A m e r i c a n H e a r t J o u r n a l Augus t , 1977, Volume 94, N u m b e r 2

Editorial i i i

The management of the patient with angina

David Short, M.D. Aberdeen, Scotland

The scope for helping patients with angina has increased enormously over the past decade. When I was an intern working at the National Heart Hospital in London in the 1950s, it was by no means uncommon to see patients with the pale bloated features of myxoedema dragging them- selves to hospital for a check-up-half relieved of their angina, but only half alive. In the 1960s, the beta-blockers were introduced, followed shortly by the operation of saphenous vein bypass. Now, the treatment of angina is well advanced and the great need is for the prevention of the underlying diseases, particularly coronary atheroma.

The basis of the management of a patient with angina is diagnosis in depth. First of all angina must be recognized. It is still often overlooked. Attacks of pain or oppression occurring anywhere in the torso (though usually in the region of the upper or middle sternum) precipitated by effort or emotion, and persisting for a few minutes, must be regarded as anginal. Radiation to one or both arms, the throat, lower jaw, or back provides further confirmation of the diagnosis. DifficUlties arise when the pain is in an atypical site; depen- dent on a combination of exercise with cold or a recent meal; and induced by excitement rather than by effort and the electrocardiogram is normal even when recorded during strenuous effort. 1

From the Cardiac Department, Aberdeen Royal Infirmary, Aberdeen, Scotland.

Received for publication Oct. 27, 1976.

Reprint requests: David Short, M.D., Cardiac Department, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB9 2ZB Scotland.

Secondly, it must be accepted that {malin- gering apart) a history of angina always indicates a reduced coronary reserve. I t has often been claimed tha t hiatus hernia and other disorders of the esophagus may produce an identical symp- tom, but this has never been proved.

Thirdly, it must be realized that a reduced coronary reserve does not necessarily imply narrowing of the coronary arteries, although tha t is by far the commonest cause. In 7 to 10 per cent of cases, angina may be due to other varieties of heart disease which cause either a reduction in coronary blood flow or an increase in myocardial work, or bo th - fo r instance, aortic valve disease, hypertension and, less commonly, cardiomyopa- thy, mitral stenosis, or pulmonary hypertension. Occasionally no evidence of heart disease (or any other disease) can be found,

How often angina is due to non-coronary disease cannot be slated precisely and no doubt varies from place to place. In the postmortem series of Zoll and colleagues ~ all the patients with angina whom they studied showed evidence of heart disease or hypertension. Ninety per cent had coronary disease and the remaining 10 per cent were divided more or less equally between hypertension and valvar disease (aortic or mitral or both). In a recent clinical study ,~ angina was due to aortic valve disease in approximately 3 per cent of the patients, to hypertension in a further 3 per cent, and to other forms of heart disease in 1 per cent. Over a quarter of the patients with coronary disease had associated hypertensive disease and 3 per cent had associated severe aortic valve disease.

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Fourthly, it must be appreciated that even when angina is due basically to coronary arterial narrowing the symptom may be aggravated and the diagnosis complicated by extracardiac dis- ease. In the first place, there are diseases which decrease the oxygen content of the blood or increase the work of the heart-e.g. , anemia and thyrotoxicosis. Moreover, certain diseases-such as chronic cholecystitis, duodenal ulcer, or cervical spondylosis, may cause pain in the chest and aggravate and distort the pain of angina. Anxiety, smoking and obesity are other aggravat- ing factors which need to be considered in treat- ment.

To treat angina rationally it is necessary not only to make a comprehensive diagnosis but also to appreciate the prognosis of different patterns of angina. Certain types of angina are particularly dangerous. Crescendo ang ina - tha t is, angina increasing in severity without any extracardiac cause such as anemia, increasing weight, or a fall in atmospheric temperature, carries a high inci- dence of myocardial infarction and death. Angina which is unresponsive to adequate medical treat- ment also carries a serious prognosis. Recent onset angina carries an increased riskr especially if the onset is sudden. 1 On the other hand, it is not sufficiently appreciated that in many patients angina subsides completely and may not return2.

The question is often asked, "Should every patient with angina be investigated by coronary arteriography?" It can be argued that this is essential if the diagnosis is to be really compre- hensive. In some centers this is the policy, and those who practice it claim tha t it provides information which is essential to rational treat- ment. If the coronary arteries are normal, the patient can be considerably reassured. If there is severe left main stem narrowing, many would consider the risk of medical t rea tment too high and advise operation. While accepting the force of the argument in favor of universal investigation, it is obviously not applicable worldwide because there are not the resources available, nor could the provision of such resources be justified. In my view it is best, in most centers, to concentrate on the investigation of those patients in the high risk categories of crescendo and medically intractable angina and perhaps those with recent abrup t onset.

General principles of treatment

Any remediable factors such as hypertension, severe aortic valve disease, mitral stenosis, anemia, thyrotoxicosis, as well as smoking and obesity, should be corrected. Aggravating factors such as gallbladder disease and duodenal ulcera- tion should be treated, although operation should not as a rule be advised unless it is indicated on other grounds.

Patients with angina should be advised to avoid activities which bring on the pain. This usually means walking more slowly and avoiding exercise after a meal or in the coldest part of the day. They should be specifically warned against lifting and pushing-for instance, lifting heavy furniture or trying to push an automobile which has become stuck. If they can avoid travelling to work in the rush hour they should do so. It may be best to go earlier than usual when the parking is easier. If the patient 's occupation is strenuous and less heavy or demanding work is available, a change should be advised; but unsuitable work is far bet ter than unemployment. If the patient can move to a warm climate, this is to be recom- mended. There is some evidence to suggest tha t drugs such as the contraceptive pill and amitrip- tyline (Tryptizol) increase the risk of myocardial infarction and sudden death; such drugs should therefore be avoided so far as possible.

Nervous factors are very important in angina; indeed Paul White 6 went so far as to say that the nervous sensitivity of a patient was as important as all the pathological factors combined. For this reason an optimistic, reassuring at t i tude is impor- tant. Indeed, it is usually justified; for the prog- nosis of angina is nothing like as bad as it is often thought to be. Statements like, "You have a mild form of angina" and "Your heart is 95 per cent normal" are often appropriate. I t is also impor- tant to avoid unnecessarily frequent review because frequent interrogation regarding symp- toms tends to perpetuate them.

Drug treatment

Glyceryl trinitrate. Glyceryl tr ini trate is still the mainstay of t rea tment and is usually suffi- cient in the mild case. The patient should be instructed to carry his tablets with him constant- ly in a container with a tightly-fitting cap (to avoid loss of potency by evaporation). He should be told to suck (not swallow) one of the tablets at

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Management of angina patients

the onset of pain or oppression. He should be advised to chew the tablet if the pain is severe and to discard it as soon as the symptom has been relieved. He should also be advised, until he is familiar with the effect of the tablet, to sit down or recline after taking it, in order .to minimize the danger of fainting. He should not be advised to lie flat because this increases the work of the heart and tends to prolong the attack. It is also impor- tant to instruct the patient in the prophylactic use of the d r u g - t h a t is, to suck a tablet before starting any exertion which he knows from expe- rience is likely to bring on his angina.

Some patients find that glyceryl trinitrate in the standard dose of 0.5 mg. causes such a head- ache that they prefer to put up with the angina. Such patients should be advised that they are unusually sensitive to the preparation and need a smaller dose (0.3 mg.) or, alternatively, that they should be advised to break the tablets and take half a tablet or less. The trinitrate may be replaced by a less rapid and longer-acting compound such as isosorbide dinitrate (sorbide nitrate) 5 to 20 mg. three times a day. Other patients find glyceryl trinitrate tablets helpful but are afraid of overusing them for fear they will lose their efficacy or lead to harmful side effects. Such patients may be reassured on both accounts and told that as many as 20 tablets have been taken daily for long periods without harm.

There has been some concern about the loss of potency of trinitrate tablets. Earlier preparations using a cocoa base were somewhat unstable, but the modern tablets in a mannitol base retain their activity for at least two years if stored in an air- tight container, protected from light, and kept in a cool dry place. Heat accelerates decomposition, so that tablets kept close to the body might need to be changed rather sooner.

The way glyceryl trinitrate works is still not absolutely certain. It is undoubtedly a coronary vasodilator, but the degree to which it can dilate segments of artery which are the seat of wide- spread atherosclerotic narrowing is uncertain. It usually causes a rapid fall in blood pressure, which decreases the work of the heart. It also dilates the peripheral veins, with consequent pooling of blood in the hands and feet; this reduces the venous return to the heart, and hence its stroke output and work.

Beta-adrenergic blocking drugs. Propranolol

(Inderal) and oxprenolol (Trasicor) were a great advance in treating patients with severe angina. Many new beta-blocking drugs have appeared in the last two or three years, but it is too early to say whether any of these is better than the well- tried preparations. Practolol (Eraldin) should no longer be used for treating chronic angina on account of its occasional serious side-effects. Not all patients are helped by beta-blockade; a few are actually made worse. Nevertheless, most patients improve and the results are often dramatic, particularly in patients with tachy- cardia or other evidence of sympathetic overac- tivity. In patients with associated hypertension, beta-blockade offers a chance of "killing two birds with one stone."

It is wise to start t reatment with a small dose-for example, propranolol 10 mg. twice da i ly -and to double the dose every three or four days until relief is obtained, or the heart rate falls below 60 beats/min. If the angina remains unre- lieved in spite of a reduction of heart rate below 60 beats/min., a larger dose may still be success- ful, but this should be done only with due caution. Care should be taken in patients with a tendency to bronchospasm, because this may be made worse. If there is cardiac enlargement or abnormal ventricular function, beta-blockade should be accompanied by a diuretic but if the resting electrocardiogram is normal this precau- tion is unnecessary. In a recent s t u d y i t was shown that in patients on treatment with propra- nolol, the addition of digoxin in a dose of 0.5 mg. daily was followed by a striking improvement in exercise tolerance. T Since angina often subsides spontaneously, particularly in the summer, it may not be necessary to continue beta-blockade indefinitely. If the patient is getting no angina at all the dose should be gradually reduced, and if the symptom does not return the drug may be stopped and kept in reserve.

Other drugs. With glyceryl trinitrate for the relief of the acute attack and beta-blocking drugs for continuous prophylaxis, the need for other drugs is great ly diminished. Nevertheless, there are patients who are not helped by beta-blockade and for whose frequent attacks of angina, glyceryl trinitrate produces only transient relief. Many attempts have been made to find drugs with a more prolonged action than glyceryl trinitrate but with limited success. Isosorbide dinitrate has

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been ment ioned as a subs t i tu te for glyceryl trini- t ra te in pat ients who get a headache with the la t te r drug. The re are prepara t ions which the makers claim can be chewed for relief of an a t t ack or swallowed for prophylact ic effect. Delayed release t r ini t r in (Sustac) is somet imes helpful in pat ients with noc turna l angina. A mild t ranqui l -

�9 izer, such as diazepam (Valium) m a y help an anxious or excitable pa t ient over a par t icular ly stressful period, bu t s tronger hypnot ics have the disadvantage tha t they rarely abolish the a t tacks and often make the pa t ien t too confused to take his t r in i t ra te properly. In such cases, a whisky nightcap is often effective. Perhexil ine malea te (Pexid) has sometimes been dramat ica l ly success- ful in relieving angina which has been resis tant to o ther t r ea tmen t including beta-blockade. Vera- pamil hydrochlor ide (Cordilox) and prenylamine (Synadrin) have also been repor ted effective in some patients. The value of an t icoagulan t t reat- ment and clofibrate (Atromid-S) now appears to be negligible.

Surgical treatment

The operat ion of saphenous vein bypass is a logical answer to what is in most cases basically a mechanical problem. In experienced hands, the operat ion carries a very low mor ta l i ty ra te and it is often dramat ica l ly successful in relieving severe angina which has proved resis tant to full medical t r e a tme n t including beta-blockade. In random- ized control trials of medical versus surgical t r ea tment , 8-~~ the evidence s t rongly points to be t t e r cardiac funct ion in pat ients t r ea ted surgi- cally, though the operat ion does not. appear to a l ter the course of ischemic hea r t disease or to prolong life.

Most pat ients with angina can live a more or less normal life with the help of glyceryl t r in i t ra te and beta-blocking drugs, and a considerable proport ion will lose their angina al together . O the r s will develop myocardia l infarct ion or die suddenly whatever is donel The only clear indica- t ion for saphenous vein bypass a t present is angina which causes pe r s i s t en t disability af ter any remediable factors have been corrected and the medical a r m a m e n t a r i u m has been fully tried. Such pat ients should be ser iously considered for operation, par t icular ly if the e lec t rocardiogram and x-ray films show only slight myocardia l damage.

Treatment of recent onset and crescendo angina

Recent onset and crescendo angina, often referred to as uns table angina, carry a high risk of myocardia l infarct ion or sudden death. If the angina appears only with effort, i t is usual ly sufficient to insist on complete bodily and men ta l rest, reinforced b y sedat ion if necessary. This often breaks the vicious circle, so tha t the pa t ien t m ay resume act ivi ty wi thout the re tu rn of angina. I f the a t tacks come on at rest as well as with effort the s i tua t ion is more dangerous and the pa t ien t should come under close observat ion in hospital . T r e a t m e n t with adequa te doses of a beta-blocker should be given as soon as possible unless there is bronchospasm or some o ther cont ra indica t ion to the use of such drugs. I f anxie ty is a factor, as it of ten is, sedat ion is logical. Wi th such t r e a t m e n t the majo r i ty of pat ients come under control . Ant icoagulan t ther- apy, e i ther with hepar in or warfarin, has its advocates though it is by no means always successful in aver t ing myocard ia l infarction. Th rombo ly t i c t r ea tmen t , using strepokinase, is cur ren t ly being tr ied with some promising results. Persis tence of symptoms in spite of full medical t r e a t m e n t is an indicat ion for urgent coronary ar te r iography with a view to coronary bypass surgery. A prospective contro l trial is in progress to compare the results of medical and surgical t r e a t m e n t in uns table angina. I' P re l iminary results indicate t h a t the mor ta l i ty ra te is the same in bo th groups, bu t long-term relief of pain is be t t e r in the surgical group.

REFERENCES 1. Short, D., and Stowers, M.: Earliest symptoms of coro-

nary heart disease and their recognition, Br. Med. J. 2:387, 1972.

2. Zoll, P. M., Wessler, S., and Blumgart, H. L.: Angina pectoris: a clinical and pathological correlation, Am. J. Med. 1 1:331, 1951.

3. Short, D., and Stowers, M.: Observations on the etiology and course of angina pectoris {Submitted for publica- tion}.

4. Duncan, B., Fulton, M., Morrison, S. L., Lutz, W., Donald, K. W., Kerr, F., Kirby, B. J., Julian, D. G., and Oliver, M. F.: Prognosis of new and worsening angina pectoris, Br. Med. J. 1:981, 1976.

5. Kannel, W. B., and Feinleib, M.: Natural history of angina pectoris in the Framingham study-prognosis and survival, Am. J. Cardiol. 29-154, 1972.

6. White, P.: Heart disease, 3rd ed, New York, 1947, Macmillan Publishing Co., Inc., p. 824.

7. Crawford, M. H., Le Winter, M. M., O'Rourke, R. A., Karliner, J. S., and Ross, J.: Combined propranolol and

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digoxin therapy in angina pectoris, Ann. Intern. Med. 83:449, 1975.

8. Barry, W. H., Pfeiffer, J. F., Lipton, M. J., Tilkian, A. G., Hultgren, H. N.: Effects of coronary artery by-pass grafting on resting and exercise hemodynamics in patients with stable angina pectoris, Am. J. Cardiol. 37:823, 1976.

9. Guinn, G. A., and Mathur, V. S.: Surgical vs. medical treatment for stable angina pectoris: prospective randomized study with 1-4 year follow-up, European Congress of Cardiology, Amsterdam, 1976.

10. Kloster, F . E., Kremkau, E. L., Rahimtoola, S. H., Griswold, H. E., Ritzmann, L. W., and Starr, A.: Prospec- tive randomized study of coronary by-pass surgery for chronic stable angina, European Congress of Cardiology, Amsterdam, 1976.

11. National Co-operative Study Group to compare medical and surgical therapy in unstable angina pectoris I. Report of protocol and patient population, Am. J . Cardiol. 37:896, 1976.

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