From the Guidelines
Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) should include four medication classes: renin-angiotensin-aldosterone system (RAS) inhibitors or angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid-receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors, as this combination has been shown to substantially extend survival, reduce hospitalization, and improve patient-reported quality of life 1. The core medications for GDMT in HFrEF include:
- RAS inhibitors or ARNI, such as sacubitril/valsartan
- Beta-blockers, particularly carvedilol, metoprolol succinate, or bisoprolol
- Mineralocorticoid receptor antagonists, such as spironolactone or eplerenone
- SGLT2 inhibitors, such as dapagliflozin or empagliflozin These medications should be initiated at low doses and gradually titrated to target doses as tolerated, with the goal of using all four core medication classes when possible 1. The use of these medications has been shown to reduce the risk of death by 73% over 2 years, and to extend life expectancy by 6 years in a 55-year-old patient with HFrEF 1. It is essential to note that despite strong clinical trial evidence and guideline recommendations, there continue to be significant gaps in the use of GDMT, with less than 10% of patients with HFrEF receiving all four core medication classes 1. Therefore, it is crucial to prioritize the use of GDMT in patients with HFrEF, and to implement strategies to improve adherence to these evidence-based treatments, such as in-hospital initiation of GDMT, simultaneous or rapid sequence initiation of GDMT, and participation in quality improvement registries 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. 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.
Guideline-Directed Medical Therapy (GDMT) for Heart Failure includes:
- ACE inhibitors (such as enalapril)
- ARBs (such as valsartan) for patients with HFrEF (Heart Failure with Reduced Ejection Fraction) to reduce morbidity and mortality. In patients who are intolerant of ACE inhibitors, ARBs may be used as an alternative. The choice of agent and dosing should be individualized based on patient-specific factors, such as kidney function and blood pressure. 2 3
From the Research
Definition of GDMT for Heart Failure
GDMT stands for Guideline-Directed Medical Therapy, which refers to the use of medications and treatments that are recommended by clinical guidelines for the management of heart failure with reduced ejection fraction (HFrEF) [ 4 ].
Components of GDMT for Heart Failure
The components of GDMT for HFrEF include:
- Beta-blockers (BB) [ 4 ]
- Angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), or angiotensin receptor-neprilysin inhibitors (ARNI) [ 4 ]
- Mineralocorticoid receptor antagonists (MRA) [ 4 ]
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors [ 5 ]
Benefits of GDMT for Heart Failure
The benefits of GDMT for HFrEF include:
- Reduced risk of death or heart failure hospitalizations [ 4 ]
- Improved survival [ 6 ]
- Reduced morbidity and mortality [ 5 ]
- Reduced risk of all-cause mortality [ 7 ]
Prevalence of GDMT for Heart Failure
The prevalence of GDMT for HFrEF varies, with studies reporting that: