What is the role of Guideline-Directed Medical Therapy (GDMT) in chronic heart failure?

From the Guidelines

Guideline-directed medical therapy (GDMT) for chronic heart failure should include four key medication classes: ACE inhibitors or ARBs, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. The cornerstone medications are:

• ACE inhibitors (like lisinopril 10-40 mg daily or enalapril 2.5-20 mg twice daily) or ARBs (such as losartan 25-100 mg daily) if ACE inhibitors aren't tolerated
• Beta-blockers (carvedilol 3.125-25 mg twice daily, metoprolol succinate 12.5-200 mg daily, or bisoprolol 1.25-10 mg daily)
• Mineralocorticoid receptor antagonists (spironolactone 12.5-50 mg daily or eplerenone 25-50 mg daily)
• SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) These medications should be initiated at low doses and gradually titrated to target doses as tolerated, monitoring blood pressure, heart rate, renal function, and electrolytes. For patients with heart failure with reduced ejection fraction (HFrEF), all four medication classes are recommended, while treatment for heart failure with preserved ejection fraction (HFpEF) typically includes SGLT2 inhibitors and possibly other agents based on comorbidities. Key considerations for implementation include:
• Initiating GDMT in hospital and titrating rapidly to target doses 1
• Using multidisciplinary teams and virtual consults to support titration and monitoring 1
• Reducing cost-sharing and using electronic health record-based interventions to improve adherence 1
• Educating patients and providers about the benefits and risks of GDMT, and addressing concerns about tolerability and adverse events 1

From the FDA Drug Label

Heart Failure 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. The mortality benefit associated with enalapril does not appear to depend upon digitalis being present. A second multicenter trial used the SOLVD protocol for study of asymptomatic or minimally symptomatic patients SOLVD-Prevention patients, who had left ventricular ejection fraction ≤35% and no history of symptomatic heart failure, were randomized to placebo (n=2117) or enalapril (n=2111) and followed for up to 5 years.

Guideline-Directed Medical Therapy (GDMT) for Chronic Heart Failure: Enalapril is used in the treatment of heart failure. It has been shown to decrease systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure, and heart size, while increasing cardiac output and exercise tolerance.

• The medication has been associated with an 11 percent reduction in all-cause mortality and a 30 percent reduction in hospitalization for heart failure in patients with symptomatic heart failure and ejection fraction ≤35 percent.
• In asymptomatic or minimally symptomatic patients with left ventricular ejection fraction ≤35%, enalapril has been shown to reduce the risk of hospitalization for heart failure and development of symptoms of overt heart failure 2, 2.

From the Research

Guideline-Directed Medical Therapy (GDMT) for Chronic Heart Failure

The management of chronic heart failure, particularly heart failure with reduced ejection fraction (HFrEF), has seen significant advancements with the introduction of various pharmacological treatments.

• The use of ACE inhibitors has been well-established in reducing mortality, hospitalization, and symptoms, while increasing exercise capacity in patients with HFrEF 3.
• More recent studies have emphasized the importance of a combination of four medication classes: renin-angiotensin-neprilysin inhibitors, β-blockers, mineralocorticoid antagonists, and sodium-glucose cotransporter inhibitors, referred to as Foundational Therapy, in conferring rapid and robust reduction in both morbidity and mortality in most patients with HFrEF 4.
• The treatment approach for HFrEF involves the use of diuretics to relieve symptoms, and the application of disease-modifying drug and device therapies, with the goal of improving outcomes and reducing mortality 5.
• ACE inhibitors are part of first-line treatment for HFrEF, with benefits including reduced all-cause mortality, but also with potential adverse effects such as cough, hypotension, and hyperkalaemia 6.
• Recent updates in pharmacological treatment options for HFrEF recommend a combination of ACE inhibitors/angiotensin receptor-neprilysin inhibitor, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, with treatment initiation of all four drug classes being fast and simultaneous 7.

Key Components of GDMT for HFrEF

The key components of GDMT for HFrEF include:

• ACE inhibitors or angiotensin receptor-neprilysin inhibitors
• β-blockers
• Mineralocorticoid receptor antagonists
• SGLT2 inhibitors
• Diuretics for symptom relief
• Device therapies such as cardiac resynchronization therapy and implantable cardiac defibrillators in specific subpopulations.

Individualized Treatment Approach

Treatment of HFrEF should be individualized, taking into account patient-specific factors, comorbidities, and potential contraindications to certain medications. The treatment approach should also involve a multidisciplinary team, including healthcare providers, patients, and caregivers, to ensure optimal management and improved outcomes.