What is there, apart from medication, to treat angina?
Relief measures other than medication include angioplasty and surgery. First, there are some general self-help measures. These have been discussed before but to summarise:
•    stop smoking;
•    lose weight;
•    cut down on alcohol;
•    take exercise;
•    Take life easier by reducing stress.


The use of aspirin as a preventative drug has been discussed a lot in the media recently. What does aspirin do?

Aspirin helps stop blood clotting. It reduces by 25% the risk of a heart attack and helps prevent strokes in people with angina or who have had a heart attack. You only need 75 mg a day and should not take more, unless specified by your doctor; 75 mg is a quarter of an adult 300 mg tablet. It occasionally upsets the stomach and a small number of people with asthma or bronchitis may be sensitive to it (it worsens the wheezing). Overall it is cheap, safe and very effective. Special types of coated aspirin are available for those who get indigestion but they are not always helpful. Taking a compound like Alka-Seltzer is another way of taking aspirin and reducing the chances of a stomach upset; it contains 324 mg aspirin, so you will need to take only a quarter.

I get indigestion on aspirin – is there an alternative?

Clopidogrel (Plavix) 75 mg daily thins the blood to the same degree as aspirin and is used as an alternative. It is only available on prescription. It still may cause indigestion and it may be best to stay on aspirin and use a drug that blocks stomach acid such as omeprazole.

Medication
What relieves the pain of angina? Do I have to take medication?

Angina is relieved after 1–2 minutes by slowing down or stopping activity, or using a nitrate tablet or spray, usually GTN, short for glyceryl trinitrate. If you get pain on walking after a meal and stop to take an indigestion tablet, it will seem as if the tablet has helped. In fact it was the stopping that relieved the pain: this is often how angina and indigestion get confused.
Several drugs are available to stop angina occurring or to deal with an attack. We have already discussed cholesterol-lowering diets and tablets in Chapter 2 and it is essential that people with angina have a cholesterol test and know the result.
Anyone with angina should be prescribed and told how to use sublingual (under the tongue) nitrates and aspirin or clopidogrel. The other medications – oral nitrates, beta-blockers, calcium antagonists and potassium channel activators (discussed below) – are prescribed as necessary. See Table 3.2 for a list of currently available medica tions. Check the trade name against the generic name.

Nitrates
How do the nitrates work?

Nitrates open up the arteries by relaxing the muscle in the artery wall. They relax the coronary arteries to improve the blood flow; by relaxing the peripheral arteries (such as in the legs) and veins, they reduce the work the heart has to do. As the problem is one of too much demand and too little supply, nitrates attempt to rectify the situation by improving supply (by dilating the artery) and reducing demand (the heart pumps against less resistance as the arteries are relaxed).

My mother has been given sublingual nitrates but seems unclear what to do. As I am her carer, what do I need to know?

Sublingual nitrates are taken in tablet or spray form and are absorbed via the veins under the tongue. They are effective in 1– 2 minutes and last 20–30 minutes. They relieve attacks and can be used when your mother fears an attack; for example, she can use them at the bottom of a hill before she starts to climb. Headache is the main side effect.
After you collect them from the chemist, the tablets last only about 8 weeks and have to be stored correctly.
• Keep the tablets in the airtight bottle in which they have been dispensed.
•    After use, close the bottle tightly.
•    Do not put cottonwool, other tablets, or anything else in the bottle with these tablets.
•    Store the tablets in a cool place. When your mother carries them with her, tell her not to put them too close to the heat of her body – she could keep them in a purse or handbag (other people can carry them in a briefcase).
•    If she does not use the tablets within 8 weeks of opening the bottle, get a fresh supply and discard the old tablets. An active tablet produces a slight burning sensation when placed under the tongue. If this does not happen, you should get a fresh supply for her.

The spray lasts 2–3 years but is more expensive. It is useful when attacks are infrequent as it lasts longer in storage. Tablets can be bought over the counter without prescription whereas the spray needs a doctor’s prescription.

I have been given nitrate tablets to swallow. Are these different from the sublingual ones?

Yes, nitrates also come as tablets that are swallowed once or twice daily and can be taken on a regular basis to reduce your angina attacks and improve your ability to take exercise. The commonest are isosorbide mononitrate which are taken twice daily, or in slow release formulations (Imdur, Elantan, Ismo) once daily. They must not be taken more often or the body gets used to them – known as tolerance – and they are then ineffective in relieving angina. Sublingual tablets are only taken when you have, or fear, an angina attack coming on.
There are also nitrate patches which are effective when placed on the skin like a plaster; they have to be taken off after 12 hours or your body again develops tolerance. Used 12 hours on and 12 hours off, they act as a back-up and can be helpful overnight if put on in the evening and taken off in the morning. They should not be used on their own because, with 12 hours off, no angina protection is provided for that period.

Since I have been taking nitrates for my angina, I seem to get headaches. Is this due to my medication and are there any other side effects?

Headache is certainly the most frequent side effect. Occasionally you may get palpitations (see Chapter 6) or flushing and some ¬times the tablets under your tongue make your breath smell. Rarely, and particularly if the tablets are taken within a short while of drinking alcohol or when starving, you might get a dizzy attack, caused by a temporary lowering of blood pressure. If headaches are a problem, the nitrates will be stopped and other drugs substituted.

Beta-blockers
I have been prescribed beta-blockers for my angina. What are these?

These are very important medications. They are the only ones (besides aspirin, cholesterol-lowering tablets and ACE inhibitors) that have been medically proved to lengthen the life of many people with heart problems. Beta-blockers reduce the work that the heart has to do by slowing the heart rate and lowering the blood pressure. They also reduce the force with which the heart muscle contracts, so that it needs less energy. By slowing the heart rate, they allow more time for blood to flow to the heart past the narrowings, and they blunt the heart rate’s response to exercise. If you were to run for a bus, your heart rate might rise to 130 beats per minute (bpm); with a beta-blocker it might not get above 110 bpm, so you would be less likely to develop angina. A slower heart rate is therefore a feature of beta-blocker treatment and one of the main reasons that they are so effective in reducing the number of attacks that people experience, as well as allowing them to walk further. They also help people to live longer after a heart attack and may therefore help protect people with angina from serious complications.
Beta-blockers are swallowed, once or twice daily. The commonest in use are atenolol and bisoprolol but a large number exist. They should never be stopped suddenly because the heart can rebound the other way, and this can lead to severe bouts of chest pain or even a heart attack.

I have been taking beta-blockers regularly. Are there any side effects with this treatment?

Yes, beta-blockers can cause: • wheezing (they should not be given to asthmatics);
•    breathlessness and fatigue (general tiredness with feelings of being ‘worn out’ or ‘washed out’);
•    cold hands and feet and heavy leg muscles (by slowing the circulation);
•    muzzy head with poor concentration and vivid dreams;
•    rarely, depression;
• occasional erection problems in men and reduced sex drive in women.
Do not stop taking your medication if you experience any of these effects. Tell your doctor and your tablets can be changed.

I have been very forgetful lately. Do you think this could be due to the beta-blockers I am taking? Are there any others I could take?

Yes. Some beta-blockers (such as atenolol)are soluble in water and do not cross into the brain, so dreams and confusion or forgetfulness are less common. These are known as hydrophilic
(dissolve in water) types. Others (such aspropranolol)are soluble in fat (lipophilic) and can cross into the brain. Although you may have more side effects with propranolol, you may also find that you are less anxious.

I have noticed that I have a slight tremor. Can beta-blockers relieve tremor and shakiness?

Yes, beta-blockers can be very effective, particularly propranolol, if you have tremor. As a result they can also help people with Parkinson’s disease. It is also claimed that they improve the performance of snooker players and golfers! This is likely where anxiety and tremor are a major problem, of course, but the routine use of beta-blockers to improve performance is not approved of!

If my pulse drops below 50, should I stop taking my beta-blockers?

No. Beta-blockers act to slow the heart. The coronary arteries receive their oxygen and food between the beats, so the slower the rate, the more time the heart has to receive its food supply. Your treatment will only be stopped if, owing to your slow heart rate, your symptoms of lethargy and fatigue become a problem. It is best to reduce the dose first. Do not stop any treatment without your doctor’s advice. Beta-blockers should certainly not be stopped suddenly as this can cause a rebound chest pain and could be very dangerous.

When is the best time to take beta-blockers?

The once-a-day variety such as atenolol or bisoprolol are useful for people who have problems in remembering to take tablets (see question later in this section), and these are often best taken at night. This is a useful time to take them if they make you feel drowsy.

Is it a disaster if I forget to collect my prescription and run out of tablets?

