest improvement in the composite end point of total mortality or heart failure hospitalization 5
• Patients with obesity, hypertension, atrial fibrillation, and volume overload require aggressive management, including weight reduction, exercise programs, and diuretics 6
• Coronary revascularization should be considered in patients with significant coronary heart disease 6

Patient Characteristics

Patients with congestive heart failure, systolic, with an EF of 35 to 40% often have the following characteristics:

• Increased age: with a higher frequency of heart failure in older patients 7
• Comorbid conditions: such as hypertension, ischemic heart disease, atrial fibrillation, obesity, diabetes mellitus, renal disease, or obstructive lung disease 6, 7
• Functional limitations: with a higher proportion of patients having New York Heart Association classes III and IV 7