Heart failure is a chronic condition that significantly impacts the quality of life and overall health of millions worldwide.
Management of heart failure typically involves a combination of lifestyle changes, medications, and sometimes surgical interventions. Among the medications, Entresto (sacubitril/valsartan) has been widely prescribed due to its proven efficacy in reducing hospitalization and mortality rates among heart failure patients. However, not all patients can tolerate Entresto due to side effects, contraindications, or financial constraints. Therefore, exploring alternatives to Entresto is essential for providing comprehensive care to heart failure patients.
What Is Entresto?
Entresto is a combination medication that includes sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker (ARB). This dual mechanism of action helps to reduce strain on the heart by dilating blood vessels, reducing sodium retention, and enhancing the heart’s pumping ability. Entresto is primarily prescribed for patients with heart failure with reduced ejection fraction (HFrEF), where the heart muscle does not contract effectively, and the ejection fraction is significantly lower than normal.
Despite its benefits, some patients may experience adverse reactions to Entresto, such as hypotension, hyperkalemia, renal impairment, or angioedema. Additionally, the cost of Entresto may be prohibitive for some patients, necessitating the need for alternative treatment options.
Alternatives to Entresto
1. ACE Inhibitors (Angiotensin-Converting Enzyme Inhibitors)
ACE inhibitors are a cornerstone in the treatment of heart failure. They work by inhibiting the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thus lowering blood pressure and reducing the workload on the heart.
Common ACE Inhibitors:
Lisinopril: Often prescribed for heart failure, lisinopril helps to relax blood vessels and improve blood flow, making it easier for the heart to pump.
Enalapril: Enalapril has been extensively studied and shown to reduce symptoms of heart failure, improve exercise tolerance, and decrease the need for hospitalization.
Ramipril: Known for its efficacy in reducing cardiovascular events in heart failure patients, ramipril is another widely used ACE inhibitor.
Advantages and Disadvantages:
ACE inhibitors are generally well-tolerated, but they can cause side effects such as cough, hyperkalemia, and, rarely, angioedema. Patients with renal impairment may require careful monitoring and dose adjustments.
see also: What Are The Best Medications for Heart Failure?
2. ARBs (Angiotensin II Receptor Blockers)
ARBs, like valsartan (a component of Entresto), are another option for patients who cannot tolerate ACE inhibitors. ARBs block the action of angiotensin II directly at its receptor sites, leading to vasodilation and reduced blood pressure.
Common ARBs:
Losartan: Effective in reducing blood pressure and improving heart failure symptoms, losartan is often used as an alternative to ACE inhibitors.
Candesartan: Clinical trials have shown candesartan to be effective in reducing hospitalizations and mortality in heart failure patients.
Irbesartan: Known for its renal protective effects, irbesartan is often prescribed to heart failure patients, especially those with coexisting diabetic nephropathy.
Advantages and Disadvantages:
ARBs are usually well-tolerated and have a lower incidence of cough compared to ACE inhibitors. However, they can still cause hyperkalemia and renal impairment, necessitating regular monitoring.
3. Beta-Blockers
Beta-blockers are essential in the management of heart failure as they reduce the heart rate, decrease myocardial oxygen demand, and improve overall cardiac function.
Common Beta-Blockers:
Carvedilol: This non-selective beta-blocker with alpha-blocking properties has been shown to improve survival and reduce hospitalizations in heart failure patients.
Metoprolol Succinate: A selective beta-1 blocker, metoprolol succinate helps to improve heart function and reduce symptoms in heart failure patients.
Bisoprolol: Another selective beta-1 blocker, bisoprolol is effective in improving symptoms and reducing mortality in heart failure patients.
Advantages and Disadvantages:
Beta-blockers can cause bradycardia, hypotension, and fatigue, particularly when treatment is initiated. They are typically introduced at low doses and gradually titrated to the target dose to minimize side effects.
4. Mineralocorticoid Receptor Antagonists (MRAs)
MRAs, also known as aldosterone antagonists, block the effects of aldosterone, a hormone that can contribute to fluid retention and worsening heart failure.
Common MRAs:
Spironolactone: Effective in reducing morbidity and mortality in heart failure patients, spironolactone also helps to manage fluid retention.
Eplerenone: Similar to spironolactone but with fewer side effects such as gynecomastia, eplerenone is another option for managing heart failure.
Advantages and Disadvantages:
MRAs can cause hyperkalemia and renal impairment, requiring regular monitoring of kidney function and electrolyte levels.
They are particularly beneficial in patients with advanced heart failure.
5. Diuretics
Diuretics are used to manage fluid overload in heart failure patients.
They help to reduce symptoms such as edema and shortness of breath by promoting the excretion of excess fluid.
Common Diuretics:
Furosemide: A loop diuretic commonly used to manage fluid retention in heart failure patients.
Bumetanide: Similar to furosemide but with a more potent diuretic effect, often used in patients who require more aggressive fluid management.
Hydrochlorothiazide: A thiazide diuretic used in combination with other diuretics to manage fluid retention.
Advantages and Disadvantages:
Diuretics are effective in relieving symptoms of fluid overload but can cause electrolyte imbalances, dehydration, and renal impairment. Careful monitoring and dose adjustments are essential.
6. SGLT2 Inhibitors
Originally developed for the treatment of type 2 diabetes, SGLT2 inhibitors have shown significant benefits in heart failure patients, including those without diabetes.
Common SGLT2 Inhibitors:
Dapagliflozin: Proven to reduce hospitalizations and cardiovascular deaths in heart failure patients, dapagliflozin is a promising addition to heart failure therapy.
Empagliflozin: Similar to dapagliflozin, empagliflozin has shown benefits in improving heart failure outcomes.
Advantages and Disadvantages:
SGLT2 inhibitors are generally well-tolerated but can cause urinary tract infections and genital infections. They are particularly beneficial in heart failure patients with coexisting diabetes.
7. Ivabradine
Ivabradine selectively inhibits the If current in the sinoatrial node, reducing heart rate without affecting blood pressure. It is particularly useful in patients with heart failure and a resting heart rate above 70 beats per minute despite optimal beta-blocker therapy.
Advantages and Disadvantages:
Ivabradine can cause visual disturbances and bradycardia. It is typically used as an adjunctive therapy in patients who are already on standard heart failure medications.
8. Digoxin
Digoxin is a cardiac glycoside that increases the force of myocardial contraction and has a modest effect on heart rate. It is used in patients with heart failure and atrial fibrillation or those who remain symptomatic despite optimal therapy.
Advantages and Disadvantages:
Digoxin can cause toxicity, especially in the elderly and those with renal impairment. Symptoms of digoxin toxicity include nausea, vomiting, and arrhythmias. Regular monitoring of digoxin levels is essential.
9. Hydralazine and Isosorbide Dinitrate
This combination therapy is particularly beneficial in African American patients with heart failure. Hydralazine works as a vasodilator, while isosorbide dinitrate helps to reduce preload and afterload.
Advantages and Disadvantages:
This combination can cause headaches, dizziness, and hypotension. It is typically used in patients who cannot tolerate ACE inhibitors or ARBs or as an add-on therapy.
Conclusion
While Entresto remains a highly effective medication for managing heart failure, several alternatives are available for patients who cannot tolerate it or for whom it is not suitable. ACE inhibitors, ARBs, beta-blockers, MRAs, diuretics, SGLT2 inhibitors, ivabradine, digoxin, and the combination of hydralazine and isosorbide dinitrate all offer viable options for managing heart failure. The choice of alternative therapy should be individualized based on the patient’s specific condition, comorbidities, and potential for adverse effects.