Prescribing for angina
The first question when a patient presents with chest pain is ‘what is it?’ but once a diagnosis of angina has been established, what can be done to control it?
Good news is in short supply for NHS workers and their patients, so it is with unsuppressed glee that I can reveal that angina is becoming rarer (probably).1 ‘Probably’ because nobody appears to know what the current prevalence of angina is:2 you would think with general practice records being overwhelmingly computerised and Read-coded that the information would be readily available, but seemingly nobody has bothered to look. In 1993 a community survey put the point prevalence at 1.5% or 2.6% in the over 30 age-group,3 but since then all other manifestations of ischaemic heart disease have been on the retreat1 and so the current prevalence of angina is almost certainly lower.
There are descriptions going back to antiquity of people suffering from symptoms that almost certainly represent angina. The first proper description was by Edward Hyde (1609-1674) in his autobiography The Life of Edward, earl of Clarendon,4 and the first description from a medical source was by William Heberden when he used the terms angina pectoris and pectoris dolor.5
Cardiovascular disease (CVD) is associated with advancing age. Doubtless CVD was around before the 17th century, but relatively few people lived long enough for it to be commonplace, and succumbed to another fatal disease before CVD could take a hold.
The link between atheroma (when cholesterol accumulates in clumps on the inside of arteries – it appears not to affect veins) and CVD was not confirmed in the early days. Once it was proven, a lot of attention was paid to who gets atheroma and why. Work from autopsies during the Korean and Vietnam Wars (one macabre effect of wars is that you get a lot of young men to do post-mortems on who are officially healthy, apart from just having been killed) found that soldiers in their teens already had evidence that atheroma was building up in their arteries. This work was confirmed as late as 1993 when 111 victims under age 35 who died of non-cardiac trauma were examined: like the war reports it was found that nearly 80% had signs of atheroma, with more than 50% arterial narrowing in 20% and more than 75% narrowing in nearly 10%.6
However, things are beginning to look brighter. In 2009, 80,000 people died in the UK due to coronary heart disease (CHD – CVD but where only the heart is affected) compared with 166,000 in 1961).1 There are probably many reasons for this. People are smoking less tobacco and eating healthier diets, but on the other hand the rates of diabetes and obesity are going up. People are exercising more, but from a pretty low baseline: in the less recent past the lot of most people was that extreme physical exertion was a normal part of work and staying alive, so being physically lazy was not an option.
In addition the care of atheroma has improved markedly, both in primary (stopping the atheroma developing in high-risk groups) and in secondary prevention (stopping the atheroma causing too much harm once it is present). A lot of this is down to the efforts of (mainly) primary care. A particular aspect of optimum care is the best use of medications.
What else could it be?
First things first: how do you know your patient has angina? You are on triage duty for the practice and a patient rings in. Or you are in a clinic, and your patient says he has got a fresh symptom.
Typically angina causes a constricting central pain at the front of the chest, which may spread to the jaw, shoulders and arms (especially the inside of the left arm). Some patients will hold a clenched fist up to their chest while describing their pain. The pain comes on with exertion and abates with rest. If your patient is male, older, has CVD risk factors or has already had a CVD event (e.g. a heart attack or a stroke), then this makes angina more likely.7
Yet not all chest pain is caused by angina. Box 1 gives a differential diagnosis for chest pain if it is not coming from your patient’s heart. It is sometimes difficult to be sure about the cause based just on symptom pattern, so err on the side of caution.
Your patient may actually be in the middle of having an acute coronary syndrome (ACS) (a myocardial infarction or heart attack). In this case the pain may be continuing, or may have been present in the previous 12 hours, and there may be signs of heart failure: if this is even a remote possibility, tell a GP colleague and dial 999.
Also, there are some non-cardiac but nonetheless serious causes for chest pain. Box 2 gives some guidance about which patients may be sufficiently unwell as to require urgent admission to hospital.
DRUGS USED IN ANGINA
What follows is a discussion of the common drugs used in angina. The list is not exhaustive, and may be affected by co-morbidity – for example if your patient already has diabetes or high blood pressure, this will affect the drugs used. Also, drugs are only part of the management package, which should include advice about diet, exercise, smoking, alcohol and the rest. But this article is about prescribing.
Glyceryl trinitrate (GTN).
Angina is usually caused by restricted blood supply to the heart muscle (a bit like cramp), and GTN works by both vasodilation (opening out the coronary arteries by relaxing the muscles in the artery walls), and by reducing the volume of blood flowing into the heart which therefore reduces the work the heart has to do. The dose is given under the tongue, and both tablets and a spray are available: the tablets are a bit cheaper, but once opened the bottle has to be discarded after 8 weeks as the tablets go off; the spray costs a bit more but has a much longer shelf-life.
