How ACE Inhibitors Treat Heart Failure

By Richard N. Fogoros, MD

Medically reviewed by Jeffrey S. Lander, MD

Using an angiotensin-converting enzyme (ACE) inhibitor drug is an important part of treating heart failure. In people with this condition, ACE inhibitors have been shown to improve symptoms, reduce the need for hospitalization, and even prolong survival.

If you have been diagnosed with heart failure, you may be treated with an ACE inhibitor.

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How ACE Inhibitors Work

ACE inhibitors block a key enzyme in the renin-angiotensin-aldosterone system (RAAS). The RAAS is a chain of enzymes that work together to regulate blood pressure and the concentration of sodium in the blood.¹

When blood flow to the kidneys is reduced—a common occurrence in heart failure, in which the heart isn't able to pump enough blood to meet the body's needs—an enzyme called renin is released into the bloodstream. Renin causes another enzyme, angiotensin I, to increase.

Angiotensin I is converted by ACE into angiotensin II. Angiotensin II increases blood pressure by causing blood vessels to constrict. Angiotensin II also stimulates the release of the hormone aldosterone, which causes the body to retain sodium. This makes the body retain more water and increases blood volume.

The RAAS tends to work overtime in people with heart failure. By increasing blood pressure and blood volume, it forces the heart to work harder than it should.

ACE inhibitors work by blocking the formation of angiotensin II. In people with heart failure, this lowers blood pressure and reduces sodium retention. In this way, ACE inhibitors relieve the stress on the heart and allow the weakened heart muscle to pump more efficiently.²

ACE inhibitors are one of the first-line treatments for hypertension (high blood pressure),³ and they have been shown to improve outcomes in people who have had heart attacks.⁴ In addition, they can help prevent kidney damage in people with diabetes.⁵

Effectiveness in Heart Failure

Several major clinical trials have looked at the use of ACE inhibitors in heart failure treatment. They have shown that ACE inhibitors significantly reduce the need for hospitalization, improve survival, and lower the risk of heart attacks. Symptoms of heart failure such as dyspnea (shortness of breath) and fatigue also improve.⁶

Current guidelines from the American College of Cardiology (ACC) and the American Heart Association (AHA) strongly recommend a renin-angiotensin system blocker for those with heart failure with a reduced left ventricular ejection fraction (less than 40%). ACE inhibitors are one of three recommended first-line therapy options.⁷

Other treatment options include angiotensin-receptor neprilysin inhibitors (ARNIs) and angiotensin II receptor blockers (ARBs).

The ACC and AHA now recommend the use of ARNIs (a newer type of medication) over ACE inhibitors in those with mild to moderate heart failure symptoms. However, ACE inhibitors may still be preferred in certain cases.⁷

ACE Inhibitor Drug Names

Several ACE inhibitors are on the market, and it is generally thought that they are equally beneficial in the treatment of heart failure. Commonly used ACE inhibitors include:

Accupril (quinapril)
Altace (ramipril)
Capoten (captopril)
Mavik (trandalopril)
Monopril (fosinopril)
Vasotec (enalapril)
Zestril (lisinopril)

When first prescribed, ACE inhibitors usually are started at a low dose, and the dosage is gradually increased to the target dosage. Gradually increasing the dosage helps prevent adverse effects. If the higher doses are not tolerated well, treatment is usually continued at a lower, better-tolerated dose.

Most experts believe that lower doses of ACE inhibitors are nearly as effective as higher doses, but higher doses are preferred because they have been formally tested in clinical studies.

Groups with Reduced Benefit

Some studies suggest that ACE inhibitors may be less effective in Black people than in Whites, but the evidence is conflicting. For Black people with certain types of heart failure plus hypertension, other medications may be recommended instead of ACE inhibitors.⁸

Clinical studies have not proven the same magnitude of benefit with ACE inhibitors in females as has been demonstrated in males. However, the preponderance of evidence still favors using ACE inhibitors in all females with heart failure.⁹

Side Effects of ACE Inhibitors

While ACE inhibitors are usually tolerated quite well, certain side effects may occur, including:¹

Cough: The most prominent side effect of ACE inhibitors is a dry, hacking cough, which may be seen in up to 20% of people given these drugs. While not a dangerous problem, this side effect can be bothersome and usually requires discontinuation of the drug.
Hypotension (low blood pressure): ACE inhibitors may reduce blood pressure too much, producing symptoms of weakness, dizziness, or syncope (temporary loss of consciousness). This problem can usually be avoided by starting with a low dose and gradually building up to higher doses.
Impaired kidney function: Especially in people who have underlying kidney disease, the use of ACE inhibitors can further reduce kidney function. For this reason, kidney function (blood tests) should be monitored in people who have kidney disease and are beginning ACE inhibitors.
High blood potassium (hyperkalemia): ACE inhibitors can increase blood potassium levels. While this effect is usually very modest and not medically significant, in about 3% of people, potassium levels can become too high.
Angioedema: Very rarely, people taking ACE inhibitors can experience angioedema, a severe allergic-like reaction that can become quite dangerous.

Precautions and Contraindications

People who are pregnant, breastfeeding, or planning to become pregnant should not take ACE inhibitors, because the drugs can cause serious problems in the baby. Complications can include problems with kidney function, skull formation, and even death. People should stop taking ACE inhibitors as soon as they learn they are pregnant.²

Some other reasons people should not take ACE inhibitors include:¹

History of angioedema
Low blood pressure
Aortic stenosis (narrowing of the aortic valve opening)
Severe hyperkalemia
Dehydration/low blood volume
Renovascular hypertension (high blood pressure due to the narrowing of the arteries that carry blood to your kidneys)

In addition, people taking an ACE inhibitor should avoid using nonsteroidal anti-inflammatory drugs (NSAIDs), such as Advil (ibuprofen) or Aleve (naproxen), as these pain relievers may make the ACE inhibitor less effective and increase the risk of kidney damage.

ARBs as a Substitute for ACE Inhibitors

Angiotensin II receptor blockers (ARB drugs) are similar to ACE inhibitors in that they interrupt the RAAS cascade and reduce the effect of the angiotensin II enzyme. Because ARBs only infrequently cause cough and angioedema, they are sometimes used as a substitute in people who have had these adverse effects with ACE inhibitors.

ARBs have been shown to be effective in the treatment of heart failure, though to a lesser extent than ACE inhibitors.¹⁰ In addition, ARBs are roughly as effective as ACE inhibitors in the treatment of hypertension.¹¹

Commonly used ARB drugs include: