Angiotensin converting enzyme (ACE) inhibitors are a class of medications used to treat high blood pressure and heart failure. They can also slow the progression of kidney disease in women with diabetes. ACE inhibitors dilate (widen) blood vessels and increase the amount of water your kidneys get rid of, lowering blood pressure.
Angiotensin Converting Enzyme (ACE) Inhibitors
|How it is given:||Oral (tablet or capsule), intravenous (IV)|
|What it is used for:||
|You should not be treated with it if:||
|Pregnancy/nursing:||ACE inhibitors should not be used during pregnancy. Captopril, enalapril, and quinapril (except early postpartum) are probably safe during nursing, but be sure to discuss the possible risks and benefits with your doctor. The safey of ramipril, lisinopril, and fosinopril during nursing are unknown and may be harmful.|
What are they used for?
In women with heart failure, ACE inhibitors help relieve the symptoms of heart failure, slow the progression of the disease, and improve survival. They are one of the first medications used in the treatment of women with systolic heart failure, whether or not they have started experiencing symptoms.1 By reducing the heart's workload, ACE inhibitors can decrease leg swelling, relieve shortness of breath, improve your ability to perform daily tasks, minimize the time you spend in the hospital, and help you live longer.
ACE inhibitors are not as effective in African Americans as in whites. Click here for more.
Who should receive ACE inhibitors to prevent or treat heart failure?
You should receive ACE inhibitors if you:1
- Are at high risk of developing heart failure (especially if you have a history of coronary artery disease or heart attack, diabetes or high blood pressure)
- Have structural changes in your heart (enlarged ventricles or decreased ejection fraction) but do not yet have heart failure symptoms
- Have symptoms caused by systolic heart failure (blood pumping problems)
For women in the early stages of heart failure who do not yet have symptoms, ACE inhibitors can help prevent the disease from getting worse and delay the onset of symptoms.2,3 They accomplish this by slowing changes in the heart's structure that will eventually make heart failure worse.4,5
For women who have systolic heart failure (mild to severe), ACE inhibitors improve symptoms such as fatigure and shortness of breath, improving your ability to perform daily tasks (measured by NYHA functional class).6-11 The also make you less likely to be hospitalized and improve survival.3,12,13 In one study with 6800 patients (14% were women), the addition of an ACE inhibitor increased life expectancy by more than 9 months but the benefit in women remained unclear because so few women were enrolled.14 Women taking an ACE inhibitor also need fewer additional heart failure medications compared to those not taking ACE inhibitors.
Some women with heart failure symptoms caused by diastolic heart failure (blood pumping problems) may also benefit from ACE inhibitors, but the benefits are not as clear in these patients. While a few studies have found that these women have better heart function and lower death rates when they receive ACE inhibitors, more research is needed to determine exactly what kinds of patients benefit from the treatment.15,16
Who should NOT receive ACE inhibitors?
Women who are pregnant or nursing should not receive ACE inhibitors because of risks to the fetus and baby.1 ACE inhibitors should be used carefully in women with kidney problems or very low systolic blood pressures.1 You should not take them if you have experienced an allergy like swellong of the face, lips, mouth or throat (angioedema) or kidney failure without urine production (anuric renal failure) while taking ACE inhibitors.
ACE inhibitors are not as effective in African Americans as in whites; this does not mean that African Americans should not receive ACE inhibitors, only that additional medications may be necessary. Click here for more.
How do ACE inhibitors work?
When the heart is unable to pump blood efficiently, as in heart failure, there is less blood flow to the kidneys. This activates a complex hormone system that triggers blood vessel constriction, signals the kidneys to hold on to more water (increasing the total volume of blood in your vessels), and raises your blood pressure. At first, these changes help compensate for the heart's weak pumping ability and allow more blood to reach other organs. However, as heart failure progresses, these changes become harmful and contribute to a further decline of the heart function.
ACE inhibitors counteract these early changes, stopping the signals to constrict blood vessels and retain water. They also increase blood vessel dilation by preventing the breakdown of a molecule that widens blood vessels, keeping it active for longer. When blood vessels are widened, the heart does not have to work as hard to pump blood to the rest of the body. Imagine trying to squeeze a bottle of water through a wide straw instead of a skinny straw. ACE inhibitors can also improve the heart muscle's ability to relax when the heart expands to fill with blood ( diastole), enabling the heart to pump out more blood with each heartbeat.
Do ACE inhibitors work as well in women as in men?
ACE inhibitors are a part of the standard initial treatment regiment in both women and men with heart failure. Studies so far suggest that women benefit from ACE inhibitor therapy, but in most major trials of the drug only 20% to 30% of participants were women.3,11 As a result, information on ACE inhibitors' specific benefits in women is limited. Until more definitive data are available, it is recommended that women with heart failure receive ACE inhibitor therapy.1
One study that combined data from 12 major trials found that men receiving ACE inhibitors had improved survival, while women had a trend towards improved outcomes. However, there were too few women in the studies to be sure this wasn't due to chance.17 Other analyses have found ACE inhibitors reduce the need for hospitalization and improve survival to a similar degree in women and men.18,19 In one recent randomized trial, women experienced lower death rates when treated with ACE inhibitors (11.3% in women vs. 14.9% in men).20 A recent large study of patients with any type of heart failure found demonstrated that both women and men with heart failure experienced a significant decrease in mortality when they received ACE inhibitors. However, men did have a greater risk reduction than women.21
Are women missing out on ACE inhibitor therapy?
Despite being a first-choice therapy in heart failure, some studies in the past have suggested that women with heart failure receive ACE inhibitors less often than men.22-25 However, the National Heart Failure project, which studied more than 17,000 Medicare patients hospitalized for heart failure, found no significant difference in ACE inhibitor prescription rates between women and men, with about 68% of all patients receiving them.26,27
African-Americans do not respond as well as whites to ACE inhibitors as a standalone medication to control high blood pressure. The drug is less likely to work at all (in one trial, only 20% of African Americans responded to the drug compared with 55% of whites), and even when it does work it does not lower blood pressure as much in African Americans.28,29 However, when ACE inhibitors are being used to treat heart failure, the racial differences are not as clear.
In one ACE inhibitor study in patients with heart failure and no symptoms, whites receiving the drug had a lower incidence of first heart failure hospitalization, a benefit that was not seen in African Americans. However, African Americans taking ACE inhibitors had improved symptoms and survival similar to their white counterparts.30,31
Current recommendations are that African Americans should receive ACE inhibitors as part of the standard heart failure treatment (unless have side effects that make them unable to tolerate the drug).SUP>1 In addition, they may also benefit from other medications like hydralazine and isosorbide dinitrate which can reduce the strain on the heart and improve survival.32
What are the side effects of ACE inhibitors?
Cough is the most common side effect of ACE inhibitors, occurring in 5% to 20% of patients. It is more common in women than in men.33 In most cases, treatment with ACE inhibitors does not have to be stopped, but patients may wish to switch to another medication if the cough is severe. The cough disappears when a patient stops taking the drug. Women may be more likely than men to experience side effects of ACE inhibitor medications (in one study, 26% of women compared with 21% of men).34,35
When first starting ACE inhibitors, a women may experience a drop in blood pressure, which can occasionally cause dizziness, especially when changing posture such as standing up. This is more common in women who are also taking diuretics, and can usually be controlled by adjusting the types or doses of blood pressure medications and does not usually requiring stopping ACE inhibitors.
One potentially dangerous (but rare) side effects is swelling of the lips and throat caused by fluid buildup underneath the deep layers of skin (angioedema). This is more common in African Americans, but is still rare. Other side effects may include decreased kidney function and increased potassium levels, which may require switching to a different type of medication.
Are there special concerns about ACE inhibitors in women with lung disease?
Telling the difference between the dry cough that is a common side effect of ACE inhibitors and a cough caused by another condition can be difficult, particularly in women with lung disease such as asthma or chronic obstructive pulmonary disease (COPD). It is important to diagnose the cause of a cough in patients taking ACE inhibitors to avoid stopping ACE treatment unnecessarily.
If you develop a dry, nonproductive cough while taking ACE inhibitors, your doctor will examine you closely to determine if lung disease or respiratory infection could be the cause. If she or he believes it is related to the medication, you may be asked to stop taking the ACE inhibitor for a brief period and then start taking it again. If the cough goes away after you stop taking the drug and comes back when you start again, it is very likely the medication was responsible for your symptoms. If this is the case, you and your doctor will decide whether you want to try living with the side effects of the drug or switch to an alternate treatment.
If I cannot take an ACE inhibitor, what are some alternatives?
ACE-inhibitors are the first choice medicine because they are the most-studied drug in their class and work in multiple ways. Alternatives to ACE inhibitors depend on why you are unable to tolerate the medication. Patients who experience side effects like cough may be better off taking an angiotensin II receptor blocker (ARB). Those that develop swelling of the lips and tongue (angioedema) will need discuss their options with their physician since they may have a similar reaction to an ARB.1,36,37 ARBs appear to work about as well as ACE inhibitors for heart failure treatment and result in better outcomes for people who can't take ACE inhibitors.36,38,39
If side effects like low blood pressure, high potassium levels, or kidney problems are forcing someone to stop taking ACE inhibitors, the same problems would likely occur after switching to an ARB. In these patients, different types of medication (such as nitrates) can be used to dilate blood vessels.
My doctor has prescribed ACE inhibitors. What should I watch out for?
While taking an ACE inhibitor, it is important to follow the doses prescribed to you closely. When first starting the medication, your physician may start you on a lower dosage to minimize the low blood pressure side effects. Afterwards, the dosages maybe increased and adjusted by a physician to manage your blood pressure and symptoms while minimizing any side effects.
If you experience swelling of your lips, tongue, or throat, get medical attention immediately. This may be accompanied by nausea, vomiting, or diarrhea. These are signs of a rare but potentially deadly side effect of ACE inhibitors called angioedema that requires immediate treatment. This side effect occurs in only about 2 of every 1000 people treated with ACE inhibitors, but is more common in African Americans and women.40
If you experience dizziness when sitting up or standing up quickly, this may be a sign that your medication is causing low blood pressure. Talk to you doctor about adjusting your dose or medication to minimize this side effect.
A persistent, dry cough or itching in the throat is one of the most common side effects of ACE inhibitors. Discuss this with your doctor before stopping your medication because other causes of coughing (including worsening heart failure symptoms from increased fluid in your lungs) need to be considered.
ACE inhibitors can interact with some other medications, including NSAIDS such as aspirin, certain muscle relaxants, and drugs used to treat gout. Talk to your doctor before taking aspirin (which may make the ACE inhibitor less effective) or potassium-sparing diuretics to make sure. For more details, see Medications to Avoid.
- Hunt SA. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. September 20, 2005 2005;46(6):e1-82.
- Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigattors. N Engl J Med. Sep 3 1992;327(10):685-691.
- Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med. Sep 3 1992;327(10):669-677.
- Pouleur HG, Konstam MA, Udelson JE, Rousseau MF. Changes in ventricular volume, wall thickness and wall stress during progression of left ventricular dysfunction. The SOLVD Investigators. J Am Coll Cardiol. Oct 1993;22(4 Suppl A):43A-48A.
- Sabbah HN, Shimoyama H, Kono T, et al. Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction. Circulation. Jun 1994;89(6):2852-2859.
- Sharpe DN, Murphy J, Coxon R, Hannan SF. Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study. Circulation. Aug 1984;70(2):271-278.
- Cleland JG, Dargie HJ, Ball SG, et al. Effects of enalapril in heart failure: a double blind study of effects on exercise performance, renal function, hormones, and metabolic state. Br Heart J. Sep 1985;54(3):305-312.
- Erhardt L, MacLean A, Ilgenfritz J, Gelperin K, Blumenthal M. Fosinopril attenuates clinical deterioration and improves exercise tolerance in patients with heart failure. Fosinopril Efficacy/Safety Trial (FEST) Study Group. Eur Heart J. Dec 1995;16(12):1892-1899.
- Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. The Captopril-Digoxin Multicenter Research Group. JAMA. Jan 22-29 1988;259(4):539-544.
- A placebo-controlled trial of captopril in refractory chronic congestive heart failure. Captopril Multicenter Research Group. J Am Coll Cardiol. Oct 1983;2(4):755-763.
- Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group. N Engl J Med. Jun 4 1987;316(23):1429-1435.
- Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med. Aug 1 1991;325(5):293-302.
- Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. Aug 1 1991;325(5):303-310.
- Jong P, Yusuf S, Rousseau MF, Ahn SA, Bangdiwala SI. Effect of enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study. Lancet. May 31 2003;361(9372):1843-1848.
- Philbin EF, Rocco TA, Jr., Lindenmuth NW, Ulrich K, Jenkins PL. Systolic versus diastolic heart failure in community practice: clinical features, outcomes, and the use of angiotensin-converting enzyme inhibitors. Am J Med. Dec 1 2000;109(8):605-613.
