How ACE Inhibitors Effectively Treat Heart Failure

Heart x-ray concept
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Using an angiotensin-converting enzyme (ACE) inhibitor drug is an important part of treating heart failure. In people with heart failure, ACE inhibitors have been shown to reduce the need for hospitalization, improve symptoms, and even prolong survival. If you have been diagnosed with congestive heart failure, you should be treated with an ACE inhibitor unless your doctor has a very good reason not to do so.

What Do ACE Inhibitors Do?

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

When blood flow to the kidneys is reduced, 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, and (by stimulating the release of the hormone aldosterone from the adrenal glands) causes the body to retain sodium.

The RAAS tends to work overtime in people with heart failure, which increases sodium retention and blood pressure, and causes 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.

By this means, ACE inhibitors reduce the stress on the heart and allow the weakened heart muscle to pump more efficiently.

ACE inhibitors are also very useful in the treatment of hypertension, and they have been shown to improve outcomes in people who have had heart attacks. In addition, they can help prevent kidney damage in people with diabetes.

ACE Inhibitors in Heart Failure

Several major clinical trials have looked at the use of ACE inhibitors in people with heart failure. All of them showed significant benefit. A meta-analysis of five such trials that included over 12,000 people with heart failure showed that ACE inhibitors significantly reduced the need for hospitalization, improved survival, and lowered the risk of heart attacks. Symptoms of heart failure such as dyspnea (shortness of breath) and fatigue were also improved.

Current guidelines from the American College of Cardiology and American Heart Association strongly recommend that ACE inhibitors be given to anyone who has heart failure, and in addition, to anyone who has a reduced left ventricular ejection fraction (less than 0.4) whether or not they have had actual heart failure.

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 captopril (Capoten), enalapril (Vasotec), lisinopril (Zestril), ramipril (Altace), and trandolarpril (Mavik).

When first prescribed, ACE inhibitors are usually started at a low dose, and the dosage is gradually increased to the higher doses used in the clinical trials.

Gradually increasing the dosage helps prevent adverse effects. If the targeted 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 the the higher doses are preferred because they have been formally tested in clinical studies.

ACE inhibitors and race. Some studies suggest that ACE inhibitors may be less effective in black people than in whites, but the evidence is conflicting. Current guidelines recommend using ACE inhibitors everyone with heart failure, regardless of race.

 

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

Adverse Effects of ACE Inhibitors

While ACE inhibitors are usually tolerated quite well, certain side effects may occur.

ACE inhibitors may reduce the blood pressure too much, producing symptoms of weakness, dizziness, or syncope. This problem can usually be avoided by starting with a low dose and gradually building up to higher doses.

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.

ACE inhibitors can increase blood potassium levels. While this effect is usually very modest and not medically significant. However, in some people (about 3%) potassium levels can become too high.

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 quite disturbing and usually requires discontinuation of the drug.

Very rarely, people taking ACE inhibitors can experience angioedema—a severe allergic-like reaction that can become quite dangerous.

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. In addition, ARBs are roughly as effective as ACE inhibitors in the treatment of hypertension. Commonly used ARB drugs include candesartan (Atacand), lasartan (Cozaar), and valsartan (Diovan). Several other ARB drugs are available as well.

The Bottom Line

If you have heart failure, to minimize your symptoms and to optimize your outcome, you should be prescribed an ACE inhibitor unless there is a very good reason not to.

Sources:

Flather MD, Yusuf S, Køber L, et al. Long-Term ACE-inhibitor Therapy in Patients With Heart Failure or Left-Ventricular Dysfunction: a Systematic Overview of Data From Individual Patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000; 355:1575.

McMurray JJ, Adamopoulos S, Anker SD, et al. ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012; 33:1787.

Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Fuideline for the Management of Heart Failure: a Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 62:e147.

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