Angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and angiotensin receptor neprilysin inhibitors (ARNIs) can treat systolic heart failure. A doctor may also suggest beta-blockers, diuretics, or other medications.

Systolic heart failure occurs when the heart’s left ventricle cannot pump enough blood for the body’s needs.

The percentage of blood the left ventricle pumps with each heartbeat is called ejection fraction (EF). A typical EF is 55–70%.

Systolic heart failure has an EF of 40% or less. It is also known as heart failure with reduced ejection fraction (HFrEF). Medication is one type of treatment for HFrEF.

This article discusses the goal of medications and summarizes the available options.

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Heart failure is typically a chronic condition that worsens over time. However, medication is one of the treatments that can help.

The goal of medications is to:

  • slow heart failure progression
  • ease symptoms
  • extend life span
  • improve quality of life
  • reduce the frequency of hospitalizations

Medication for systolic heart failure can help by:

  • improving the heart’s ability to pump
  • widening blood vessels
  • reducing sodium and water in the body

“First-line” is the term that describes the first treatment or therapy doctors prescribe for a disease or condition.

According to 2022 treatment guidelines from the American Heart Association, American College of Cardiology, and Heart Failure Society of America, first-line therapy for people with HFrEF should include one of the following:

  • angiotensin converting enzyme (ACE) inhibitor
  • angiotensin receptor blocker (ARB)
  • angiotensin receptor neprilysin inhibitor (ARNI)

ACE inhibitors reduce the workload on the heart muscle and make it easier for the heart to pump blood. They also decrease blood pressure.

An ACE inhibitor is a type of vasodilator medication, which means it prevents blood vessels from narrowing. It does this by blocking the protein called angiotensin from converting to angiotensin ll, which can narrow blood vessels.


Doctors usually prescribe an oral version of ACE inhibitor medication, but they can also administer it using an intravenous (IV) line.

The dosage can depend on the specific ACE inhibitor:

Initial daily dose in milligrams (mg)Target dosage
captopril6.25 mg, three times daily50 mg, three times daily
enalapril2.5 mg, twice daily10–20 mg, twice daily
fosinopril5–10 mg, once daily40 mg, once daily
lisinopril2.5–5 mg, once daily20–40 mg, once daily
quinapril5 mg, twice daily20 mg, twice daily
perindopril2 mg, once daily8–16 mg, once daily
trandolapril1 mg, once daily4 mg, once daily
ramipril1.25–2.5 mg, once daily10 mg, once daily

Side effects and considerations

ACE inhibitor side effects are uncommon and usually minor.

Some side effects may include:

  • dry cough, which is one of the most common side effects
  • low blood pressure
  • dizziness
  • fainting
  • high potassium levels (hyperkalemia)
  • increased creatinine and blood urea nitrogen, which can be possible indicators of kidney problems

Angioedema is a rare side effect of ACE inhibitors. A person may experience swelling of the face, lips, and upper airway. It can be a life threatening side effect.

ACE inhibitors are not suitable for people who are pregnant or have a history of angioedema.

Additionally, a person should not take ACE inhibitors alongside a drug called aliskiren, which treats high blood pressure.

ARBs offer an alternative for people who cannot tolerate ACE inhibitors.

ARBs widen blood vessels to allow easier blood flow. They can reduce the risk of:

  • death from a cardiac issue
  • stroke
  • heart attack

ARB medication is also a vasodilator that affects angiotensin. ARBs prevents angiotensin ll from interacting with its receptors, which transmit the signals to constrict blood vessels.


ARBs come in tablet form in varying doses. It is available in combination with other medications if necessary.

A doctor can recommend which medication to try and the starting dosage.

Some options include:

Initial daily dosageTarget dosage
candesartan (Atacand)4–8 mg, once daily32 mg, once daily
losartan (Cozaar)25–50 mg, once daily50–150 mg, once daily
valsartan (Diovan)20–40 mg, twice daily160 mg, twice daily

Side effects and considerations

Certain people should not take ARBs. They include people who:

  • have high potassium levels
  • have low blood pressure
  • are pregnant

Otherwise, ARBs have a low chance of side effects. In rare instances, a person may experience:

  • cough
  • rash
  • anaphylaxis
  • blood vessel inflammation
  • low white blood cells
  • abnormal liver tests

ARNI medication is a combination of an ARB and a neprilysin inhibitor. ARNIs relax blood vessels to decrease heart rate and blood pressure.

A 2014 trial found that ARNI medication is better than ACE inhibitors or ARBs at decreasing the chance of heart failure after a heart attack.

Healthcare professionals may switch an ACE inhibitor or ARB for an ARNI medication if the person has chronic symptomatic HFrEF, provided they tolerate ACE inhibitors or ARBs.

Before starting an ARNI medication, a person should stop taking ACE inhibitor medication and wait at least 36 hours.


Sacubitril/valsartan (Entresto) is the ARNI doctors prescribe for heart failure. It is available as an oral tablet.

Sacubitril/valsartan (Entresto) comes in three strengths:

Tablet doseSacubitril portionValsartan portion
50 mg24 mg26 mg
100 mg49 mg51 mg
200 mg97 mg103 mg

Dosing depends on the person’s status:

Person’s statusDosage range
no previous ACE inhibitors or ARBs50–200 mg, twice daily
previous low dose ACE inhibitors or ARBs50–200 mg, twice daily
previous moderate to high ACE inhibitors or ARBs100–200 mg, twice daily

Side effects and considerations

ARNI medication side effects include:

  • nausea
  • headache
  • diarrhea
  • vomiting
  • itching
  • skin rash

A person should seek prompt medical care if they experience:

  • severe headache or chest pain
  • shortness of breath
  • allergy symptoms, such as swelling of the tongue, lips, or mouth

People who may not be able to use ARNI medication include those who:

  • have liver impairment
  • are pregnant
  • are breastfeeding or chestfeeding

It is also worth noting that Ernesto does not have a generic form, so it may be more expensive than an ACE inhibitor or ARB.