- Chen HH, Lainchbury JG, Senni M, Bailey KR, Redfield MM. Diastolic heart failure in the community: clinical profile, natural history, therapy, and impact of proposed diagnostic criteria. J Card Fail. Oct 2002;8(5):279-287.
- Shekelle PG, Rich MW, Morton SC, et al. Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials. J Am Coll Cardiol. May 7 2003;41(9):1529-1538.
- Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA. May 10 1995;273(18):1450-1456.
- Flather MD, Yusuf S, Kober 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. May 6 2000;355(9215):1575-1581.
- Lonn E, Roccaforte R, Yi Q, et al. Effect of long-term therapy with ramipril in high-risk women. J Am Coll Cardiol. Aug 21 2002;40(4):693-702.
- Keyhan G, Chen SF, Pilote L. Angiotensin-converting enzyme inhibitors and survival in women and men with heart failure. Eur J Heart Fail. Jun-Jul 2007;9(6-7):594-601.
- Mortality risk and patterns of practice in 4606 acute care patients with congestive heart failure. The relative importance of age, sex, and medical therapy. Clinical Quality Improvement Network Investigators. Arch Intern Med. Aug 12-26 1996;156(15):1669-1673.
- Chin MH, Goldman L. Factors contributing to the hospitalization of patients with congestive heart failure. Am J Public Health. Apr 1997;87(4):643-648.
- Lenzen MJ, Rosengren A, Scholte op Reimer WJ, et al. Management of patients with heart failure in clinical practice: differences between men and women. Heart. Mar 2008;94(3):e10.
- Sheppard R, Behlouli H, Richard H, Pilote L. Effect of gender on treatment, resource utilization, and outcomes in congestive heart failure in Quebec, Canada. Am J Cardiol. Apr 15 2005;95(8):955-959.
- Masoudi FA, Rathore SS, Wang Y, et al. National patterns of use and effectiveness of angiotensin-converting enzyme inhibitors in older patients with heart failure and left ventricular systolic dysfunction. Circulation. Aug 10 2004;110(6):724-731.
- Nieminen MS, Harjola VP, Hochadel M, et al. Gender related differences in patients presenting with acute heart failure. Results from EuroHeart Failure Survey II. Eur J Heart Fail. Feb 2008;10(2):140-148.
- Wright JT, Jr., Dunn JK, Cutler JA, et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. Apr 6 2005;293(13):1595-1608.
- Exner DV, Dries DL, Domanski MJ, Cohn JN. Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N Engl J Med. May 3 2001;344(18):1351-1357.
- Dries DL, Strong MH, Cooper RS, Drazner MH. Efficacy of angiotensin-converting enzyme inhibition in reducing progression from asymptomatic left ventricular dysfunction to symptomatic heart failure in black and white patients. J Am Coll Cardiol. Jul 17 2002;40(2):311-317.
- Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA. May 21, 2003 2003;289(19):2560-2571.
- Kostis JB, Shelton B, Gosselin G, et al. Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). SOLVD Investigators. Am Heart J. Feb 1996;131(2):350-355.
- Morimoto T, Gandhi TK, Fiskio JM, et al. Development and validation of a clinical prediction rule for angiotensin-converting enzyme inhibitor-induced cough. J Gen Intern Med. Jun 2004;19(6):684-691.
- Mackay FJ, Pearce GL, Mann RD. Cough and angiotensin II receptor antagonists: cause or confounding? Br J Clin Pharmacol. Jan 1999;47(1):111-114.
- Shah MR, Granger CB, Bart BA, et al. Sex-related differences in the use and adverse effects of angiotensin-converting enzyme inhibitors in heart failure: the study of patients intolerant of converting enzyme inhibitors registry. Am J Med. Oct 15 2000;109(6):489-492.
- McKelvie RS, Yusuf S, Pericak D, et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation. Sep 7 1999;100(10):1056-1064.
- Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II. Lancet. May 6 2000;355(9215):1582-1587.
- Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet. Sep 6 2003;362(9386):772-776.
- Teo KK, Yusuf S, Pfeffer M, et al. Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a systematic review. Lancet. Oct 5 2002;360(9339):1037-1043.
- Miller DR, Oliveria SA, Berlowitz DR, Fincke BG, Stang P, Lillienfeld DE. Angioedema incidence in US veterans initiating angiotensin-converting enzyme inhibitors. Hypertension. Jun 2008;51(6):1624-1630.