Key Steps to Optimizing GDMT in Heart Failure

Dr Biykem Bozkurt outlines strategies for achieving guideline-directed medical therapy optimization.
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-TRANSCRIPT-
Hello. My name is Biykem Bozkurt. I'm a heart failure cardiologist, professor of medicine, senior dean of faculty, and director of Winters Center for Heart Failure Research at Baylor College of Medicine. Today, we're discussing tips for optimizing guideline-directed medical therapy (GDMT) in heart failure.
I want to talk about optimization strategies according to stages of heart failure in clear steps according to ejection fraction classification. In the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure, we have specific recommendations according to stages of heart failure. We revised the heart failure stage terminologies for these to be better understood by our patients and by nonspecialists.
The first stage in heart failure is patients with risk factors, such as diabetes, hypertension, coronary artery disease, and obesity, but without symptoms or signs or functional or structural cardiac abnormalities. We define this as stage A or at risk for heart failure.
The second stage is patients without symptoms or signs but with structural, functional, or biomarker abnormalities. This stage is called pre-heart failure or stage B. Patients with current or prior symptoms of heart failure are called stage C or symptomatic heart failure. Patients with advanced symptoms or signs with high-risk features, such as repeated hospitalizations or intolerance to GDMT, is defined as advanced heart failure or stage D.
We have specific recommendations for each stage. We also have a classification according to ejection fraction because of the existing evidence for treatment according to different ejection fraction classifications. Let's go over these ejection fraction classifications.
Patients with ejection fraction of 40% or less are classified as having heart failure with reduced ejection fraction, with ejection fraction between 41% and 49% as having mildly reduced ejection fraction, and with ejection fraction 50% or more as having preserved ejection fraction.
We also have a new category in the guidelines defined as heart failure with improved ejection fraction. These are patients with history of ejection fraction of 40% or less whose ejection fraction may have improved to more than 40% with treatment. These individuals need to be continued on GDMT despite resolution of symptoms or normalization of ejection fraction.
Let's go over the steps of GDMT in patients with symptomatic heart failure with reduced ejection fraction. The first step is initiation of quadruple therapy. This includes sodium-glucose cotransporter 2 (SGLT2) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and renin-angiotensin-aldosterone system (RAAS) inhibition, with either angiotensin receptor-neprilysin inhibitors (ARNIs) in patients with New York Heart Association (NYHA) class II-III or angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients with NYHA class II-IV heart failure.
These medications have been demonstrated to result in significant improvements in cardiovascular death and heart failure hospitalization as early as 30 days after initiation. Therefore, timely initiation is critical to prevent adverse outcomes.
Newer agents, such as ARNI and SGLT2 inhibitors, have beneficial effects also in the kidney. They slow the decline in estimated glomerular filtration rate and they also improve quality of life. They are effective not only in cardiovascular disease but also in renal outcomes and improving patient-reported outcomes. These medications are safe when compared with comparator or placebo and can be safely initiated predischarge.
Quadruple Therapy Initiation
In the guidelines, we specify that all four classes can be initiated simultaneously at low doses, or alternatively, these medications may be started sequentially. The sequence should be guided by clinical factors, not necessarily according to the historical way that the trials were conducted.
These medications can be initiated simultaneously without waiting to achieve optimal dose of the prior medication. In clinical practice, sequence can be individualized according to patient etiologies.
For example, in the outpatient setting, for a patient with active ischemia or tachycardia, beta-blockers may be prioritized. For a patient with advanced chronic kidney disease, SGLT2 inhibitors may be prioritized followed by ARNI. For a patient with significant congestion and NYHA class III symptoms with recurrent hospitalizations who has been treated with diuretics, SGLT2 inhibitors, ARNIs, and MRAs may be prioritized and then followed with beta-blockade.
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