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Abstract
The development of angiotensin-converting enzyme inhibitors (ACE inhibitors) has been one of the most remarkable stories in the treatment of cardiovascular diseases. Angiotensin converting enzyme inhibitors have several acute and sustained hemodynamic effects that are beneficial in the presence of left ventricular (LV) dysfunction. They increase cardiac output and stroke volume and reduce systemic vascular resistance as well as pulmonary capillary wedge pressure. The hemodynamic benefits are associated with improvement in the signs and symptoms of congestive heart failure (CHF) as well as decreased mortality, regardless of the severity of CHF. In patients with asymptomatic LV dysfunction, therapy with ACE inhibitors prevented the development of CHF and reduced hospitalization and cardiovascular death. They also increase survival when administered early after an acute myocardial infarction (MI). Most recently, ACE inhibition was associated with improved clinical outcomes in a broad spectrum of high-risk patients with preserved LV function. The mechanism of ACE inhibitors benefits is multifactorial and includes prevention of progressive LV remodeling, prevention of sudden death and arrhythmogenicity and structural stability of the atherosclerotic process. Evidence suggests that ACE inhibitors are underutilized in patients with cardiovascular diseases. Efforts should be directed to prescribe ACE inhibitors to appropriate patients in target doses. It is reasonable to believe that ACE inhibitors have a class effect in the management of LV dysfunction with or without CHF and acute MI. Whether the same is true for ACE inhibitors in the prevention of ischemic events is not known yet.
Abbreviations
ACE
angiotensin-converting enzyme
CAD
coronary artery disease
CHF
congestive heart failure
CONSENSUS
Cooperative North Scandinavian Enalapril Survival Study
GISSI
Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico trial
HOPE
Heart Outcomes Prevention Evaluation
NYHA
New York Heart Association
SAVE
Survival And Ventricular Enlargement study
SMILE
Survival of Myocardial Infarction Long-term Evaluation
SOLVD
Studies Of Left Ventricular Dysfunction
Cited by (0)
Copyright © 2001 American College of Cardiology. Published by Elsevier Inc. All rights reserved.
Watch: What are ACE inhibitors and what do they do in your body?
ACE inhibitors are commonly used to treat heart failure and high blood pressure and are often prescribed to people following a heart attack. Doireann Maddock puts some common questions to Dr Terry McCormack.
What are ACE inhibitors and how do they work?
ACE inhibitors can reduce the activity of an enzyme called angiotensin-converting enzyme, or ACE for short. The enzyme is responsible for hormones that help control your blood pressure. It has a powerful narrowing effect on your blood vessels, which increases your blood pressure. ACE inhibitors inhibit or limit this enzyme, making your blood vessels relax and widen. This, in turn, lowers your blood pressure and improves blood flow to your heart muscle. A quarter of the blood pumped out in each heartbeat flows through the kidneys, so if your heart becomes less efficient, your kidneys also suffer. Therefore, ACE inhibitors improve kidney, as well as heart, function.
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I’d like to sign upWhy have I been prescribed an ACE inhibitor?
They are commonly prescribed if you’ve had a heart attack or if you have heart failure. They are also used to treat high blood pressure (hypertension).
There are various types of ACE inhibitor. What are the main differences?
ACE inhibitors make your blood vessels relax and widen. This, in turn, lowers your blood pressure
The main difference between the ACE inhibitors is how long their effects last; some are short-acting and others are long-acting. If the duration is long, you need to take them less often during the day. For example, perindopril is long-acting and only needs to be taken once a day, whereas captopril is short-acting and needs to be taken three times a day. Each drug comes in a range of strengths and we usually start on a low-strength drug and work our way up to the higher strengths as people get used to them.
Common ace inhibitors include:
- captopril (brand names include Acepril, Acezide, Capoten, Capozide, Capozide LS)
- cilazapril (brand names include Vascase)
- enalapril (brand names include Enalapril, Innovace, Innozide)
- fosinopril (brand names include Fosinopril, Staril)
- imidapril (brand names include Tanatril)
- lisinopril (brand names include Carace, Carace Plus, Lisinopril, Zestoretic, Zestril)
- moexipril (brand names include Perdix)
- perindopril (brand names include Coversyl, Coversyl Plus)
- quinapril (brand names include Accupro, Accuretic)
- ramipril (brand names include Lopace, Ramipril, Triapin, Triapin Mite, Tritace)
- trandolapril (brand names include Gopten, Tarka)
What are the possible side effects?
About one in ten people experience a dry, irritating cough. If you have any side effects, let your GP know as soon as possible. In the event that your GP stops prescribing the ACE inhibitor and gives you alternative medication, it’s worth remembering that it can take eight to 12 weeks for the coughto disappear.