GTN works very quickly (less than a minute) and the effects can last up to 30 minutes. Indeed GTN is sometimes used to diagnose angina because of its rapid action, but GTN also helps pain coming from the oesophagus so it is not completely specific. A second dose can be given 5 minutes after the first if there is no improvement. If the second dose does not work, then you may be dealing with an ACS, in which case it is 999 time.
Because it is a vasodilator, GTN can cause hypotension and a throbbing headache (this makes sense: migraine is thought to be caused by the temporary dilation of cerebral blood vessels) and some people are more sensitive than others to these side effects. Other problems include dizziness and heart-racing. Care should be used when prescribing GTN for anyone already taking a blood-pressure lowering drug as fainting becomes a distinct possibility.
GTN should never be used for someone on treatment for erectile dysfunction as a profound drop in blood pressure can result (sildenafil was actually developed as a treatment for angina before its other uplifting properties were discovered). A break of 24 hours is suggested after taking sildenafil before GTN is safe to use.9 If someone gets angina during sex which has been facilitated by sildenafil, the advice is to ‘stop what you are doing’, wait 10 minutes, and if the pain is still there, dial 999 (i.e. don’t be tempted to use the GTN).
Nitrates are also available as modified-release tablets and patches to give a steady dose of drug. These can be quite helpful. However, if nitrate is in a patient’s blood all the time, then it stops working. A ‘wash out’ period is needed between doses. So long-acting nitrates should not be taken through the night: many formulations of the modified tablets and patches are designed to run out after several hours leaving the night clear, and so a single daily dose should be used in the morning.
Beta-blockers
Your patient has some GTN to use when the angina comes on. The next step is to use something to stop the angina coming on and a beta-blocker or a calcium channel blocker is recommended.10
Ten different beta-blockers are available in the UK to treat angina,11 and choice should be based on patient preference and economy as they all appear equally efficacious. Many need only be taken once a day, which will help with compliance. Some (such as propranolol – all beta-blockers end in ‘-olol’) readily cross the blood-brain barrier and can cause vivid dreams: these dreams are not necessarily unpleasant, and when asking about this side effect your patient may look a bit embarrassed. For patients who have had a heart attack, or who have heart failure as well as angina, this may affect the specific beta-blockers recommended.11
The trick is to build up the dose of beta-blocker to target, or until side effects are too troublesome to bear. Beta-blockers have a very long list of possible adverse effects,11 (which possibly reflects the fact that beta-blockers have been around for a long time, so that all the possible side effects have already happened to somebody) of which the most problematic are probably fatigue, lowered blood pressure, cold hands and feet, and sexual dysfunction.
Beta-blockers work by slowing the heart rate and thus the amount of work the heart has to do. This is all well and good unless your patient already has heart block and a slow pulse anyway. Heart block is one of another long list of reasons why beta-blockers should not be prescribed at all or with great caution.11 Other highlights of the contraindications list are: severe low blood pressure (<90mmHg systolic); heart failure, and asthma or COPD (all beta-blockers can make bronchospasm worse). When it comes to drug interactions, beta-blockers should be used with caution with any drug that lowers blood pressure (including drugs which are being taken deliberately to lower raised blood pressure), and should never be used with verapamil as this can result in your heart stopping.11
Calcium channel blocker
These can be used alone when your patient can’t take a beta-blocker (either because of a contraindication or a problematic side effect), or can be used with a beta-blocker to improve angina control. They are (like GTN) vasodilators but the effect is longer-acting.
The guidelines are not very helpful on the question: ‘What represents control?’ of angina symptoms.12 This will of course determine which patients need extra medication or a referral to a cardiologist. As a rule of thumb, I would suggest that if your patient’s activities are being significantly impaired by the angina, or if they have to use GTN relief more than twice a day (particularly if it gives nasty side effects), then a treatment review is appropriate.
Several products are available and all work as well as each other.13 However, different drugs have slightly different characteristics and so may be more suitable for specific patients: for example verapamil reduces heart rate and so cardiac work, but (as above) is not a great idea in combination with a beta-blocker that does the same thing.
Side effects include what might be expected from a vasodilator: facial flushing; headache; reduced blood pressure; ankle swelling. These may settle with time, but ankle swelling tends to persist. The commonest other adverse effects include dizziness, constipation, nausea and indigestion. Two notable interactions are with statins (increasing the blood level of the statin), which is awkward as nearly all patients with angina will also be on a statin (see later), and grapefruit juice which makes the calcium channel blocker less effective.
First reserves
If both beta blockers and calcium channel blockers can’t be used, or can’t be tolerated, this is the time to wheel out the long-acting nitrates mentioned above. Or failing that there is nicorandil. Nicorandil is a potassium channel activator (these ‘channels’ are all in cell membranes, specifically for the muscle surrounding blood vessels) and so is a vasodilator for both arteries and veins. Accordingly it may lower blood pressure and should be avoided if doing this would pose a problem. In addition it can cause gastrointestinal ulceration, typically of the anus,14 which settles very slowly or not at all when the nicorandil is stopped.
Secondary prevention
The drugs mentioned above are specific for angina. However, angina is caused by atheroma and so is a manifestation of arteriosclerosis. This means that, whatever level it is, your patient’s cholesterol level is high enough to cause mischief and needs to be reduced. Also, if the arteries are clogging up then something to reduce blood stickiness and make it flow better is to be welcomed.
For the cholesterol, ‘high intensity treatment’ is recommended.15 This means atorvastatin in full dose (80mg a day), unless another statin is already being taken without adverse effects. Care needs to be exercised if your patient has liver disease, and statins should not be taken during pregnancy and breastfeeding. If a course of erythromycin or clarithromycin is to be taken for an infection, then the statin should be stopped until the course is completed (otherwise this may precipitate a rather nasty muscle disorder – rhabdomyolysis). Grapefruit juice increases statin blood levels, but only in large quantities – about 1.2L which is around 2 pints.
There is some doubt about how much statins cause muscle pains. Serious muscle disorders can occur with statins, but these are very rare. Milder but troublesome muscle aches are, anecdotally, quite common, but may be relieved by lowering the dose or trying another statin. Stopping the statin for a month to see if the aches go away will not expose your patient to too much risk. Taking a statin also increases the risk of diabetes, which may explain why in primary prevention (compared with secondary prevention) statins are much less impressive at keeping patients alive.16 Statins may also cause nose and throat pain, nosebleeds, and indigestion.15
In angina, aspirin is at present thought to be the best way of reducing blood stickiness and so improve blood flow. It does this by reducing the stickiness of platelets – the small blood cells that are responsible for forming blood clots. Small doses work better than bigger doses, but there is debate about what dose is best: the UK has opted for 75mg a day, yet in other countries different doses are recommended. Though aspirin is first choice, some patients cannot take it or are taking another anti-platelet drug for another reason: in this case there is no point swapping over to aspirin. Some people are allergic to aspirin. Others get indigestion, and for these individuals, using a proton-pump inhibitor (PPI) with the aspirin will often solve the problem.
CONCLUSION
Angina is common, but not as common as it used to be. Being diagnosed with angina usually means a lifetime of pill-taking. Getting the medication balance right may take some time. Also the needs of patients for medication may alter with time, or another relevant disease may come along to complicate things.
CVD is much researched, and there are numerous guidelines to inform decision-making. Probably the top of the pile are the NICE Clinical Knowledge Summaries (CKS). You will see in the reference list multiple entries for NICE/CKS. In truth these are all from (or signposted from) the stem angina guidelines, but their number indicates how much drilling has to be done before you can find the answers you need. NICE used to publish guidance in rather elegant and useable pamphlets. This is, of course, called progress.
REFERENCES
1. British Heart Foundation. Trends in coronary heart disease 1961-2011. 2011.
2. NICE/CKS. Angina. Prevalence. https://cks.nice.org.uk/angina#!backgroundsub:4
3. Angina pectoris - a review of treatment. MeReC Bulletin August 1994:5(8)
4. Hyde E. The Life of Edward, earl of Clarendon, written by himself. 3rd Edition. Oxford, Clarendon Printing House, 1761
5. Heberden W. Some account of a disorder of the breast.
Medical Transactions 1772;2:59-67 London: Royal College of Physicians
6. Joseph A, et al. Manifestations of coronary atherosclerosis in young trauma victims – an autopsy study. J Am Coll Cardiol. 1993 Aug;22(2):459-67.
7. NICE/CKS. Angina. Assessment of stable chest pain. https://cks.nice.org.uk/angina#!diagnosissub
8. NICE/CKS. Chest pain. Scenario: management. https://cks.nice.org.uk/chest-pain#!scenario [
9. NICE/CKS. Angina. Nitrates. https://cks.nice.org.uk/angina#!prescribinginfosub
10. NICE/CKS. Angina. Scenario: New diagnosis. https://cks.nice.org.uk/angina#!scenariorecommendation:1
11. NICE/CKS. Angina. Beta-blockers. https://cks.nice.org.uk/angina#!prescribinginfosub:21
12. NICE/CKS. Scenario: Poor control on treatment. https://cks.nice.org.uk/angina#!scenario:2
13. NICE/CKS. Angina. Calcium channel blockers. https://cks.nice.org.uk/angina#!prescribinginfosub:11
14. NICE/CKS. Angina. Nicorandil. https://cks.nice.org.uk/angina#!prescribinginfosub:27
15. NICE/CKS. Lipid modification – CVD prevention. Scenario: Lipid therapy – secondary prevention of CVD. https://cks.nice.org.uk/lipid-modification-cvd-prevention#!scenario:1
16. Ray KK, et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med. 2010 Jun 28;170(12):1024-31. doi: 10.1001/archinternmed.2010.182.