You must try not to run out of your tablets as you may get rebound chest pain. Your chemist will give you some until you get your prescription renewed: it is dangerous to stop beta-blockers suddenly (see question above about stopping tablets suddenly).

My doctor prescribed beta-blockers some time ago and now has put me on nitrates as well. Is this safe?

Yes, the combination is very effective. For example, you may be given atenolol plus isosorbide mononitrate.

Calcium antagonists
What are calcium antagonists (calcium blockers)?

Calcium is an ion (an electrically charged particle) which increases the tone of muscles and strengthens the contraction of the muscle. The muscle in the wall of the artery depends on calcium for its tone, so if the movement of calcium into the muscle cell is ‘antagonised’ or ‘blocked’, the muscle will relax. As the muscle relaxes the artery becomes bigger, blood flow increases and the demands on the heart decrease.

Do calcium antagonists act in the same way as nitrates?

In a way, yes. They both increase the size of arteries but by different mechanisms. In combination they may have an additive effect, so you may be prescribed both.

Can I take calcium antagonists with beta-blockers?

Only some calcium antagonists. Verapamil must never be taken with a beta-blocker because of the danger of slowing the heart too dramatically. Diltiazem is used cautiously by some hospitals. Amlodipine, felodipine and nifedipine are quite safe and effective in combination with beta-blockers. Never mix your medications without first checking with your doctor or pharmacist.

I have not got on well with verapamil so my doctor plans to change my medication to nifedipine. Are there differences between the various types of calcium antagonists?

There are several calcium antagonists on the market and they have some differences which are important. Verapamil and diltiazem slow the heart rate as well as widening blood vessels, so they are a good alternative to beta-blockers, if beta-blockers are not suitable for you (for instance if you have asthma) or they are giving you unacceptable side effects. The calcium antagonists amlodipine, felodipine and nifedipine do not slow your heart rate and are often used in combination with beta-blockers.

Will I experience any side effects with calcium antagonists?

There are plenty of calcium antagonists on the market, so if you are prescribed one that does not suit you, tell your doctor so that your medication can be changed. Two common effects you are likely to experience are headaches and flushing,because these medications open up the arteries.
Another common side effect is swollen ankles and this does not respond to water tablets (diuretics; see the section Treatment in Chapter 5). Ankle swelling may improve as the dose is decreased but often the tablets have to be discontinued. Verapamil and diltiazem are less likely to lead to swollen ankles.
Constipation can be a problem if you are taking verapamil (and more so the older you get). High-fibre diets and lactulose can help but, if constipation becomes a serious problem, your doctor will change you onto another type of calcium antagonist.
Rarely, eye pain and gum problems occur. Calcium antagonists do not usually cause the tiredness that can be a problem with beta-blockers. They may be less effective if you continue to smoke, whereas beta-blocker treatment is not affected by smoking. (Remember smoking causes heart attacks and can kill you.)

Why did my doctor prescribe beta-blockers for me rather than calcium antagonists?

Usually calcium antagonists are prescribed only if beta-blockers are not suitable or are giving side effects. Some calcium antagonists can be combined with beta-blockers to give an additional benefit and all of them can be combined with nitrates (see question above about combining these medications).

I have found that beta-blockers have given me an unfortunate problem, in affecting my love life. My doctor says he will try me on calcium antagonists, but not straight away. Why not?

Your doctor will do this gradually. The beta-blocker must be wound down and the calcium antagonist wound up over a period of time. Calcium antagonists do not give you protection when beta-blockers are suddenly stopped.

Potassium channel activators
I seem to have been given all sorts of medication for my angina over time. My doctor has now said he wants me to try a new type called a potassium channel activator. I have never heard of this one! Will it do any good?

These are medications which work half like a nitrate and half like a calcium antagonist. There is only one available at the moment – nicorandil. It can be used on its own or in combination with the other three types of medication for angina (see Table 3.2). It does not cause swollen ankles, but headaches can be a problem. It is as good as the other medications but not any better, and it is very expensive in comparison. It tends to be used after the other options have been tried and in this way can be very helpful. So if you have tried all the other options, you might –with luck – find that this suits you. Do not drive or operate machinery until settled on nicorandil and your perform ¬ance is not impaired.

My doctor says she would like to try me on ivabradine as I have side effects on atenolol. How is it different?

