What is the Guideline-Directed Medical Therapy (GDMT) for patients with Heart Failure with Reduced Ejection Fraction (HFrEF)?

From the Guidelines

Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) should include the initiation and optimization of four foundational medication classes: angiotensin receptor-neprilysin inhibitors (ARNIs) or angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. The goal of GDMT is to reduce mortality, hospitalizations, and symptoms by addressing the neurohormonal activation, fluid retention, and maladaptive remodeling that characterize HFrEF.

• Key medication classes include:
  • ARNIs, such as sacubitril/valsartan, or alternatively ACEIs like lisinopril or enalapril, or angiotensin receptor blockers (ARBs) such as losartan or valsartan
  • Beta-blockers, including carvedilol, metoprolol succinate, or bisoprolol
  • MRAs, such as spironolactone or eplerenone
  • SGLT2 inhibitors, like empagliflozin or dapagliflozin These medications should be initiated at low doses and uptitrated to target doses as tolerated, with close monitoring of blood pressure, heart rate, renal function, and electrolytes, as outlined in the 2020 ACC/AHA clinical performance and quality measures for adults with heart failure 1. Additional therapies may include diuretics for symptom relief, ivabradine for patients with persistent heart rates above 70 bpm despite maximally tolerated beta-blocker therapy, and hydralazine/isosorbide dinitrate particularly in African American patients, as recommended by the 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 1. Regular follow-up every 2-4 weeks during medication initiation and uptitration is essential to monitor for side effects and ensure optimal dosing, as emphasized in the 2020 ACC/AHA clinical performance and quality measures for adults with heart failure 1.

From the FDA Drug Label

Sacubitril and valsartan tablets are indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction. The Guideline-Directed Medical Therapy (GDMT) for patients with Heart Failure with Reduced Ejection Fraction (HFrEF) includes sacubitril and valsartan tablets to reduce the risk of cardiovascular death and hospitalization for heart failure.

• The recommended starting dose is 49/51 mg orally twice-daily, and the dose should be doubled after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient 2.

From the Research

Guideline-Directed Medical Therapy (GDMT) for HFrEF

The Guideline-Directed Medical Therapy (GDMT) for patients with Heart Failure with Reduced Ejection Fraction (HFrEF) includes:

• Identification and treatment of underlying and precipitating causes of heart failure 3
• Use of diuretics as first-line drugs in the treatment of patients with HFrEF and volume overload 3
• Treatment with angiotensin-converting enzyme (ACE) inhibitors, β-blockers, and angiotensin II receptor blockers (ARBs) 3, 4, 5, 6
• Use of sacubitril/valsartan instead of an ACE inhibitor or ARB in patients with chronic symptomatic HFrEF class II or III 3, 5, 6
• Addition of an aldosterone antagonist in selected patients with class II-IV HF 3
• Use of isosorbide dinitrate plus hydralazine in patients self-described as African Americans with class II-IV HF being treated with diuretics, ACE inhibitors, and β-blockers 3, 5
• Use of ivabradine in selected patients with HFrEF 3, 5, 7
• Quadruple therapy consisting of β-blockers, angiotensin receptor/neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, and mineralocorticoid receptor antagonists as first-line treatment 4, 5

Device Therapy for HFrEF

Device therapy for HFrEF includes:

• Implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) 7
• CRT as the therapy of choice in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology 7
• Alternative electrical therapies such as baroreflex activation therapy (BAT) and cardiac contractility modulation (CCM) for patients not candidates for CRT 7
• Mitraclip for significant mitral valve regurgitation, ablation in specific atrial fibrillation cases, and omecamtiv mecarbil as options under evaluation in clinical trials 5
• The HeartMate 3 magnetically levitated centrifugal left ventricular assist device (LVAD) as an option for stage D HF patients who are candidates for an LVAD 5