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Drug Treatment for Heart Failure

By

Jonathan G. Howlett

, MD, Libin Cardiovascular Institute of Alberta

Last full review/revision Apr 2020| Content last modified Apr 2020
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NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version
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Heart failure is a disorder in which the heart is unable to keep up with the demands of the body, leading to reduced blood flow, back-up (congestion) of blood in the veins and lungs, and/or other changes that may further weaken or stiffen the heart. Drug treatment of heart failure involves

  • Drugs to help relieve symptoms: Diuretics, vasodilators, or digoxin

  • Drugs to help improve survival: Angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, aldosterone antagonists, angiotensin II receptor blockers (ARBs), angiotensin receptor/neprilysin inhibitors (ARNIs), sodium-glucose co-transporter 2 inhibitors, or sinus node inhibitors

The type of drug used depends on the type of heart failure. In systolic heart failure (heart failure with reduced ejection fraction, HFrEF), all drug classes helpful. In diastolic heart failure (heart failure with preserved ejection fraction, HFpEF), only ACE inhibitors, ARBs, aldosterone antagonists, and beta-blockers are typically used. In heart failure with mid-range ejection fraction, ARNIs may be helpful.

It is important for people to take their drugs regularly and be sure not to let the prescription run out.

Aldosterone antagonists

Aldosterone is a hormone that causes the kidneys to retain salt and water. Thus, aldosterone antagonists (blockers) directly block the effects of aldosterone (unlike ACE inhibitors which block it indirectly) and help limit fluid retention. These drugs improve survival and reduce hospitalization in people with heart failure.

Angiotensin-converting enzyme (ACE) inhibitors

Angiotensin II is a hormone that triggers release of aldosterone and vasopressin, both of which cause the kidneys to retain salt and water. ACE inhibitors thus help limit fluid retention and are one of the mainstays of systolic heart failure treatment. These drugs not only reduce symptoms and the need for hospitalization but also prolong life. ACE inhibitors reduce blood levels of the hormones angiotensin II and thus aldosterone, which normally help increase blood pressure (see figure Regulating Blood Pressure: The Renin-Angiotensin-Aldosterone System). By doing so, ACE inhibitors cause arteries and veins to widen (dilate) and help the kidneys excrete excess water, thus decreasing the amount of work the heart has to do. These drugs also may have direct beneficial effects on the heart and blood vessel walls.

Angiotensin II receptor blockers (ARBs)

Angiotensin II receptor blockers (ARBs) have effects similar to those of ACE inhibitors. ARBs are used instead of ACE inhibitors in some people who cannot tolerate ACE inhibitors because of cough, which is a side effect of ACE inhibitors that is less likely with ARBs.

Angiotensin receptor/neprilysin inhibitors

Angiotensin receptor/neprilysin inhibitors (ARNIs) are a newer combination drug for the treatment of heart failure. They include an ARB and a new class of drug, neprilysin inhibitors. Neprilysin is an enzyme involved in the breakdown of certain substances (peptides) that signal the body to excrete sodium. By inhibiting the breakdown of these peptides, these drugs lower blood pressure and increase sodium excretion, lowering the heart's workload. The drugs prolong life better than ACE inhibitors or ARBs alone in people with systolic heart failure.

Beta-blockers

Beta-blockers are often used with ACE inhibitors to treat heart failure and are another mainstay of heart failure treatment. These drugs block the action of the hormone norepinephrine (which increases stress on the heart) and produce long-term improvement in heart function and survival and are an essential treatment in people with systolic heart failure. Beta-blockers may reduce the force of the heart’s contractions initially, so they are usually introduced after heart failure has first been stabilized with other drugs.

Digoxin

Digoxin, one of the oldest treatments for heart failure, increases the force of each heartbeat and slows a heart rate that is too rapid. Digoxin helps relieve symptoms for some people with systolic heart failure but, unlike other heart failure drugs discussed here, it does not prolong life.

Diuretics

Diuretics ("water pills") are often prescribed when salt restriction alone does not reduce fluid retention. These drugs help the kidneys eliminate salt and water by increasing urine formation and thus decreasing fluid volume throughout the body.

Loop diuretics, such as furosemide or bumetanide, are the diuretics most commonly used for heart failure. These diuretics are usually taken by mouth on a long-term basis, but in an emergency, they are very effective when given intravenously. Loop diuretics are preferred for moderate to severe heart failure.

Thiazide diuretics, such as hydrochlorothiazide, which have milder effects and can lower blood pressure, may be prescribed particularly for people who also have high blood pressure.

Loop and thiazide diuretics can cause potassium to be lost in the urine, resulting in hypokalemia. Consequently, a diuretic that causes potassium levels to increase (a potassium-sparing diuretic) or a potassium supplement may be given as well. For all people with heart failure, spironolactone is the preferred potassium-sparing diuretic and can be used unless kidney function is severely reduced. It can prolong life in people with heart failure.

Taking diuretics can worsen urinary incontinence. However, a dose of a diuretic can usually be timed so that the risk of incontinence does not occur when a bathroom is unavailable or when access to one is inconvenient.