Fewer than one in 100 people have a problem with the blood supply to their kidneys (renal stenosis). There are no specific symptoms in renal stenosis so you should have a routine blood test to check your kidney function one to two weeks after starting the medication. Where early checks indicate a problem such as renal stenosis, patients will be advised to change the medication and there won’t be any lasting damage.
Dr Terry McCormack
Dr Terry McCormack is a principal in general practice in Whitby, North Yorkshire. His cardiovascular interests include managing high blood pressure, lipids and heart failure. He was a member of the International Steering Committee for the Hypertension in the Very Elderly Trial (HYVET) and is Secretary of the British Hypertension Society.
About 1 per cent of people develop an allergic reaction, which causes swollen lips and breathing difficulties. This can develop any time from two weeks to two years after starting to take ACE inhibitors. If this happens, your GP will stop your ACE inhibitor and may prescribe an angiotensin receptor blocker (ARB) instead.
If you develop diarrhoea or vomiting due to a stomach bug, or any dehydrating illness, it’s important to consult your GP as they may advise you to temporarily stop taking your ACE inhibitor and restart when you feel better. The reason for this is that ACE inhibitors can increase the amount of potassium salts in your blood, particularly if you are dehydrated.
Salt reduces the effects of ACE inhibitors, so you should avoid high salt foods and adding extra salt
Salt raises blood pressure and worsens heart failure. It also specifically reduces the effects of ACE inhibitors. You can’t avoid salt completely because it’s in lots of the food we already eat, to some degree. However, you should avoid high salt foods and avoid adding extra salt.
Are there any medications that may be prescribed with ACE inhibitors?
ACE inhibitors are often prescribed with other medications and it’s something we call a synergistic effect. They work well with diuretics, which are drugs that make you pass water, and with calcium channel blockers. With diuretics, ACE inhibitors have an enhanced effect at lowering blood pressure and controlling heart failure. They also help to minimise one of the side effects of calcium channel blockers, which is swollen ankles. If you are prescribed an ACE inhibitor and a diuretic, it’s important to be aware that the combination of the two may cause a sudden drop in blood pressure.So if you feel dizzy or unwell, tell your GP as soon as possible.
Can I get help with paying my prescription?
Medical prescriptions are free in Northern Ireland, Scotland and Wales. They are also free for people in England who meet certain criteria, including people who are:
- under 16 or over 60
- receiving Income Support, JSA, ESA or Universal Credit
- pregnant
- 16-18 and in full-time education
- and/or have certain health conditions, including a continuing disability or diabetes that can't be controlled with diet.
If you aren’t entitled to free prescriptions for your medicines you might be able to save money by buying a Prescription Prepayment Certificate (PPC).
getting help with prescription costs
Why doesn’t my doctor want to prescribe me an ACE inhibitor?
People younger than 55 tend to benefit more from ACE inhibitors. This is because young people with high blood pressure often have a high level of renin in their blood (meaning they are renin sensitive). Renin is an enzyme that is released by the kidneys and plays a role in blood pressure regulation. If too much of it is released, it can raise the levels of the ACE enzyme, which we know can cause a rise in blood pressure.
They work well with diuretics, which are drugs that make you pass water, and with calcium channel blockers
Guidelines from NICE (National Institute for Health and Care Excellence) and the British Hypertension Society recommend ACE inhibitors as the most suitable drug for people under the age of 55. People over 55 are less responsive to renin so, for high blood pressure alone, ACE inhibitors would not be the first drug prescribed.
Black people are also not so sensitive to renin so the NICE guidelines recommend that they are not prescribed ACE inhibitors as a first drug of choice.
It’s a different matter with heart failure because the condition is more common in older people. So in terms of using ACE inhibitors to treat heart failure, the older you are, the more you benefit. However, the drug does have the potential to help people of all ages.
Is there anyone who should never be prescribed ACE inhibitors?
The angiotensin–renin system is involved in growth, therefore we are not sure if it’s wise for pregnant women to use ACE inhibitors. It is difficult to carry out research to test this theory, so the best advice is not to use them if you are pregnant or trying for a baby.
Are there any possible alternatives?
Angiotensin receptor blockers (ARBs) have a similar effect in lowering blood pressure and helping heart failure. They do not affect enzymes like ACE inhibitors do. Instead, they block a receptor that is stimulated by the hormones. Studies have shown that ARBs have the same beneficial effects as ACE inhibitors, but without causing patients to develop a cough.
Because there are more studies showing the benefits of ACE inhibitors in heart failure, they are usually used first. ARBs used to be more expensive than ACE inhibitors but now that many are the same price, ARBs are becoming more popular as the first drug to try for controlling blood pressure.
As with ACE inhibitors, ARBs should not be prescribed if you are pregnant or trying to get pregnant.