People with heart failure with reduced ejection fraction (also called HFrEF or systolic heart failure) usually need to take several types of medicines. At first, this may involve 3 different medicines from 3 different drug classes: a diuretic, an agent that blocks the renin-angiotensin system (ACE inhibitor, ARB or ARNI), and a beta blocker.

• The most common drugs used to treat heart failure in patients with reduced ejection fraction include a diuretic; an angiotensin system blocker (angiotensin-converting enzyme [ACE] inhibitor, angiotensin receptor-neprilysin inhibitor [ARNI], OR angiotensin II receptor blocker [ARB]); and a beta blocker.
• Nitrates / hydralazine may be used alternatively in people who cannot tolerate an angiotensin system blocker. Other second-line agents may include SGLT2 inhibitors, digoxin or medicines to control your heart rhythm or rate.

Treatment goals for heart failure include:

• relieving symptoms like shortness of breath, fatigue, edema (fluid retention) and dizziness
• stopping, slowing or reversing worsening heart failure
• addressing risk factors like high blood pressure, diabetes, or metabolic syndrome with your healthcare team
• lowering the risk for complications such as arrhythmias (irregular heart beats), kidney disease, liver damage, hospitalization or death

Your doctor will determine which medicines are best for you based on your symptoms and heart failure classification, physical and history, previous treatments, imaging tests and lab work.

Drugs used to increase ejection fraction in HFrEF

Diuretics

• Diuretics ("water pills") increase urine production and decrease excess fluid, swelling and edema (fluid retention) in your body. Decreasing excess fluid can help you to breathe more easily.
• This class includes medicines like loop diuretics, thiazide diuretics, and aldosterone antagonists (potassium-sparing diuretics). In some cases, drug classes may need to be combined to help lower fluid excess.
• Loop diuretics, such as furosemide (Lasix), torsemide (Soaanz) or bumetanide (Bumex) are common first choice diuretics for HFrEF.
• Thiazide diuretics may include agents like chlorothiazide or chlorthalidone, but are not as strong as loop diuretics.
• Mineralocorticoid receptor antagonists (MRA) which are “potassium-sparing diuretics” include spironolactone (Aldactone, Carospir) and eplerenone (Inspra).
• Your doctor may need to closely monitor your blood levels of electrolytes, such as potassium, sodium, magnesium and calcium.

ACE inhibitors, ARBs or ARNI

• These medicines include angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor-neprilysin inhibitors (ARNI), and angiotensin II receptor blockers (ARB). You will typically only use only one of these medicines at a time.
• They are used to help lower blood pressure, improve blood flow and decrease the strain on your heart. They work by widening blood vessels.
• Examples of these drugs include the ACE inhibitors lisinopril (Zestril, Qbrelis, Prinivil), enalapril (Epaned, Vasotec), or captopril; the ARNI sacubitril-valsartan (Entresto), or the single agent ARBs like candesartan (Atacand), losartan (Cozaar) or valsartan (Diovan).
• ARBs may be an option if you cannot tolerate an ACE inhibitor.

Entresto is a newer combination of two medicines: the neprilysin inhibitor sacubitril and the angiotensin receptor blocker (ARB) valsartan. It is used for the treatment of patients with heart failure and reduced ejection fraction (HFrEF).

• It works by relaxing the blood vessels, improving blood flow and lowering stress on the heart.
• Entresto has been shown to lower the risk of cardiovascular death and hospitalization for heart failure.
• Entresto is usually given together with other heart failure medications, in place of an ACE inhibitor or ARB.

Learn more: Does Entresto improve ejection fraction?

Beta blockers

• Beta blockers help to slow your heart rate and reduce your blood pressure. They are often prescribed in conjunction with ACE inhibitors for heart failure.
• They also help to protect your heart from hormones that can be released in people with heart failure.
• Beta blocker examples used in heart failure include carvedilol (Coreg), metoprolol (Lopressor, Toprol XL, Kapspargo Sprinkle), and bisoprolol.

Other secondary agents

SGLT2 inhibitors

• Medicines in the SGLT2 (sodium-glucose cotransporter 2) inhibitor class are most often used to treat patients with type 2 diabetes to help control blood sugar and reduce kidney disease, but are also used in heart failure patients. They are not used in patients with type 1 diabetes.
• Examples include canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance) and ertugliflozin (Steglatro).

Hydralazine / isosorbide dinitrate (nitrate)

• This combination helps to relax and widen your blood vessels to ease blood flow throughout your body.
• They may be used in patients who cannot tolerate or use an ACE inhibitor, ARNI, or ARB. Nitrates / hydralazine may also be used in patients who need more advanced treatment.
• The medicines include hydralazine / isosorbide dinitrate, which can be bought as separate tablets or combined in one pill (BiDil), which may be more costly.

Digoxin (Lanoxin)

• This medication can help your heart to beat stronger and slower but is not typically used as an initial treatment.
• Digoxin may be added to your regimen if you have severe symptoms and ACE inhibitors or beta blockers have not helped.

Verquvo

• Verquvo (vericiguat) is a once-daily oral soluble guanylate cyclase (sGC) stimulator FDA-approved in Jan. 2021 to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for heart failure or need for outpatient IV diuretics. It is used in adults with symptomatic chronic HF and ejection fraction less than 45%.
• It works by increasing intracellular cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation and vasodilation.

Corlanor

• Corlanor (ivabradine) is used to treat adults who have chronic (lasting a long time) heart failure, with symptoms, to reduce their risk of hospitalization for worsening heart failure.
• Corlanor works by affecting the electrical activity of your heart in order to slow down the heart rate. It is not for use if you have symptoms of heart failure that recently worsened.

Other medicines, such as blood thinners or statins to lower cholesterol may be needed in some patients. Your doctor may suggest a cardiac rehabilitation program for you to increase the ability to exercise. Surgery, cardiac ventricular assist devices and a heart transplant are other options used to treat advanced heart failure.

What is an ejection fraction?

Ejection fraction is how well your heart chambers (the ventricles) can pump blood to your body to deliver oxygen and nutrients. A normal ejection fraction ranges from 50% to 70%.

• Patients with heart failure usually have an ejection fraction of 40% or less. This means that 40% or less of the amount of blood in the left ventricle of your heart is pumped out to your body with each contraction. The left ventricle is a lower chamber of your heart responsible for the main blood pumping action.
• If your left ventricle is weakened, as in heart failure, less blood and oxygen is pumped out of your heart when it contracts (during a heartbeat). Less oxygen can lead to symptoms like trouble exercising and shortness of breath.
• Your doctor can measure your ejection fraction using an echocardiogram (or "echo"), an imaging procedure that outlines your heart’s movements using an ultrasound machine.

Bottom Line

• People with heart failure who need to increase their ejection fraction usually need to take several different types of heart medicines.
• Initially, this may include 3 medicines from 3 different drug classes: a diuretic, an agent that blocks the renin-angiotensin system (ACE inhibitor, ARB or ARNI), and a beta blocker.
• Other medical treatments over the long-term may need to be added to treatment, as heart failure is a chronic (long-lasting) condition. Other nondrug treatments for advanced cases include surgery, cardiac ventricular assist devices or a heart transplant.