From the Guidelines
The recommended medication to add for this patient with heart failure with reduced ejection fraction (HFrEF) is ivabradine, as they have persistent symptoms of heart failure despite being on optimal guideline-directed medical therapy including an ACE inhibitor/ARB (Entresto), beta-blocker (carvedilol), mineralocorticoid receptor antagonist (spironolactone), diuretic (furosemide), and SGLT2 inhibitor (empagliflozine) 1.
Key Considerations
- The patient's left ventricular ejection fraction (LVEF) is 25%, which is below the threshold of 35% where ivabradine is recommended for patients with symptomatic heart failure, sinus rhythm, and elevated heart rates despite optimal medical therapy 1.
- Ivabradine is specifically indicated in this situation as it can further reduce heart rate without affecting blood pressure, which is crucial for patients with heart failure.
- The patient is already taking a beta-blocker (carvedilol), but ivabradine can be added to further reduce heart rate and improve symptoms.
Benefits of Ivabradine
- Reduces heart rate through inhibition of the If current in the sinoatrial node
- Decreases myocardial oxygen demand
- Improves diastolic filling time
- Has been shown to reduce hospitalizations in patients with symptomatic heart failure, sinus rhythm, and elevated heart rates despite optimal medical therapy 1
Other Options
- Other medications such as hydralazine and isosorbide dinitrate may be considered in certain situations, but they are not indicated in this specific clinical scenario without additional indications such as intolerance to ACE inhibitors/ARBs 1.
- Digoxin may be considered in symptomatic patients in sinus rhythm despite treatment with an ACE-I (or ARB), a beta-blocker and an MRA, to reduce the risk of hospitalization, but it is not the first choice in this scenario 1.
- An n-3 PUFA preparation may be considered in symptomatic HF patients to reduce the risk of cardiovascular hospitalization and cardiovascular death, but it is not a primary treatment for HFrEF 1.
From the FDA Drug Label
The Systolic Heart Failure Treatment with the I f Inhibitor Ivabradine Trial (SHIFT) was a randomized, double-blind trial comparing ivabradine and placebo in 6,558 adult patients with stable New York Heart Association (NYHA) class II to IV heart failure, left ventricular ejection fraction ≤ 35%, and resting heart rate ≥ 70 bpm Patients had to have been clinically stable for at least 4 weeks on an optimized and stable clinical regimen, which included maximally tolerated doses of beta-blockers and, in most cases, ACE inhibitors or ARBs, spironolactone, and diuretics, with fluid retention and symptoms of congestion minimized. Ivabradine benefit on the primary endpoint in SHIFT appeared to decrease as the dose of beta-blockers increased, with little if any benefit demonstrated in patients taking guideline-defined target doses of beta-blockers.
The patient is currently taking Carvedilol, a beta-blocker, and the dose is not specified as maximally tolerated or at the guideline-defined target dose. However, considering the patient's current medication regimen, which includes Carvedilol, Entresto (Sacubitril/Valsartan), Spironolactone, Furosemide, and Empagliflozin, and given the patient's symptoms of dyspnea on exertion and LVEF of 25%, Ivabradine could be considered as an add-on therapy to reduce the risk of hospitalization for worsening heart failure, as demonstrated in the SHIFT trial 2.
- The patient's heart rate is not provided, but if the patient has a resting heart rate ≥ 70 bpm, Ivabradine could be initiated at a dose of 5 mg twice daily, with the goal of maintaining a resting heart rate between 50 and 60 bpm, as tolerated.
- It is essential to monitor the patient's heart rate, blood pressure, and symptoms closely when adding Ivabradine to the treatment regimen.
From the Research
Medication Addition for HFrEF Patient
The patient in question has Heart Failure with Reduced Ejection Fraction (HFrEF) with a left ventricular ejection fraction (LVEF) of 25% and is experiencing dyspnea on exertion. The current treatment regimen includes Aspirin (ASA), Carvedilol, Entresto (Sacubitril/Valsartan), Spironolactone, Furosemide, and Empagliflozin.
Potential Medication Options
Based on the provided evidence, the following medication could be considered for addition to the treatment regimen:
- Ivabradine: This medication has been shown to improve symptoms, quality of life, and global assessment in patients with HFrEF and elevated heart rate despite guideline-directed medical therapy (GDMT) 3, 4, 5, 6.
Key Considerations
When considering the addition of ivabradine to the treatment regimen, the following points should be taken into account:
- The patient's heart rate: Ivabradine is most effective in patients with a heart rate above 70 bpm 4, 5, 6.
- The patient's current medication regimen: The patient is already taking a beta-blocker (Carvedilol), and the addition of ivabradine may have an additive effect on heart rate reduction 6.
- The potential benefits and risks of ivabradine: Ivabradine has been shown to improve symptoms and reduce hospitalization due to worsening HF, but it may also cause bradycardia, atrial fibrillation, and visual disturbances 3, 4, 5, 6.
Other Therapeutic Strategies
Other therapeutic strategies that may be considered for the management of HFrEF include:
- Quadruple therapy: The patient is already taking quadruple therapy, which includes a beta-blocker, angiotensin receptor/neprilysin inhibitor, sodium-glucose cotransporter 2 inhibitor, and mineralocorticoid receptor antagonist 7.
- Adjunctive symptomatic therapies: These may include medications such as digoxin and isosorbide dinitrate and hydralazine combination for African Americans 7.
- Novel medical therapies: These include vericiguat, omecamtiv mecarbil, genetic and cellular therapies, and mitochondria-targeted therapies, which are currently being evaluated in clinical trials 7.