What is the goal-directed medical therapy for heart failure?

From the Guidelines

Goal-directed medical therapy for heart failure should include a combination of 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 approach has been shown to substantially extend survival, reduce hospitalization, and improve patient-reported quality of life 1. The cornerstone medications for heart failure with reduced ejection fraction (HFrEF) include:

• Angiotensin-converting enzyme inhibitors (ACEIs) like lisinopril (10-40 mg daily) or angiotensin receptor blockers (ARBs) such as losartan (50-150 mg daily) if ACEIs aren't tolerated
• Beta-blockers, with carvedilol (3.125-25 mg twice daily), metoprolol succinate (12.5-200 mg daily), or bisoprolol (1.25-10 mg daily) being preferred options
• Mineralocorticoid receptor antagonists like spironolactone (25-50 mg daily) or eplerenone (25-50 mg daily) for patients with ejection fraction ≤35%
• SGLT2 inhibitors such as dapagliflozin (10 mg daily) or empagliflozin (10 mg daily) for patients with persistent symptoms despite these medications Diuretics like furosemide (20-80 mg daily or twice daily) are used for symptom relief but don't improve mortality. These medications work by blocking harmful neurohormonal pathways that contribute to cardiac remodeling, reducing cardiac workload, improving ventricular function, and enhancing sodium and fluid excretion. Medication doses should be started low and gradually titrated to target doses as tolerated, with regular monitoring of blood pressure, heart rate, renal function, and electrolytes to ensure safety and efficacy 1. Implementation strategies such as in-hospital initiation of GDMT, simultaneous or rapid sequence initiation of GDMT, participation in quality improvement registries, multidisciplinary titration clinics, virtual consult teams, reduction of cost-sharing, remote algorithm-based medication optimization, electronic health record-based interventions, and direct-to-patient educational initiatives can help bridge gaps in the delivery of evidence-based care 1. The use of these strategies can help improve patient outcomes, reduce hospitalizations, and enhance quality of life for individuals with heart failure.

From the FDA Drug Label

The Randomized Spironolactone Evaluation Study was a placebo controlled, double-blind study of the effect of spironolactone on mortality in patients with highly symptomatic heart failure and reduced ejection fraction Spironolactone reduced the risk of death by 30% (p< 0. 001; 95% confidence interval 18% to 40%). Spironolactone also reduced the risk of hospitalization for cardiac causes (defined as worsening heart failure, angina, ventricular arrhythmias, or myocardial infarction) by 30% (p < 0. 001; 95% confidence interval 18% to 41%). Spironolactone tablets are indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure.

The goal of directed medical therapy for heart failure with spironolactone is to increase survival, manage edema, and reduce the need for hospitalization for heart failure. The medication has been shown to reduce the risk of death and hospitalization for cardiac causes by 30% in patients with highly symptomatic heart failure and reduced ejection fraction 2. Spironolactone is usually administered in conjunction with other heart failure therapies 2. Key benefits of spironolactone include:

• Reduced risk of death
• Reduced risk of hospitalization for cardiac causes
• Increased survival
• Management of edema The medication is indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction 2.

From the Research

Goal-Directed Medical Therapy for Heart Failure

• The primary goal of medical therapy for heart failure with reduced ejection fraction (HFrEF) is to improve symptoms, reduce morbidity and mortality, and enhance quality of life 3, 4, 5, 6, 7.
• Treatment strategies for HFrEF involve the use of evidence-based medications, including beta-blockers, angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), and sacubitril/valsartan, among others 3, 4, 5, 6, 7.

Medication Therapy

• Beta-blockers are a cornerstone in the management of HFrEF, as they can reverse the neurohumoral effects of the sympathetic nervous system, leading to prognostic and symptomatic benefits 3.
• ACEi and ARB are also essential in the treatment of HFrEF, as they can reduce mortality and morbidity by counteracting the renin-angiotensin-aldosterone system 6, 7.
• Sacubitril/valsartan, a combination of an ARB and a neprilysin inhibitor, has been shown to improve outcomes in patients with HFrEF and can be used in place of an ACEi or ARB 6.
• SGLT2 inhibitors, such as dapagliflozin, have also been found to be beneficial in reducing mortality and morbidity in patients with HFrEF 6.

Individualized Treatment Approach

• A comprehensive approach to treating HFrEF involves individualizing therapy based on the patient's clinical profile, including congestion, blood pressure, heart rate, renal function, and electrolytes 5.
• The selection of specific medications and dosages should be tailored to the patient's needs, taking into account comorbidities and potential drug-disease interactions 3, 5.
• Regular monitoring and adjustment of medication therapy are crucial to optimize treatment outcomes and minimize adverse effects 4, 5.

Evidence-Based Guidelines

• Current guidelines recommend the use of ACEi, ARB, beta-blockers, and sacubitril/valsartan in the treatment of HFrEF, with a focus on titrating medications to optimal doses and monitoring for potential side effects 3, 4, 6, 7.
• The European Society of Cardiology, Canadian Cardiovascular Society, and American College of Cardiology Heart Failure guidelines all support the use of these medications in the management of HFrEF 6.