From the Guidelines
For a patient diagnosed with stage 3 Heart Failure with reduced Ejection Fraction (HFrEF), I recommend initiating a comprehensive medication regimen including an ACE inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist, as these have been shown to improve symptoms and reduce the risk of HF hospitalization and death 1.
Medication Regimen
The following medications are recommended:
- An ACE inhibitor (such as enalapril 2.5-20mg twice daily or lisinopril 10-40mg daily) to reduce the risk of HF hospitalization and death 1
- A beta-blocker (such as carvedilol 3.125-25mg twice daily or metoprolol succinate 25-200mg daily) to reduce the risk of HF hospitalization and death 1
- A mineralocorticoid receptor antagonist (spironolactone 25-50mg daily or eplerenone 25-50mg daily) to reduce the risk of HF hospitalization and death 1
Additional Therapies
For patients who remain symptomatic despite optimal treatment with an ACE inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist, consider adding:
- Sacubitril/valsartan (24/26mg to 97/103mg twice daily) in place of the ACE inhibitor after a 36-hour washout period to further reduce the risk of HF hospitalization and death 1
- Diuretics like furosemide (20-80mg daily or twice daily) for fluid overload symptoms to improve symptoms and exercise capacity 1
Lifestyle Modifications
Lifestyle modifications are also essential components of treatment, including:
- Sodium restriction (<2g daily)
- Fluid restriction if needed
- Regular physical activity
- Smoking cessation These modifications can help improve cardiac efficiency, reduce fluid retention, and decrease cardiac remodeling.
Monitoring and Titration
Medications should be titrated gradually to target doses while monitoring blood pressure, heart rate, renal function, and electrolytes to minimize adverse effects and optimize treatment outcomes.
From the FDA Drug Label
Sacubitril and valsartan contains a neprilysin inhibitor, sacubitril, and an angiotensin receptor blocker, valsartan. The cardiovascular and renal effects of sacubitril and valsartan in heart failure patients are attributed to the increased levels of peptides that are degraded by neprilysin, such as natriuretic peptides, by LBQ657, and the simultaneous inhibition of the effects of angiotensin II by valsartan In a 7-day valsartan-controlled study in patients with reduced ejection fraction (HFrEF), administration of sacubitril and valsartan resulted in a significant non-sustained increase in natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP compared to valsartan In PARADIGM-HF, sacubitril and valsartan decreased plasma NT-proBNP (not a neprilysin substrate) and increased plasma BNP (a neprilysin substrate) and urine cGMP compared with enalapril
Prescription for Stage 3 Heart Failure with Reduced Ejection Fraction (HFrEF):
- Sacubitril and valsartan can be considered for patients with HFrEF.
- The medication has been shown to decrease plasma NT-proBNP and increase plasma BNP and urine cGMP compared to enalapril in the PARADIGM-HF study.
- Key benefits of sacubitril and valsartan include simultaneous neprilysin inhibition and renin-angiotensin system blockade, which can help improve cardiovascular and renal effects in heart failure patients 2.
From the Research
Treatment Options for Stage 3 Heart Failure with Reduced Ejection Fraction (HFrEF)
The following treatment options are recommended for patients diagnosed with stage 3 HFrEF:
- Diuretics as the first-line drugs in the treatment of patients with HFrEF and volume overload 3
- Angiotensin-converting enzyme (ACE) inhibitors and β-blockers (carvedilol, sustained-release metoprolol succinate, or bisoprolol) should be used in treatment of HFrEF 3
- Use an angiotensin II receptor blocker (ARB) (candesartan or valsartan) if intolerant to ACE inhibitors because of cough or angioneurotic edema 3
- Sacubitril/valsartan may be used instead of an ACE inhibitor or ARB in patients with chronic symptomatic HFrEF class II or III to further reduce morbidity and mortality 3
- Add an aldosterone antagonist (spironolactone or eplerenone) in selected patients with class II-IV HF who can be carefully monitored for renal function and potassium concentration 3
- Add 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
- Ivabradine can be used in selected patients with HFrEF 3
Additional Treatment Considerations
- The four pillars of medical therapy in HFrEF include sodium-glucose co-transporter-2 inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and angiotensin-converting enzyme inhibitors or angiotensin receptor-nephrilysin inhibitors 4
- Angiotensin Receptor Neprilysin Inhibitor (ARNi), sodium glucose cotransport inhibitors (SGLTis), ivabradine, and Vericinguat are additional therapies for HFREF 5
- Renin angiotensin blockers (RAASbs) and beta blockers (BBs) have substantial effects in patients with HFREF and should remain the cornerstone of therapy 5
- ARNis are effective in further reducing adverse effects and should replace RAASbs in symptomatic HFREF patients 5
- SGLTis, Ivabradine, and Vericinguat should be considered in patients who remain symptomatic despite optimal doses of RAASbs/ARNis, MRAs, and BBs 5
Guideline-Directed Medical Therapy
- The 2021 European Society of Cardiology guidelines propose a new treatment algorithm for patients with HFrEF, defining the role of currently available drugs, interventions, and devices 6
- The new standard is a basic therapy consisting of four drugs with different mechanisms of action for all patients with HFrEF: an angiotensin-converting enzyme inhibitor, a beta-blocker, a mineralocorticoid antagonist, and a sodium glucose co-transporter-2 inhibitor 6
- Additional drugs and/or interventions/devices are indicated depending on the response to the four-drug basic therapy and the clinical phenotype 6