Sinus node inhibitors

The sinus node is the part of the heart that triggers the beat and sets the heart rate. Ivabradine is the first drug in this class of drugs that slow down the rate of the sinus node. Slowing the heart reduces the workload of the heart and can help reduce how often certain people with heart failure need to be hospitalized.

Sodium glucose co-transporter 2 inhibitors

Sodium glucose co-transporter 2 inhibitors are used in the treatment of diabetes. In addition to lowering the blood sugar (glucose) level in the blood, they also have beneficial effects on the heart muscle and blood vessels. One drug in this class, dapagliflozin has been shown to decrease heart failure symptoms and improve quality of life in some people with heart failure.

Vasodilators

Vasodilators (drugs that widen blood vessels) make it easier for the heart to pump blood. These drugs, such as hydralazine, isosorbide dinitrate, and nitroglycerin patches or spray, are not used as often as ACE inhibitors or angiotensin II receptor blockers, which are more effective. Nonetheless, people who do not respond to or cannot take ACE inhibitors or angiotensin II receptor blockers can benefit from vasodilators. In a few people with advanced symptoms, these drugs may improve quality and quantity of life when added to ACE inhibitors or angiotensin inhibitors.

Other drugs used for heart failure

Other drugs are sometimes helpful.

Anticoagulants, such as warfarin, may be given to prevent clots from forming in the heart chambers.

If the heart rhythm is abnormal, antiarrhythmic drugs (see table Some Drugs Used to Treat Arrhythmias) may be given.

Doctors have tried using drugs besides digoxin that increase the heart's pumping power, but thus far, none have proved helpful and some increase risk of death.

Table
icon

Some Drugs Used to Treat Heart Failure

Drug*

Comments†

Aldosterone antagonists

Eplerenone

Spironolactone

These drugs block the action of the hormone aldosterone, which promotes salt and fluid retention and may have direct adverse effects on the heart.

Both are potassium-sparing diuretics and improve survival and reduce hospitalizations.

Eplerenone is less likely than spironolactone to cause breast tenderness or enlargement in men.

Angiotensin-converting enzyme (ACE) inhibitors

Captopril

Enalapril

Lisinopril

Perindopril

Quinapril

Ramipril

Trandolapril

ACE inhibitors cause blood vessels to widen (dilate), thus decreasing the amount of work the heart has to do.

They may also have direct beneficial effects on the heart.

These drugs are the mainstay of heart failure treatment.

They reduce symptoms and the need for hospitalization, and they prolong life.

Angiotensin II receptor blockers

Candesartan

Losartan

Valsartan

Angiotensin II receptor blockers have effects similar to those of ACE inhibitors and may be tolerated better.

They may be used in people who cannot take an ACE inhibitor.

Angiotensin receptor/neprilysin inhibitor

Valsartan plus sacubitril

The combination drug may be given to people who have systolic heart failure with mild or moderate symptoms. In these people, this combination drug prolongs life better than an ACE inhibitor used alone.

People should stop taking ACE inhibitors at least 36 hours before starting valsartan/sacubitril.

Beta-blockers

Bisoprolol

Carvedilol

Metoprolol

Beta-blockers slow the heart rate and block excessive stimulation of the heart.

These drugs are usually used with ACE inhibitors and provide an added benefit.

They may temporarily worsen symptoms but result in long-term improvement in heart function.

Cardiac glycoside

Digoxin

Cardiac glycosides, such as digoxin, increase the force of each heartbeat and slow the heart rate in people with atrial fibrillation.

Loop diuretics

Bumetanide

Ethacrynic acid

Furosemide

Torsemide

These diuretics help the kidneys eliminate salt and water, thus decreasing the volume of fluid in the bloodstream.

Potassium-sparing diuretics

Amiloride

Triamterene

Because these diuretics prevent potassium loss, they may be given in addition to thiazide or loop diuretics, which cause potassium to be lost.

Spironolactone and eplerenone are potassium-sparing diuretics that are also aldosterone receptor blockers.

Sinus node inhibitors

Ivabradine

Ivabradine may be used in certain people who have systolic heart failure.

Sodium glucose co-transporter 2 inhibitors

These drugs for diabetes also have beneficial effects in heart failure whether or not people have diabetes

Dapagliflozin

Typically are not be used in people who have low blood pressure or poor kidney function

Thiazide and thiazide-like diuretics

Chlorthalidone

Hydrochlorothiazide

Indapamide

Metolazone

The effects of these diuretics are similar to loop diuretics. The two types of diuretics are particularly effective when used together.

Opioids

Morphine

Morphine may be given to relieve anxiety in a medical emergency, such as acute pulmonary edema.

Careful supervision is necessary.

O Vasodilators

Hydralazine

Isosorbide dinitrate

Nitroglycerin

Vasodilators cause blood vessels to dilate.

These vasodilators are usually given to people who cannot take an ACE inhibitor or angiotensin II receptor blocker.

Nitroglycerin is particularly useful for people who have heart failure and angina and for those who have acute heart failure

The combination of hydralazine and nitrates has been shown to be effective, particularly in blacks.

* These specific drugs have been better studied to prevent or treat heart failure.

† Selected side effects for ACE inhibitors, angiotensin II receptor blockers, diuretics, and beta-blockers are listed in the table (see Table: Antihypertensive Drugs).

NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version
Click here for the Professional Version
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