Beta-blockers stop the effects of epinephrine, the hormone also known as adrenaline. They also prevent the kidneys from producing angiotensin ll.

Beta-blockers slow heart rate, relax the heart muscle, and reduce blood pressure.


Doctors commonly prescribe beta-blockers as oral medication in tablet form. They are also available intravenously and as an injectable.

Beta-blocker dosages can vary. Examples include:

Initial daily dosageTarget dosage
metoprolol succinate (Toprol-XL)12.5–25 mg, once daily200 mg, once daily
carvedilol (Coreg)3.125 mg, twice daily25–50 mg, twice daily
carvedilol (Coreg CR)10 mg, once daily80 mg, once daily
bisoprolol1.25 mg, once daily10 mg, once daily

Side effects

Beta-blockers have some side effects, which may include:

  • fatigue
  • lightheadedness
  • dizziness
  • reduced blood supply to hands and feet
  • sleep disruption
  • nausea
  • erectile dysfunction

More serious side effects include:

  • shortness of breath
  • cough worsened by exercise
  • irregular heart rate
  • leg and ankle swelling
  • chest tightening
  • wheezing
  • yellowish skin
  • yellow whites of eyes

Diuretics make it easier for the heart to pump blood. They cause the kidneys to produce more urine, which helps flush excess water and salt out of the body.

Diuretics can:

  • reduce the heart’s workload
  • lower blood pressure
  • ease shortness of breath
  • lessen bloating and swelling
  • increase urination frequency

People usually take diuretics orally. If a person has advanced heart failure, they can receive this medication intravenously in a hospital.

There are different categories of diuretics, including:

  • loop
  • thiazide
  • potassium-sparing
  • carbonic anhydrase inhibitors


The recommended dose for treating heart failure depends on the type of diuretic:

Loop diuretics

The following table outlines the dose options for loop diuretics:

Dose rangeDaily maximum
furosemide (Lasix)40–240 mg600 mg
torsemide (Demadex)5–20 mg200 mg
bumetanide (Bumex)1–5 mg10 mg
ethacrynic acid (Edecrin)25–100 mg200 mg

Thiazide-type diuretics

The following table outlines the dose options for thiazide-type diuretics:

Dose rangeDaily maximum
hydrochlorothiazide (Esidrix)12.5–100 mg200 mg
chlorothiazide (Diuril)250–500 mg1,000 mg

Thiazide-like diuretics

The following table outlines the dose options for thiazide-like diuretics:

Dose rangeDaily maximum
chlorthalidone (Thalitone)12.5–25 mg100 mg
metolazone (Mykrox)2.5–10 mg20 mg
indapamide (Lozol)2.5–5 mg5 mg

Potassium-sparing diuretics

The following table outlines the dose options for potassium-sparing diuretics:

Dose rangeDaily maximum
amiloride (Midamor)5–20 mg20 mg
triamterene (Dyrenium)100–200 mg200 mg
spironolactone (Aldactone)12.5–50 mg200 mg
eplerenone (Inspra)50–200 mg200 mg

Carbonic anhydrase inhibitors

The following table outlines the dose options for carbonic anhydrase inhibitors:

Dose rangeDaily maximum
acetazolamide – oral (Diamox)250–375 mg500 mg
acetazolamide – IV500 mg500 mg

Side effects

Prescription diuretics may have side effects that include:

  • low fluid volume
  • dizziness
  • fainting
  • headache
  • thirst
  • muscle cramps
  • dehydration
  • fatigue
  • weakness
  • skin rash
  • frequent urination
  • nausea
  • vomiting
  • constipation
  • mineral deficiencies after long-term use

HCN channels are also called pacemaker channels because they control the heart’s rhythm. HCN channel blockers slow heart rate, making it easier for the heart to pump more blood with each beat.

Ivabradine (Corlanor) was the first HCN channel blocker medication approved to treat heart failure. It is taken orally.

A 2016 review notes that in the SHIFT clinical trial, ivabradine reduced the risks associated with heart failure by 18% relative to placebo.


The starting dosage of ivabradine is 2.5–5 mg twice daily. It is adjusted as required after 2 weeks from the start of use. The maximum dosage is 7.5 mg twice daily.

Side effects

Ivabradine may have side effects, including:

  • pulse that is too slow
  • high blood pressure
  • atrial fibrillation
  • vision changes

Doctors may also prescribe other medications to treat heart failure, such as:

  • Digoxin: This is a drug classified as a cardiac glycoside. It can help decrease hospitalization but does not reduce the risk of death.
  • Vericiguat (Verquvo): This is a newer drug to treat heart failure. It is classified as a guanylyl cyclase stimulator. It may decrease the likelihood of death and hospitalization in people with heart failure.

Medication for systolic heart failure can make it easier for the heart to circulate blood. These medications can help widen blood vessels, reduce fluid and sodium volume, and increase the heart’s ability to pump.

First-line heart failure medications include beta-blockers and ACE inhibitors, but a doctor may also prescribe other options.