Ivabradine (Procoralan) is a new drug which slows the heart rate by an electrical action,so it is different from a beta-blocker. It may be used when beta-blockers are not tolerated and when the heart rhythm is regular (in sinus rhythm). Side effects are not common but include temporary visual disturbances (blurring), headache and dizziness. The pulse must be monitored to make sure it’s regular and not below 50 beats per minute. Unlike beta-blockers there is no evidence to date that it prolongs life,but it does relieve angina pain.

Taking your medication
I am rather confused over the various medications available for angina. How many can I take at any one time?

Quite often, too many are taken at any one time! You will need aspirin and, usually, a cholesterol-lowering tablet (usually a statin) to reduce your chances of the coronary narrowings becoming worse. If one angina drug doesn’t work, there is a tendency among doctors to add other medications rather than change the combination. If one drug partly works, it makes sense to increase its strength or add another in but, if it’s not working, it makes no sense to continue it. There is no medical evidence that taking more than two medications for angina is better than one or two used properly. Many people could have their medication simplified, and it is possible that your doctor does not know exactly what you are taking, so always take all your tablets with you when you visit the surgery. If you are on many different tablets, discuss their strengths with your doctor and whether all of them are necessary. Do not make changes on your own. Many medications, taken twice or three times a day, are now in once-a-day formulations which makes life easier.

I am bad at remembering to take tablets. What should I do?

If you are on frequent doses (say three times a day), ask for a once-a-day alternative. For example, if you are on diltiazem 60 mg three times a day and isosorbide mononitrate 20 mg twice a day (five tablets), this could be changed to long-acting diltiazem 200 mg once a day and long-acting mononitrate once a day (that is, two tablets altogether) with the same effect. Beta-blockers are often best taken at night. Any sedative side effects can then be slept off.
Try to establish a routine. Take your medication at the same time of day – with your morning cup of tea or after brushing your teeth. If you are on a lot of tablets, special pill boxes are available, such as the Dosette, that are split into time of day and days of the week: ask your pharmacist about these. Ask your partner or friends to remind you or stick reminders by the phone or on the fridge (use one of those reminder magnets).
Remember not to run out (see a previous question on this). If you have a question about your medication,write it down – most people forget when they go to the doctor. It’s a good idea to ask what each tablet is for and when you should take it. And remember to take all your tablets with you to the surgery – the doctor may not know what you are taking.
If you miss a dose of beta-blockers, take an extra tablet to catch up – others do not need boosting so just get back on schedule.

I have been told that cold remedies react with angina tablets. What can I do if I need them?
Some of these medications react, some don’t. Show your heart tablets to the pharmacist and ask for advice about what you can or cannot take.

Am I allowed to drink alcohol with the medication?
Yes. However, alcohol does widen blood vessels, so the effects may add up with those of nitrates and calcium antagonists to give you more chance of a headache.

Are there any special dietary precautions that I should take while I am on angina medications?
The only precaution is to avoid grapefruit juice as it reacts with some medications in the liver – especially calcium antagonists and some statins. Advice on orange juice is to avoid it within 4 hours of taking your medication.

Are there any new medications for angina in the pipeline?
There are always new ones coming along. Most are variations on what we have already. We always need to see whether they are better than what we have or whether they can be added in to improve what we have. Always beware of exaggerated claims and look carefully at any statistics that are given.

I have heard that a drug called trimetazidine is available – what is this?
Trimetazidine is an interesting drug; it acts to improve oxygen supply by affecting how the cells of the heart work. It does not affect heart rate or blood pressure. It is not available (unless specially requested) in the UK but it is widely available elsewhere. It is an effective drug with minimal indigestion side effects and can be combined with all the other drugs available. It is the first of a class of drugs known as ‘metabolic agents’ because of its action improving how the cells function.

I read in the paper that there is a new drug called ranolozine about to become available – in what way is it different?

Ranolozine (Ranexa) acts a bit like trimetazidine (see above) but also inhibits the build-up of sodium and calcium in the cells, causing relaxation and improving oxygen supply, so angina is reduced. It can be added to other drugs but caution is needed in case there is a clash in the way they are metabolised(broken down). It can cause constipation, nausea and dizziness but these side effects are not common. Some evidence exists that it improves diabetic control. It appears to be a useful new therapy with a good safety profile.

Reference:
All questions are answered through articles indexed in www.PubMed.com and edited by: Dr G. Jackson in Heart Health 4th edition.