What is guideline-directed therapy in heart failure?

From the Guidelines

Guideline-directed therapy for heart failure involves a comprehensive medication regimen that includes four medication classes: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) as stated in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

Key Medications

• ACEIs or ARBs are used as first-line therapy, with ARNIs as an alternative for patients who can tolerate them
• Beta-blockers are essential for all patients with heart failure, unless contraindicated
• MRAs are added for patients with reduced ejection fraction
• SGLT2i are now recommended for all patients with heart failure, regardless of diabetes status, as they have been shown to reduce mortality and improve quality of life 1

Additional Therapies

• Diuretics such as furosemide are used for symptom relief from fluid overload
• Ivabradine may be added for heart rate control in advanced cases
• Hydralazine with isosorbide dinitrate is particularly beneficial in African American patients

Implementation and Monitoring

• Therapy should be initiated at low doses and gradually titrated up to target doses as tolerated
• Regular monitoring of renal function, electrolytes, and blood pressure is necessary to adjust therapy as needed
• Despite the highest quality evidence supporting the use of guideline-directed medical therapies, implementation remains suboptimal, with less than 10% of patients with HFrEF receiving all recommended therapies 1

Special Considerations

• Patients with improved left ventricular ejection fraction (LVEF) should continue their previous heart failure treatment
• New recommendations have been made for the treatment of heart failure with preserved ejection fraction (HFpEF), including the use of SGLT2i, MRAs, and ARNIs 1
• Value statements have been created for select recommendations to guide cost-effective treatment decisions 1

From the FDA Drug Label

The Valsartan Heart Failure Trial (Val-HeFT) was a multinational, double-blind study in which 5,010 patients with NYHA class II (62%) to IV (2%) heart failure and LVEF less than 40%, on baseline therapy chosen by their physicians, were randomized to placebo or valsartan (titrated from 40 mg twice daily to the highest tolerated dose or 160 mg twice daily) and followed for a mean of about 2 years. Although Val-HeFT’s primary goal was to examine the effect of valsartan when added to an ACE inhibitor, about 7% were not receiving an ACE inhibitor. Other background therapy included diuretics (86%), digoxin (67%), and beta-blockers (36%).

Guideline-directed therapy in heart failure involves the use of medications such as:

• ACE inhibitors
• Beta-blockers
• Diuretics
• Angelon receptor blockers (ARBs) like valsartan, as seen in the Val-HeFT trial 2 These therapies are used to manage heart failure and reduce morbidity and mortality.

From the Research

Definition of Guideline-Directed Therapy

• Guideline-directed medical therapy (GDMT) is the cornerstone of pharmacological therapy for patients with heart failure with reduced ejection fraction (HFrEF) 3
• GDMT consists of the four main drug classes: renin-angiotensin system inhibitors, evidence-based β-blockers, mineralocorticoid inhibitors, and sodium glucose cotransporter 2 inhibitors 3

Benefits of Guideline-Directed Therapy

• GDMT reduces mortality and hospitalizations in adults with HFrEF 4
• The effect of GDMT is most beneficial when medications from the four main drug classes are used in conjunction 3
• GDMT has been shown to improve clinical outcomes, including ejection fraction, 6-minute walk distance, and quality of life 4

Implementation of Guideline-Directed Therapy

• Despite its benefits, there is an underutilization of GDMT, partially due to lack of awareness of how to safely and effectively initiate and titrate these medications 3
• The development of heart failure clinics achieving optimal GDMT is crucial to improve outcomes for HFrEF patients 4
• Hospitalization due to heart failure progression is an opportunity to titrate GDMT among patients with HFrEF 5, 6
• Team-based care and medication optimization clinics can help overcome financial barriers to optimal GDMT 7

Key Components of Guideline-Directed Therapy

• Renin-angiotensin system inhibitors (RASi), including ACE inhibitors, ARBs, and ARNI 3, 6
• Evidence-based β-blockers (βBs) 3, 6
• Mineralocorticoid inhibitors (MRAs) 3, 6
• Sodium glucose cotransporter 2 inhibitors (SGLT2i) 3, 6