Guidelines AMI 1996.PDF Biblio 1

8/12/2019 Guidelines AMI 1996.PDF Biblio 1

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European H eart Journal (1996)17, 4363

Guidelines

Acute myocardial infarction: pre-hospital and in-hospital

managementThe Task Force on the Management of Acute Myocardial Infarction of the

European Society of Cardiology

Introduction

The management of acute myocardial infarction hasundergonemajor changes in recent years. Good practicecan now be based on sound evidence derived fromwell-conducted clinical trials. Because of this, the

European Society of Cardiology decided that it wasopportune to provide guidelines and appointed a TaskForce to formulate these. It must be recognised, how-ever, that many aspects of treatment, such as the man-agement of cardiac arrest and shock, depend uponexperience rather than upon randomized controlledexperiments. Furthermore, even when excellent clinicaltrials have been undertaken, their results are open tointerpretation. Finally, treatment optionsmaybelimitedby resources; cost-effectiveness is an important issuewhen deciding upon therapeutic strategies.

In setting out these guidelines, the Task Forcehas attempted to define which treatment strategies arebased on unequivocal evidence and which are open to

genuine differences of opinion. As always with guide-lines, they are not prescriptive. Patients vary so muchfrom oneanother that individual careis paramount andthere is still an important place for clinical judgment,experienceand common sense.

The natural history of acute myocardial

infarction

Thetruenatural history of myocardial infarction is hardto establish for a number of reasons: the commonoccurrence of silent infarction, the frequency of acute

coronary death outside hospital and the varyingmethodsused in thediagnosis of thecondition. Commu-nity studies[1,2] have consistently shown that the overallfatality of acuteheart attacks in thefirst month is about

50%, and of thesedeathsabout one-half occur within thefirst 2h. This high mortality seems to have altered littleover the last 30 years. By contrast with communitymortality, there has been a profound fall in the fatalityof those treated in hospital. Prior to the introduction ofcoronary careunits in the1960s, thein-hospital mortal-

ity seemsto haveaveraged some2530%[3]

. A systematicreview of mortality studiesin thepre-thrombolytic era ofthemid-1980s showed an average fatality of 18%[4]. Theoverall one-month mortality has sincebeen reduced, butremains high in spiteof the widespread use of thrombo-lytic drugs and aspirin. Thus, in the recent M ONICA(monitoring trends and determinants in cardiovasculardisease) review of five cities, the 28 day mortality was1327%[5]. Other studies have reported one monthmortality figures of 1020%[610].

It was found many years ago that certain factorswere predictiveof death in patientsadmitted to hospitalwith myocardial infarction[3]. Chief among these wereage, previous medical history (diabetes, previous infarc-

tion) indicators of large infarct size, including site ofinfarction (anterior vs inferior), low initial blood pres-sure, the presence of pulmonary congestion and theextent of ischaemia asexpressed by ST elevation and/ordepression on the electrocardiogram. These factorsremain operative today.

Aims of management

While the primary concern of physicians is to preventdeath, those caring for victims of myocardial infarctionaim to minimize the patients discomfort and distressand to limit the extent of myocardial damage. T he care

can be divided conveniently into three phases:

(1) Emergency carewhen themain considerationsaretorelieve pain and to prevent or treat cardiac arrest.

(2) Early care in which the chief considerations are toinitiate reperfusion therapy to limit infarct sizeand to prevent infarct extension and expansionand to treat immediatecomplications such as pumpfailure, shock and life-threatening arrhythmias.

(3) Subsequent care in which the complications thatusually ensuelater are addressed, and considerationis given to preventingfurther infarction and death.

Key Words: M yocardial infarction, drug therapy, ischae-mic heart disease.

Requests for reprints to: European Heart Journal W. B. Saunders2428 Oval Road, London NW1 7DX .

Correspondence:Professor D. J ulian, Flat 1, 7 Netherhall Gardens,London NW3 5RN .

0195-668X/96/010043+21 $12.00/0 1996 The European Society of Cardiology


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These phases may correspond to pre-hospital care, thecoronary careunit (CCU ), and thepost CCU ward, butthereis much overlap and anycategorization of thiskindis artificial.

Emergency care

I niti al diagnosis

A working diagnosis of myocardial infarction must firstbe made. This is usually based on the history of severechest pain lastingfor 15min or more, not responding tonitroglycerine. But the pain may not be severe and, inthe elderly particularly, other presentations such asdyspnoea, faintness or syncope are common. I mportantclues are a previous history of coronary disease, andradiation of thepain to theneck, lower jaw, or left arm.There are no individual physical signs diagnostic ofmyocardial infarction, but most patients have evidence

of autonomic nervous system activation (pallor, sweat-ing) and either hypotension or a narrow pulse pressure.Features may also include irregularities of the pulse,bradycardia or tachycardia, a third heart sound andbasal rales. An electrocardiogramshould beobtained assoon as possible. Even at an early stage, the ECG isseldom normal[11,12]. However, theECG isoften equivo-cal in the early hours and even in proven infarction itmay never show the classical features of ST elevationand new Q waves. R epeated ECG recordings should beobtained and, when possible, the current ECG shouldbe compared with previous records. ECG monitoringshould beinitiated as soon as possiblein all patients todetect life-threatening arrhythmias. When the diagnosis

is in doubt, rapid testing of serum markers is valuable.In difficult cases, echocardiography and coronaryangiography may behelpful.

Relief of pain, breathlessness and anxiety

Relief of pain is of paramount importance, not only forhumane reasons but because thepain is associated withsympathetic activation which causes vasoconstrictionand increases the work of the heart. Intravenousopioids morphine or, where available, diamorphine are the analgesics most commonly used in this con-

text; intramuscular injections should be avoided. Re-peated doses may be necessary. Side-effects includenausea and vomiting, hypotension with bradycardia,and respiratory depression. Antiemetics may be admin-istered concurrently with opioids. T he hypotension andbradycardia will usually respond to atropine, and respir-atory depression to naloxone, which should always beavailableIf opioids fail to relievethepain after repeatedadministration, intravenousbeta-blockers or nitrates areoften effective. Paramedics have a limited choice ofnon-addictiveopioidsthat they may use, theavailabilityof which varies fromcountry to country. Oxygen should

beadministered especially to thosewho arebreathlessorwho haveany features of heart failure or shock.

Anxiety is a natural response to the pain and tothe circumstances surrounding a heart attack. Reassur-anceof patients and thoseclosely associated with themis of great importance. If the patient becomes exces-sively disturbed, it may be appropriate to administer atranquilliser, but opioids are frequently all that isrequired.

Cardi ac ar rest

Those not trained or equipped to undertake advancedlife support should start basic life support as recom-mended by TheEuropean Resuscitation Council[13].

Trained paramedics and other health professionalsshould undertake advanced life support, asdescribed in

theguidelines of theEuropeanResuscitation Council[14].

Early care

Restoring and maintaining patency of the

infarct related artery

For patientswith theclinical presentation of myocardialinfarction and with ST elevation or bundle branchblock, early reperfusion should be attempted.

. M ore than 100000 patientshave been randomized in trials of thrombolysis vs con-trol, or one thrombolytic strategy compared withanother[1520]. For patients within 12h of the onset ofsymptoms of infarction, the overall evidence for thebenefit of treatment with thrombolysis is overwhelming.

For those presenting within 6h of symptom on-set, and ST elevation or bundle branch block, approxi-mately 30deathsareprevented per 1000patientstreated,with 20 deaths prevented per 1000 patients treated forthose between 7 and 12h. Beyond 12h there is noconvincing evidence of benefit for thegroup asa whole.

TheISIS-2[16] study demonstrated theimportant

additional benefit of aspirin so that there was a com-bined reduction of approximately 50 lives per 1000patients treated. There is consistency of benefit acrosspre-stratified subgroups and across the range of dataderived subgroup analyses. Overall, the largestabsolutebenefit is seen amongpatients with thehighest risk, eventhough the proportional benefit may be similar. Thus,more lives are saved per 1000 higher risk patientstreated; for example, among those over 65 years of age,those with presenting systolic pressure


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Time to treatment. M ost benefit is seen in those treatedsoonest after the onset of symptoms. An analysis ofstudies in which patients were randomized to pre-hospital or in-hospital thrombolysis suggests that savingan hour reduces mortality significantly[21], but the rela-tively small size of these studies precludes precise quan-tification of the benefit. The fibrinolytic overview[15]

reported a progressive decrease of about 16 deaths perhour of delay per 1000patientstreated. Thiscalculation,based on studies in which the timeto treatment was notrandomized, must be interpreted with caution becausethetime to presentation is not random.

H azards of thrombolysis. Thrombolytic therapy isassociated with a small but significant excess of approxi-mately 39extrastrokesper 1000patientstreated[15]withall of theexcess hazard appearing on the first day aftertreatment. The early strokes are largely attributable tocerebral haemorrhage; later strokes are more frequentlythrombotic or embolic. There is a non-significant trendfor fewer thrombo-embolic strokes in thelater period in

those treated with thrombolysis. Part of the overallexcess of stroke is among patients who subsequently dieand is accounted for in the overall mortality reduction(19excessper 1000). Thus, thereis anexcessof approxi-mately two non-fatal strokes per 1000 patients treated.Of these, half aremoderately or severely disabling. Therisk of stroke varies with age. There is a substantiallyincreased risk for those above75 years of age and alsofor those with systolic hypertension. Other major non-cerebral bleeds, requiring blood transfusion or that arelife-threatening, occur in about 7 per 1000 patientstreated. No specific subgroup is associated with anexcessof bleeds, but smaller studieshavedemonstrated aclear association between arterial and venous puncturesand the development of major haematomas. The risksare increased if arterial punctures are performed in thepresence of a thrombolytic agent.

Administration of streptokinase and anistreplasemay be associated with hypotension, but severe allergicreactions arerare. Routine administration of hydrocorti-soneis not indicated. Wherehypotension occurs, it shouldbemanaged by temporarily halting theinfusion, lyingthepatient flat or elevating thefeet. Occasionally atropineorintravascular volume expansion may berequired.

Comparison of thrombolytic agents.Neither the Interna-tional Trial[19] nor the Third International Study of

Infarct Survival (ISIS 3)[17]

found a differencein mortal-ity between theuseof streptokinaseand tissueplasmino-gen activator or anistreplase. Furthermore, the additionof subcutaneous heparin did not reduce mortality com-pared with theuseof no heparin. However, theGU STOTrial (Global Utilisation of Streptokinase and TissuePlasminogen Activator for occluded coronary ar-teries)[20] employed an accelerated t-PA (tissue typeplasminogen activator) regimen given over 90min ratherthan thepreviously conventional period of 3h. A cceler-ated t-PA with concomitant aPTT (activated partialthromboplastin time) adjusted intravenous heparin was

reported to result in 10 fewer deaths per 1000 patientstreated. The risk of stroke is higher with t-PA oranistreplase than with streptokinase[16,20]. I n theGUSTO trial, there were three per 1000 additionalstrokeswith accelerated t-PA and heparin in comparisonwith streptokinase and subcutaneous heparin[20], butonly one of these survived with a residual deficit. Inassessing thenet clinical benefit, this must betaken intoaccount with the reduced death ratein the t-PA group.The choice of reperfusion strategy will depend on anindividual assessment of risk, and also on factorssuch asavailability and cost benefit[22].

Cli nical implications. Based upon the substantial evi-dencenow accumulated, there is unequivocal benefit, interms of morbidity and mortality for prompt treatmentof acute myocardial infarction with thrombolysis andaspirin, the two agents being additive in their effect.Where appropriate facilities exist, with trained medicalor paramedical staff, pre-hospital thrombolysis may beinstituted provided that the patient exhibits the clinical

features of myocardial infarction and the ECG showsST elevation or bundle branch block.Unless clearly contraindicated, patients with infarc-tion, as diagnosed by clinical symptoms and STsegment elevation or bundle branch block, shouldreceive aspirin and thrombolytic therapy with theminimum of delay. If the first ECG does not showdiagnostic changes, frequent or continuous ECGrecordings should beobtained. Rapid enzyme analy-sis, echocardiography and, occasionally, coronaryangiography may be helpful. A realistic aim is toinitiate thrombolysis within 90min of the patientcalling for medical treatment (call to needle time).In patients with slowly evolving, or stuttering myo-cardial infarction, a series of ECGs and clinicalassessments should be performed to detect evolvinginfarction (with rapid cardiac enzyme analysis, ifavailable).Thrombolytictherapy should not begiven to patientsin whom:The potential for benefit is low, e.g. if the ECGremains normal, or demonstrates only T wavechanges as these patients are at low risk but exper-ience all of the hazards of therapy. Trials have notdemonstrated benefit in those with ST depression,even though the risk in these patients is relativelyhigh; they havenot, however, excluded thepossibility

of some benefit;infarction has been established for more than 12h,unless there is evidence of ongoing ischaemia, withtheECG criteria for thrombolysis.

Contra-indications to thrombolyt ic therapyStrokeRecent major trauma/surgery/head injury (withinpreceding 3 weeks)Gastro-intestinal bleeding within the last monthK nown bleeding disorderDissecting aneurysm

Guidelines on acute myocardial infarcti on 45

Eur Heart J , Vol. 17, J anuary 1996


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Relative contra-indications

Transient ischaemic attack in preceding 6 monthsCoumadin/warfarin therapyPregnancyNon-compressible puncturesTraumatic resuscitationRefractory hypertension (systolic blood pressure>180mmHg)Recent retinal laser treatment

Re-administrati on of thrombolyt ic agent. I f there is evi-dence of re-occlusion or reinfarction with recurrenceofST elevation or bundle branch block, further thrombo-lytic therapy should begiven, or angioplasty considered.Streptokinase and anistreplase should not be re-administered in the period between 5 days and a mini-mumof 2 years followinginitial treatment with either ofthese drugs. Antibodies to streptokinase persist for at

least 2 years, at levels which can impair its activity.Alteplase(t-PA) andurokinasedo not result in antibodyformation.

Adjunctive antithrombotic and antiplatelet therapy. Theindependent and additive benefits of aspirin have beendescribed above. It is not clear whether aspirin worksbyenhancing thrombolysis, preventing reocclusion or bylimiting the microvascular effects of platelet activation.In studies on latereocclusion, aspirin was moreeffectivein preventing recurrent clinical events than in main-taining patency[23]. Thefirst dose of 150160mg should

be chewed, and the same dosage given orally dailythereafter.

Heparin has been extensively tested after throm-bolysis, especially with tissue plasminogen activator.Heparin does not improve immediate clot lysis[24]

but coronary patency evaluated in the hours or daysfollowing thrombolytic therapy with tissueplasminogenactivator appears to be better with intravenousheparin[25,26]. No difference in patency was apparent inpatients treated with either subcutaneousor intravenousheparin and streptokinase[27]. Prolonged intravenousheparin administration has not been shown to preventreocclusion after angiographically proven successfulcoronary thrombolysis, nor has intravenous heparinfollowed by coumadin[28]. Heparin infusion after tissueplasminogen activator therapy may be discontinuedafter 2448h[29]. Closemonitoring of heparin therapy ismandatory; aPTT valuesover 90sarecorrelated with an

unacceptable risk of cerebral bleeding. In the I SIS-3trial[17], subcutaneous heparin (12500b.d.) did notaffect mortality when combined with aspirin andstreptokinase, duteplase, or anistreplase.

()The role of coronary angioplasty (PTCA) during theearly hours of myocardial infarction can bedivided intoprimary angioplasty, angioplasty combined with throm-bolytic therapy, and rescue angioplasty after failedthrombolysis.

M et hods of administrat ion

Table 1 Thrombolyt ic regimens for acute myocardial infarction

Initial treatment Heparin therapy Specificcontra-indications

Streptokinase(SK ) 15 million units Noneor Prior (>5 days)

100ml of 5% dextrose subcutaneous SK /anistreplaseor 09% salineover 3060min 12 500u b.d.

Anistreplase 30 units in 35 min i.v. Prior SK oranistreplase >5 days

K nown allergy toSK /anistreplase

A lteplase (t PA ) 15 mg i .v. bolus i.v. for 48 h*075mg . kg1 over 30min

then 05mg . kg1

over 60min i.v.Total dosage not to

exceed 100mg.Urokinase** 2 million units as an i.v. i.v. for 48h*

bolus or 15 million unitsbolus +15 million units

over 1h

Thistabledescribesfrequently used thrombolyticregimens. Alternativestrategiesandnewer agentsmay confer advantages over these regimens but the potential advantages havenot been validatedin large scale studies.*Dosage determined by aPTT.**N ot licensed in some countries for usein myocardial infarction.N.B. Aspirin should begiven to all patients without contraindications.

46 Guidelines on acute myocardial infarction



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Primary angioplasty. This is defined as PTCA withoutprior or concomitant thrombolytic therapy, and is atherapeutic option only when rapid access (


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Thedegreeof failuremay becategorized accord-ing to the K illip classification[41]: class 1: no rales orthird heart sound; class 2: rales over less than 50% of thelung fields or third heart sound; class 3: rales over 50%of thelung fields; class 4: shock.

Oxygen should beadministered early by mask or intra-nasally, but caution is necessary in the presence ofchronic pulmonary disease.

M inor degreesof failureoften respondquickly todiuretics, such as frusemide 1040mg given slowly in-travenously, repeated at 14 hourly intervals, if neces-sary. If there is no satisfactory response, intravenousnitroglycerine or oral nitrates are indicated. The doseshould be titrated while monitoring blood pressure toavoid hypotension. The initiation of ACE therapyshould be considered within the next 2448h in theabsence of hypotension or renal failure.

Oxygen should be administered and a loop diureticgiven as above. U nless thepatient is hypotensive, intra-venous nitroglycerine should be given, starting with025g.kg1 per minute, and increasing every 5minuntil a fall in blood pressureby 15mmHg is observed orthesystolic blood pressurefalls to 90mmHg. Consider-ation should be given to measuring the pulmonaryartery and wedgepressures, and thecardiac output witha balloon flotation catheter with a view to obtaining awedge pressure of less than 20mmHg and a cardiacindex in excess of 2 l . min1.

Inotropic agents may be of value if there ishypotension. If signs of renal hypoperfusion arepresent, dopamine is recommended intravenously in adosage of 2550g.kg1 . min1. If pulmonary con-gestion is dominant, dobutamine is preferred with ainitial dosage of 25g.kg1 . min1. This may beincreased gradually at 510min intervals up to10g.kg1 . min1 or until haemodynamic improve-ment is achieved. ACE therapy and phosphodiesteraseinhibitors may also be considered.

Theblood gases should be checked. Continuouspositive pressure airways pressure may be indicated ifan oxygen tension of more than 60mmHg cannot bemaintained inspite of 100% oxygen delivered at810l . min1 by mask and the adequate use ofbronchodilators.

Cardiogenic shock. Cardiogenic shock is defined as asystolic blood pressure


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intravenousnitroglycerine, may producesomeimprove-ment if there is no cardiogenic shock, but intra-aorticballoon counterpulsation is the most effective methodof providing circulatory support while preparing forsurgery. Operation offers the only chance of survival inlargepost-infarction VSDs with cardiogenic shock[47,48].Theprimary goal of early surgery is the reliable closureof the defect using the technique of patch augmenta-tion[49]. Pre-operative coronary angiography should beperformed provided it does not compromisethehaemo-dynamic status or cause unduedelay to surgery. Bypassgrafts are inserted as necessary. Predictors of poorpostoperative outcome are cardiogenic shock, posteriorlocation, right ventricular dysfunction, age, and longdelay between septal rupture and surgery[47,48]. Hospitalmortality after surgery is estimated to bebetween 25and60%[50,51], and 95% of survivors are NY HA I or I I [50].

M ost cases of mitral regurgitation after myocardialinfarction are mild and the reflux is transitory. In a

minority of patients, however, major acuteregurgitationis a catastrophic complication that is amendable toaggressive therapy if promptly diagnosed and treatedsurgically. Theincidence of moderately severe or severemitral regurgitation is about 4% and the mortalitywithout surgery high at about 24%[52]. It is usuallyassociated with significant narrowing of both the rightand left circumflex coronary arterieswith posteromedialpapillary muscle involvement.

Cardiogenic shock and pulmonary oedema withsevere mitral regurgitation require emergency surgery.Intra-aortic balloon pump placement may be helpfulduring preparation[50]. Coronary angiography is per-formed if the patients condition permits. In congestive

heart failure, primary catheterization and reperfusion ofthe infarct-related artery by thrombolysis or PTCA canbe attempted.

Valve replacement is the procedure of choice inpapillary muscle dysfunction and rupture, although re-pair can beattempted in selected cases[53]., Revasculariz-ation is indicated for major vessel obstruction.

A rr hythmias and conduction distur bances

Arrhythmias and conduction disturbances areextremelycommon during theearly hoursafter myocardial infarc-tion. I n some cases, such asventricular tachycardia and

ventricular fibrillation, they are life threatening andrequire immediate correction. Often, however, arrhyth-mias are not in themselves hazardous, but are a mani-festation of a serious underlying disorder, such ascontinuing ischaemia, vagal overactivity, or electrolytedisturbance, that requires attention. The necessity fortreatment and its urgency depend mainly upon thehaemodynamic consequences of the rhythm disorder.

Ventricular ectopic rhythms.Ventricular ectopic beatsare almost universal on the first day, and complex

arrhythmias (multiform complexes, short runs, or theR-on-T phenomenon) are common. Their value as pre-dictors of ventricular fibrillation is questionable; eitherventricular fibrillation follows so quickly that no pro-phylactic measures can be taken or no serious arrhyth-mia ensues.

Ventricular tachycardia.Short runsof ventricular tachy-cardia may bewell tolerated and not require treatment,but more prolonged episodes may cause hypotensionand heart failure. L ignocaine is thedrug of first choice,but several other agents are also effective. An initialloading dosageof 1mg . kg1 of intravenouslignocaineis usually given, with half this dosebeing repeated every810min to a maximum of 4mg . kg1. This may befollowed by an intravenous infusion to prevent recur-rences. Countershock is indicated if haemodynamicallysignificant ventricular tachycardia persists.

It is important to differentiate true ventriculartachycardia from accelerated idioventricular rhythm,usually a harmless consequenceof reperfusion, in which

the ventricular rate is less than 120 beats. min1

.

Ventricular fibrillation.When a defibrillator is available,immediate defibrillation should be performed. If it isnot, a precordial thump is worth trying. Therecommen-dations of the European Resuscitation Council shouldbe followed (Fig. 1)[14].

Atrial fibrillation complicates some 1520% of myocar-dial infarctions, and is frequently associated with severeleft ventricular damage and heart failure. It is usuallyself-limited. Episodes may last from minutes to hours,and are often repetitive. In many cases, the ventricular

rate is not fast, the arrhythmia is well tolerated, and notreatment is required. In other instances, the fast ratecontributes to heart failure and prompt treatment isneeded. Digoxin is effective in slowing the ratein manycases, but amiodaronemaybemoreefficaciousin termi-nating the arrhythmia[54]. Countershock may also beused, but should only be employed if mandatory asrecurrences are so common.

Other supraventricular tachycardiasarerare, butusually self-limited. They may respond to carotid sinuspressure. Beta-blockers may be effective, if not contra-indicated, but verapamil is not recommended. Counter-shock should be employed if the arrhythmia is poorlytolerated.

Sinus bradycardia is common in thefirsthour, especiallyin inferior infarction. In somecases, opioidsarerespon-sible. It may be accompanied by quite severe hypoten-sion, in which case it should be treated by intravenousatropine, starting with a dosage of 0305mg, repeatedup to a total of 1520mg. Later in the course ofmyocardial infarction, it is usually a favourablesignandrequires no treatment. Occasionally it may, however, beassociated with hypotension. If it then fails to respondtoatropine, temporary pacing may be advisable.




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First degreeheart block needs no treatment.Type I second degree (Wenckebach) AV (atrio-

ventricular) block is usually associated with inferiorinfarction and seldom causes adverse haemodynamiceffects. Should it do so, however, atropine should begiven first; if this fails, pacing should beinstituted.

Type II second degree (Mobitz) and completeAV block are indications for the insertion of a pacingelectrode. Pacing should be undertaken if a slow heart

rate appears to be a cause of hypotension or heartfailure. If the haemodynamic disturbance is severe,consideration should be given to AV sequential pacing.

Asystolemay follow AV block, bi- or trifascicu-lar block, or electrical countershock. If a pacing elec-trodeis in place, pacingshould beattempted. Otherwise,chest compression and ventilation should be initiated,and external pacing started.

A transvenous pacing electrode should be in-serted, as discussed above, in the presenceof advancedatrio-ventricular block, and considered if bifascicular ortrifascicular block develop. M any cardiologists prefer

the subclavian route but this should be avoided in thepresenceof thrombolysis or anticoagulation. Alternativesites should bechosen in this situation.

Pr ophylacti c therapies in the acute phase

Aspirin. Convincing evidence of the effectiveness ofaspirin was demonstrated by theI SIS-2trial[16], in whichit was shown that the benefits of aspirin and strepto-kinase were additive. In this trial of more than 17000patients, the first 160mg tablet of aspirin was chewed;subsequently one 160mg tablet was swallowed daily.The mortality in those receiving aspirin in ISIS-2 was94% compared with that of 118% in those receivingplacebo. It was effectiveboth in thosewho did andthosewho did not receive thrombolysis. In an overview of allthe aspirin trials[55], a 29% odds reduction in death wasobserved, with a vascular mortality of 117% in thecontrol population and 93% in those receivingaspirin representing 24 lives saved per 1000 patients

treated. There were also fewer non-fatal strokes andnon-fatal myocardial reinfarctions in thetreated group.There are few contra-indications to the use of

aspirin, but it should not begiven to thosewith a knownhypersensitivity, bleeding peptic ulcer, blood dyscrasia,or severe hepatic disease. Aspirin may occasionallytrigger bronchospasm in asthmatics. Unlike the situ-ation with thrombolysis, there is no clear evidence of arelationship between effectiveness and thetimefrom theonset of symptoms. Nonetheless, aspirin should begivento all patients with an acute coronary syndrome assoon as possible after thediagnosis is deemed probable.This represents about 8595% of those sustaining amyocardial infarction.

Anti -arrhythmic drugs. Although it has been demon-strated that lignocaine can reduce the incidence ofventricular fibrillation in the acute phase of myocardialinfarction[56,57], this drug significantly increases theriskof asystole[57]. A meta-analysis of 14 trials showed anon-significiantly higher mortality in lignocaine treatedpatientsthan in controls[58]. Theprophylactic useof thisdrug does not appear justified.

Beta-blockers. M any trials of intravenous beta-blockadehave been undertaken in the acute phase of myocardialinfarction, becauseof their potential to limit infarct size,

reduce theincidence of fatal arrhythmias, and to relievepain. T he16000 patient I SIS-1[59] study of intravenousatenolol revealed a significant (2P2 min.

Adrena line given durin g loop a pprox every 23 min.

Continue loops for as long as defibrillation is indicated.

After 3 loops consider:

an alkal is ing a gent

an a nt iarrhythmic agent .

Figure 1 European Resuscitation Council guidelines onthetreatment of ventricular fibrillation




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beta-blockade undertaken since the widespread use ofthrombolysis was a substudy of theTI M I-IIB[61] but thenumber of events was too small to allow conclusions tobedrawn. As discussed below, theuse of beta-blockadein the acute phase of infarction in many countries isextremely low. Thereis a good casefor thegreater useofan intravenous beta-blocker when there is tachycardia(in theabsenceof heartfailure), relativehypertension, orpain unresponsive to opioids. I t may be prudent to testthe patients response to this form of therapy by firstusing a short-acting preparation.

Nitrates. A meta-analysis of 10 trials of early intra-venous nitrate therapy conducted in 2041 patientsshowed a mortality reduction of about one-third[62].Each of thetrials was small and with only 329 deaths inall, the results although highly significant had wideconfidence limits. TheGISSI-3[63] trial also tested intra-venousnitratetherapy (followed by transdermal nitrate)in 19394 patients; no significant reduction in mortalitywas observed, but this finding must be viewed withcaution as 44% of the patients assigned to the controlgroup received intravenous nitrate. The ISIS-4 trial[64],

in which oral mononitratewas administered acutely andcontinued for one month, also failed to show a benefit.Furthermore, a benefit wasnot seen in theESPRIM trialof molsidomine[65], a nitric oxide donor. Again, how-ever, both in ISIS-4and ESPRI M , thefrequent early useof intravenous nitrates in the control group makesdeductions difficult. The routine use of nitrates in theinitial phaseof myocardial infarction has, therefore, notconvincingly been shown to be of value.

Calcium antagonists. A meta-analysis of trials involvingcalcium antagonistsearly in thecourseof acutemyocar-

dial infarction showed a non-significant adversetrend[66]. There is no case for using calcium antagonistsfor prophylactic purposes in the acute phase of myo-cardial infarction.

Angiotensin convert ing enzyme ( A CE) inhibitors. It isnow well established that ACE inhibitors should bestarted in thelater hospital period in patients who havean impaired ejection fraction or who have experiencedheart failure in theearly phase (see later). Recently, theGISSI-3[63], ISIS-4[64] and Chinese Study[67] have shownthat ACE inhibitors started on the first day reducemortality in the succeeding 46 weeks by a small butsignificant amount. The CON SENSUS II trial[68], how-ever, failed to show a benefit. Thismay havebeen duetothe play of chance, or the fact that treatment wasinitiated with an intravenous formulation. A systematicoverview of trials of ACE inhibitions early in acutemyocardial infarction indicated that this therapy wouldresult in 46 fewer deaths per 1000 patients treated[64].Although it is recognised that subgroup analysis ishazardous, it would seemprobablethat thistherapy wasespecially valuable in certain high risk groups, such as

those presenting with heart failure or with previousinfarction. Thebenefitsof ACE inhibitionin myocardialinfarction patients appear to be a class effect. Theregimensused in the trials of ACE inhibitors are shownin Table 3.

As discussed later, opinions differ as to whetherto administer ACE inhibitor therapy to all patients (forwhom it is not contraindicated) on thefirst day or startit in a more selected group of patients shortly there-after[69,70,71]. In the view of the Task Force, there arevalid arguments on both sides. Certainly, there shouldbea low threshold for usingtheseagentsearly if features

Table 3 Dosages in ACE i nhibitor trials

I nitial dosage Target dosage

CONSENSUS II [68] 1mg i.v. enalaprilat over 2h up to 20mg dailyenalapril followed by 25 mg b.d.

increasing to 20 mg, if tolerated

GISSI-3[63] 5mg initially up to 10 mg dailylisinopril

ISIS-4[64] 625mg initially, 125mg in 2h, up to 50mg b.d.captopril 25mg at 1012 h

CHINESE[67] 625 mg i nitially, up to 125 mg t.d.captopril 125 mg 2 h later if tolerated

SMILE[117] 75 mg initially, up to 30 mg b.d.zofenopril repeated after 12 h and

repeatedly doubled if tolerated

AIRE[116] 25 mg b.d. increased up to 5 mg b.d.ramipril to 5 mg b.d. if tolerated

SAVE[115] test of 625mg, increased if up to 50mg t.d.captopril tolerated to 25 mg t.d.

TR ACE[118] test of 05 mg up to 4 mg dailytrandolapril




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of heart failuredo not respond quickly to conventionalmeasures.

M agnesium. A meta-analysis of trials of magnesiumtherapy in acute myocardial infarction suggested a sig-nificant benefit[72,73], but the later large ISIS-4 trial[64]

did not support this. A lthough it has been argued thatthe magnesium regimen in ISIS-4 was not optimal[74],there does not at present seem enough evidence torecommend its routine use.

M anagement of specific types of infarction

M any patients present with symptoms suggestive ofrecent myocardial infarction, but without the ECGfeatures of ST elevation or bundle branch block whichwould qualify them for thrombolytic therapy. Somewillprogressto Q waveinfarction, andothersto non-Q wave

infarction; many will eventually beclassified asunstableangina. A sizeableproportion will beregarded ashavingstable angina and yet others will have a non-cardiacdiagnosis. Themanagement will depend on thedegreeofsuspicion of infarction. Thus, if there has been a pre-vious infarction, or there are definite ST and T wavechanges short of ST elevation or new Q waves, or ifthe symptoms or physical signs suggest that this is anacute coronary syndrome, the patient should be closelyobserved with repeated ECG recordings and enzymetests. In the absence of contra-indications, all suchpatients should be given aspirin and considered forheparin therapy and beta-blockade. Continuing chestpain should be treated with nitrates and, if severe,opioids. If pain persists or recurs in spite of this treat-ment, cor-onary angiography should beconsidered witha view to early intervention by angioplasty or surgery.

- A non-Q wave myocardial infarction is one with thecharacteristic clinical features and enzyme abnormali-ties, but without new Q waves in the ECG. Theincidence is reported as being from 20 to 40% of allinfarctions but may beincreasing in relation to Q waveinfarction[75]. This variability could be related to the useof reperfusion therapy and/or more sensitivetechniquesfor enzyme detection[75,76].

Hospital mortality is significantly less than in Qwave infarction. Conversely in the long term, highermortality and event rates arereported in non-Q infarctsafter hospital discharge, so that the mortality is similarat 35 years[75,76]. A higher incidenceof residual ischae-mia is a constant finding (50%90% more than in Qwave infarction)[76,77].

Risk markers.Initial and persistent ST depression, com-plications present in the acute phase, post-infarctionangina with ECG changes, early reinfarction, and theinability to perform a stress test, areall associated with

a higher mortality[78,79]. A symptom-limited exercisestress test should be performed as in Q wave infarc-tion, but thallium scintigraphy and stress echocardiog-raphy may be more sensitive and specific in detecting,quantifying, and localizing ischaemic myocardium inasymptomatic non-Q wave postinfarction patients[75].

M anagement. Whether evolving infarction results in Qwaves or ends asa non-Q wave infarction is establishedonly after a few days follow-up. Thus, at the time ofadmission to CCU no distinction can be made betweenthese two groups of patients. Thrombolytic therapy isparticularly indicated in patients with ST segment eleva-tion dueto extensiveischaemia resulting from occlusionof a coronary artery[16]. The ISIS-2[16] and GISSI [18]

trials demonstrated no decreasein mortality with throm-bolysis in patients with myocardial infarction and STdepression on admission; these patients have probablynot had a complete coronary occlusion. Recent datafrom TIM I II IB, confirmed no significant benefit inmortality, or reinfarction ratewith t-PA in non-Q wave

infarction[80]

.Antithrombotic therapy with oral aspirin andintravenousheparin reduces theincidenceof subsequentreinfarction or death[81,82]. Thrombolysis may preventthe development of Q waves in those who present withST elevation.

Two small trials have suggested that diltiazemreduces early but not the total incidence of reinfarc-tion;[83,84] further evidence is needed before this agentcan be recommended for this purpose. There are nospecific studies designed to demonstrate the effect ofbetablockers in non-Q AM I. Retrospective analysisof the non-Q subgroup in general trials has beeninconclusive[85].

An early invasive strategy systematic cor-onary angiography and revascularization


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clear lung fields, and raised jugular venous pressurein apatient with inferior myocardial infarction[88]. ST elev-ation in V4R is very suggestive of the diagnosis

[89]; thislead should certainly berecorded in all cases of shock, ifnot doneasa routine. Q waves and ST elevation in V13also suggest the diagnosis.

When right ventricular infarction can be impli-cated in hypotension or shock, it is important tomaintain right ventricular preload. It is desirable toavoid (if possible) vasodilator drugs such astheopioids,nitrates, diuretics and ACE inhibitors. Intravenousloading is effectivein many cases; initially, it should beadministered rapidly, for example at a rate of 200ml in10min. It may require121normal salinein thefirst fewhours, and 200ml . h1 thereafter. Careful haemo-dynamic monitoring should be instituted during intra-venousfluid loading. If cardiac output does not improveon this regimen, dobutamine should be given.

Right ventricular infarction is often complicatedby atrial fibrillation. This should becorrected promptlyas the atrial contribution to right ventricular filling is

important in this context. Likewise, if heart block devel-ops, dual chamber pacing should be undertaken. Therehas been some question of theeffectivenessof thrombo-lytic therapy in right ventricular infarction, but itcertainly seems appropriate in the hypotensive patient.Alternatively, direct angioplasty may result in rapidhaemodynamic improvement[90].

Diabetic patients who sustain a myocardial infarctionhavea high mortality. Strict attention to thecontrol ofhyperglycaemia with insulin has been claimed to reducelong-term mortality[91]. Diabetes is not a contra-

indication to thrombolysis, even in the presence ofretinopathy.

Management of the later in-hospitalcourse

M ost patients should rest in bed for thefirst 1224h, bywhich timeit will be apparent whether theinfarction isgoing to be complicated. In uncomplicated cases, thepatient can sit out of bed lateon thefirst day, beallowedto use a commode and undertake self-care and self-

feeding. Ambulation can start the next day and suchpatients can be walking up to 200m on the flat, andwalking up stairs within a few days. Those who haveexperienced heart failure, shock or serious arrhythmiasshould bekept in bed longer, and their physical activityincreased slowly, dependent upon their symptoms andthe extent of myocardial damage.

Thesecomplications arenow relatively uncommon afterinfarction, except in patients kept in bed because ofheart failure. I n such patients, they can beprevented by

heparin. When they occur they should be treated withheparin, followed by oral anticoagulation for 36months.

Echocardiography will reveal intraventricular thrombiin many cases, especially largeanterior infarctions. If thethrombi are mobile or protuberant, they should betreated initially with heparin and subsequently with oralanticoagulants for 36 months.

Acute pericarditis may complicate myocardial infarc-tion, givingriseto chest pain that maybemisinterpretedas recurrent infarction or angina. Thepain is, however,distinguished by its sharp nature, and its relationship toposture and respiration. The diagnosis may be con-firmed by a pericardial rub. If thepain is troublesome, itmay betreated by high doseoral or intravenous aspirin,non-steroidal anti-inflammatory agents, or steroids. Ahaemorrhagic effusion with tamponade is uncommon

and is particularly associated with anticoagulanttreatment. It can usually be recognised echocardio-graphically. Treatment is by pericardiocentesis ifhaemodynamic embarrassment occurs.

Ventricular tachycardia and ventricular fibrillation oc-curring on the first day carry only a small adverseprognosis, but when these arrhythmias develop later inthe course they are liable to recur and are associatedwith a high risk of death. Thisis partlydueto their usualassociation with severe myocardial damage; a carefulassessment of coronary anatomy and ventricular func-tion should always beundertaken. I f it is probablethatthe arrhythmia is induced by ischaemia, revasculariz-ation by angioplasty or surgery should beconsidered. Ifthis is unlikely, a variety of therapeutic approaches areavailable which are, as yet, inadequately researched.Theseincludetheuseof beta-blockers, amiodarone, andelectrophysiologically guided anti-arrhythmic therapy.In some cases, an implantable converter defibrillator isindicated.

- M ild angina occurring in those with a previous historyof the condition may respond satisfactorily to theusual medical treatment, but new, especially rest, angina

in the early post-infarction phase requires furtherinvestigation.The routine use of elective PTCA following

thrombolytic therapy has been compared with a con-servative approach in several randomized trials[9294]. I tcan be concluded that routine PTCA in the absence ofspontaneous or provocable ischaemia does not improveleft ventricular function or survival. In treating anginaor recurrent ischaemia, however, whether due to re-occlusion or to a residual stenosis, PTCA has a definiterole. It may also be of value in managing arrhythmiasassociated with persistent ischaemia. A lthough analyses




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from several trials haveidentified a patent infarct-relatedvessel as a marker for good long-term outcome, it hasnot been shown that late PTCA with the sole aim ofrestoring patency influences late events.

Coronary artery bypasssurgery maybeindicatedif symptoms are not controlled by other means or ifcoronary angiography demonstrates lesions, such asleft main stenosis or three vessel disease with poorleft ventricular function, for which surgery improvesprognosis[95].

Risk assessment, rehabilitation, andsecondary prevention

Risk assessment prior to discharge has theobjectives ofestimating prognosis, deciding which further investiga-tions are required, and assisting in devising the bestindividual therapeutic strategy for patients who survivethe acute event. This assessment depends partly onclinical data, including age, pre-existing risk factors,previous infarction, diabetes, haemodynamic status andarrhythmias during the acute phase, and partly onfunctional investigations and imaging.

Clinical risk stratification can beused to divide patientsinto high, intermediate and low risk categories. Thisclinical stratification is important because the yield ofinvestigations dependscritically on thepre-test probabil-ity of a positiveresult.

Evaluation of high risk cases.Patients at the highest riskarethose with persistent heart failure, severely impairedleft ventricular function, persistent or early appearanceof angina at rest or on minimal exertion, or recurrent

arrhythmias, and those unable to perform a pre-discharge exercise test[9699]. Such patients tend to beolder, to have multiple risk factors, and to have hadprevious infarcts. Left ventricular function should beevaluated by echocardiography and/or scintigraphy.Coronary angiography provides independent prognosticinformation and acts as a guide to further treatmentsuch as revascularization[100].

Evaluation of medium risk cases.Cases that areclinicallyat medium risk are likely to be older than 55 years,have had transient heart failure, have had a previousinfarction or have risk factors such as hypertension ordiabetes. These patients should be assessed for leftventricular dysfunction and for residual ischaemia. Thelatter may be assessed by exercise electrocardiography,myocardial perfusion scanning or stress echocardiogra-phy, depending on local availability. Patients withimpaired left ventricular function and/or inducible is-chaemia should be considered for angiography. Thisapproach to stratification is shown as a flow chart inFigure2.

Evaluati on of low r isk patients. Low risk patients areyounger (age


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the negative predictive accuracy for patients who cancomplete stage III of the standard Bruce protocol or itsequivalent withoutchest pain or ischaemic ECG changesis high[101]. In addition, the effect on patient morale ispositive, and the information is helpful in planningrehabilitation. There is no necessity to discontinuemedication before exercise testing.

Patients who fail to achievea satisfactory workload onexercisetesting, or who develop angina or electrocardio-graphicsignsof ischaemia ata mediumworkloadshouldbeconsidered for further evaluation in order to localizethesiteand quantify theamount of myocardiumat risk,as well as the extent of potentially viable myocardium.The choice between stress echocardiography and radio-isotopeperfusion scanningdependsupon theexperienceof the individual centre and the resources available.In competent hands, both these techniques are moresensitiveand specific than exercise electrocardiography.

Evaluation of cardiac impairment by echocardiographyor radionuclide ventriculography is helpful in assessingpatientswith no evidenceof cardiacfailure, particularlyif performed under conditions of stress, though leftventricular function is likely to bewell preserved in lowrisk cases.

Holter monitoring and electrophysiological studies areof value in the assessment of patients considered to beat high risk of arrhythmias. Heart rate variability, QTdispersion, baroreflex sensitivity, and late potentialshave all been found to be of prognostic value aftermyocardial infarction, but further clinical experience isneeded to establish whether they add substantially to themore conventional prognostic tests.

It is also important to measure metabolic risk markerssuch as total, LDL and H DL cholesterol, fasting tri-glyceride and plasma glucose in all patients.

Coronary angiography should be undertaken in theearly post-infarction period when there is:Angina that does not respond to pharmacological

therapyAngina or evidence of myocardial ischaemia at restExercise-induced angina or myocardial ischaemia at alow workload, or on Holter monitoring, when therehas been little or no increase in heart rate.Coronary angiography should be considered whenthere is:Angina or objective evidence of provocable myo-cardial ischaemia (in the absence of the featuresdescribed above)Postinfarction angina responding to pharmacologicaltherapy

Severe left ventricular dysfunctionComplex ventricular arrhythmia morethan 48h afterthe onset.

In selected cases, especially in younger individuals, cor-onary angiography can be considered for patients withan uncomplicated course to evaluate the success ofreperfusion, to identify those with extensive coronaryartery disease, and to facilitate early hospital dischargeand return to work.

Rehabilitation

Rehabilitation is aimed at restoring thepatient to as fulla life as possible, and must take into account physical,psychological and socio-economic factors. The processshould start assoon aspossibleafter hospital admission,and be continued in the succeeding weeks and months.Thedetailsof rehabilitation will notbediscussed here, asfull consideration of its principles and methodsaredealtwith in the reports of theWorking Group on Rehabili-

tation of the European Society of Cardiology[102]

.

Psychological and socio-economic aspects. Anxiety isalmost inevitable, both in patients and their associates,so that reassuranceand explanation of thenatureof theillness is of great importance and must be handledsensitively. It is also necessary to warn of the frequentoccurrence of depression and irritability that morefrequently occurs after return home. It must also berecognised that denial is common; while this may havea protective effect in the acute stage, it may makesubsequent acceptance of the diagnosis more difficult.

Thequestion of return of work and other activit-ies should be discussed prior to hospital discharge.

L if esty le advice.Thepossible causes of coronary diseaseshould be discussed with patients and their partnersduring hospitalization, and individualized advice on ahealthy diet, weight control, smoking and exercisegiven.

Physical activit y. A ll patients should be given advicewith regard to physical activity based upon their recov-ery from the heart attack, taking into account their age,their preinfarction level of activity, and their physicallimitations. Assessment is greatly aided by a pre-discharge exercise test, which not only provides usefulclinical information but can be reassuring to the over-

anxious patient. A meta-analysis of rehabilitation pro-grammes which included exercisesuggested a significantreduction in mortality[103].

Secondary prevention

Smoking.Although no randomized trials have beenundertaken, compelling evidence from observationalstudies shows that those who stop smoking have amortality in the succeeding years less than half that ofthose who continue to do so[104]. This is, therefore,




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potentially themost effectiveof all secondary preventionmeasures; much effort should be devoted to this end.M ost patients will not have smoked during the acutephase and the convalescent period is ideal for healthprofessionals to help smokers quit the habit. Resump-tion of smoking is common after return home andcontinued support and advice is needed during rehabili-tation. A randomized study has demonstrated theeffec-tiveness of a nurse-directed programme[105]: a smokingcessation protocol should beadopted by each hospital.

Diet and dietary supplements. There is little evidence onthe effectiveness of dietary treatment of postinfarctionpatients, but a weight reducing diet should beprescribedfor those who are overweight. All patients should beadvised to take a diet low in saturated fat and high infruit and vegetables. Onestudysuggeststhat takingfattyfish at least twicea week reduces therisk of reinfarctionanddeath[106]. Theroleof antioxidants in thepreventionof coronary disease has yet to be established.

Anti platelet and anticoagulant tr eatment. T he Anti-platelet Trialists Collaboration[55] meta-analysis demon-strated about a 25% reduction in reinfarction and deathin post-infarction patients. In thetrials analysed, aspirindosages ranged from 75 to 325mg daily. There is someevidence that the lower dosages are effective with fewerside-effects.

Clinical trials undertaken before the widespreaduse of aspirin showed that oral anticoagulantsareeffec-tive in preventing reinfarction and death in survivors ofmyocardial infarction[107,108]. Thepatients in these trialswere randomized at least two weeks after the indexinfarction. Therole of routineearly oral anticoagulationfollowing acute myocardial infarction is less clear andhas only recently been evaluated after thrombolytictherapy[29,109]. In such patients there is no clear benefitover antiplatelet therapy. Possibly, subsets of patients,e.g. those with left ventricular aneurysm, atrial fibrilla-tion or echographically proven left ventricular thrombusmight benefit from early oral anticoagulation, but largerandomized trials in this field arelacking. Theambulantuse of subcutaneous heparin may behelpful[110], but theresults should beconfirmed in morestudies.

Combined anticoagulant and antiplatelettherapy after myocardial infarction is currently beinginvestigated; the first results appear promising[111].

Beta-blockers. Several trials and meta-analyses havedemonstrated that beta-adrenoceptor blocking drugsreduce mortality and reinfarction by 2025% in thosewho have recovered from acute myocardial infarc-tion[60,85]. Positive trials have been conducted withpropranolol, metoprolol, timolol and acebutolol, butstudies with other beta-blockers, although not signifi-cant, are compatible with a comparable effect. About25% of patients have contra-indications to beta-blockade because of uncontrolled heart failure, respira-tory disease or other conditions. Of the remainder,perhapshalf can bedefined asof low risk[85,112], in whom

beta-blockadeexerts only a marginal benefit, bearing inmind the minor though sometimes troublesome side-effects. Opinion is divided as to whether beta-blockersshould beprescribed to all those for whom they are notcontra-indicated, or whether they should only be givento those at moderaterisk who havethemost to gain.

Calcium antagonists. Trials with verapamil[113] anddiltiazem[114] have suggested that they may preventreinfarction and death,but caution must be exercised inthepresenceof impaired ventricular function. They maybe appropriate when beta-blockers are contra-indicated(especially in obstructive airways disease).

Trials with dihydropyridines[66] have failed toshow a benefit in terms of improved prognosis aftermyocardial infarction; they should, therefore, only beprescribed for clear clinical indications, bearing in mindthe potentially adverse effects in those with poor leftventricular function.

Nitrates.There is no evidence that oral or transdermal

nitrates improve prognosis after myocardial infarc-tion, the ISIS-4[64] GISSI-3[63] trials failing to show abenefit at 46 weeks after the event. Nitrates, of course,continueto be first line therapy for angina pectoris.

A ngiotensin convert ing enzyme ( A CE ) inhibit ors.Severaltrials haveestablished that ACE inhibitors reduce mor-tality after acute myocardial infarction[115118]. In theSAVE trial[115] patients were entered a mean of 11 daysafter theacuteevent if they had an ejection fraction less40% on nuclear imaging, and if they were free ofmanifest ischaemia on an exercise test. No mortalitybenefit was seen in the first year, but there was a 19%reduction in thesucceeding35 yearsof follow-up (from246 to 204%). Fewer re-infarctions and less heartfailure were, however, seen even within the first year.

In the AI RE trial[116] patients were randomizedto ramipril a mean of 5 days after the onset of amyocardial infarction that was complicated by theclini-cal or radiological features of heart failure. At anaverage of 15 months later, the mortality was reducedfrom226% to 169% (a 27% reduction). In the TR ACEstudy[118], patients were randomized to trandolapril orplacebo a median of 4 days after infarction, if they hadleft ventricular dysfunction as demonstrated by a wallmotion index of 12 or less. At an average follow-up of108 weeks, themortality was 347% in thetreated group

and 423%in theplacebo group. Takingthethreestudiestogether, there is a strong case for administering ACEinhibitorsto patientswho haveexperienced heart failurein theacuteevent, even if no features of this persist, whohave an ejection fraction of less than 40%, or a wallmotion index of 12 or less, provided there are notcontra-indications.

As discussed above, there is a case for admin-istering ACE inhibitors to all patients with acuteinfarction from admission, provided there are nocontra-indications. Against such a policy is theincreasedincidence of hypotension and renal failure in those




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receiving A CE inhibitors in the acute stage, and thesmall benefit in those at relatively low risk, such aspatients with small inferior infarctions. With the veryearly use of ACE inhibitors, consideration should begiven to discontinuing these agents at 46 weeks if theclinical coursehas been uncomplicated and the ejectionfraction greater than 40%.

L ipid-lowering agents. The Scandinavian SimvastatinSurvival Study (4S)[119]clearly demonstrated thebenefitsof lipid-lowering in a population of 4444 anginal and/orpost-infarction patients with serum cholesterol levelsof 5580mmol . l1 (212308mg . dl1) after dietarymeasures had been tried. Patients were not entered intothe trial until 6 months after an acute infarction, anda relatively low risk group of patients was recruited.Overall mortality at a median of 54 years was reducedby 30% (from12 to 8%). This represented 33 lives savedper 1000 patients treated over this period. There weresubstantial reductions in coronary mortality, and in theneed for coronary bypass surgery. Patientsover 60 years

of age appeared to benefit asmuch as younger patients.Women benefited as far as major coronary events wereconcerned, but a statistically significant reduction indeath was not demonstrated; this may have been as aresult of therelatively small number of women recruited.

Lipid-lowering agents should, therefore, be pre-scribed for patients who correspond to those recruitedinto 4S, but controversy still exists as to how soontreatment should bestarted after theevent, and whetherthe criteria for treatment should be extended to thosewith lower lipid levels.

Logistics of care- Pati ent delay.The most critical time in an acute heartattack is thevery early phase, during which thepatient isoften in severepain and liableto cardiac arrest. Further-more, the earlier that some treatments, notably throm-bolysis, are administered, the greater the beneficialeffect. Y et, it is often an hour or more after the onsetbefore aid is requested. Sometimes this reflects the factthat the symptoms are not severe, or typical, or abruptin onset, but frequently immediate action is not takeneven when they are. It should be a normal part of thecare of patients with known ischaemic heart disease to

inform them and their partners of the symptoms of aheart attack and how to respond to it. It is less certainwhat should be the role of education of the generalpublic. Certainly, the public must be aware of how tocall the emergency services, but although they haveachieved some success, it is questionable whether publiceducation campaigns have had a significant impact onoutcome[120,121].

Public education in cardio-pulmonary resuscitation. Thetechniques of basic life support should be part of theschool curriculum. Those most likely to encounter

cardiac arrest while at work, such as the police andfire service personnel, should be proficient in cardio-pulmonary resuscitation.

T he ambulance service. The ambulance service has acritical role in the management of acute myocardialinfarction and cardiac arrest. The quality of the caregiven depends on the training of the staffconcerned. Atthe most simple level, all ambulance personnel shouldbe trained to recognise the symptoms of myocardialinfarction, administer oxygen and pain relief, and pro-vide basic life support. All emergency ambulancesshould be equipped with defibrillators and at least oneperson on board trained in advanced life support.Doctor-manned ambulances, available in only a fewcountries, can provide more advanced diagnostic andtherapeutic skills, including the authorisation to giveopioids and thrombolytic drugs. In some countries,suitably trained nurses undertake these functions.

It is desirable for ambulance staffto record anECG for diagnostic purposes and either interpret it or

transmit it so that it canbereviewed byexperienced staffin a coronary care unit or elsewhere. The recording ofan ECG prior to admission can greatly acceleratein-hospital management[122,123].

General practit ioners. I n some countries, general prac-titioners play a major role in the early care of myocar-dial infarction. In thesecountries, they areoften thefirstto becalled by patients. If they can respond quickly andhave been suitably trained, they can be very effective,because they may know the individual patient, recordandinterpret an ECG, beableto administer opioidsandthrombolytic drugs, and undertake defibrillation[123,124].In most areas, general practitioners are not so trained.In this circumstance, although it is desirable thatthey attend the patient without delay, they shouldimmediately call for an ambulance.

Admission procedures. The processing of patients oncethey arrivein hospital must bespeedy, particularly withregard to diagnosis and the administration of throm-bolysis, if indicated. In some hospitals, direct admissionto a coronary care unit may be the best option, butin most, patients are first delivered to an EmergencyDepartment. Delays here can be substantial; it is essen-tial that suitably qualified staffare available to assessand treat patients with suspected myocardial infarction

in this environment. Patients with clear-cut features ofmyocardial infarction, whose ECG demonstrate eitherST elevation or left bundle branch block, should enter afast-track system, in which thrombolysis is instituted inthe Emergency Department so that thedoor-to-needletime is no more than about 20min. Other cases mayrequire more detailed assessment which may be betterundertaken in the coronary care unit.

() ()All patientswith suspected myocardial infarction shouldinitially be assessed and cared for in a designated unit,

Guidelines on acute myocardial infarction 57



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where appropriately trained staffare constantly avail-able and where thenecessary equipment for monitoringand treatment areimmediately at hand. WheretheCCUis used, as it usually is, for triage, it is important thatsatisfactory arrangements exist for the rapid transfer toother wards of those not needing its highly specialisedfacilities.

Non-invasive monitoring. Electrocardiographic monitor-ing for arrhythmias should be started immediately inany patient suspected of having sustained an acutemyocardial infarction. T his should be continued for atleast 24h or until an alternative diagnosis has beenmade. Further ECG monitoring is dependent upon theperceived risk to the patient and upon the equipmentavailable. When a patient leaves the CCU, monitoringof rhythm may becontinued, if necessary, by telemetry.M ore prolonged monitoring is appropriate for thosewho have sustained heart failure, shock or seriousarrhythmias in the acute phase as the risk of furtherarrhythmias is high.

I nvasive monitor ing.All coronary careunits should havetheskills and equipment to undertake invasivemonitor-ing of the arterial and pulmonary artery pressures.Arterial pressure monitoring should be undertaken inpatients with cardiogenic shock. Balloon flotation cath-eters, such as the Swan-Ganz catheter, are of value forthe assessment and care of patients with low cardiacoutput. They permit measurement of right atrial, pulmo-nary artery and pulmonary wedgepressures, and cardiacoutput. Balloon flotation catheters are indicated in thepresenceof cardiogenic shock, progressive heart failure,and suspected ventricular septal defect or papillarymuscle dysfunction.

The current use of therapies tested by

clinical trials

The results of clinical trials have often not been imple-mented in practice and treatments which have beenshown to be of little or no value continue to be usedwidely. It has been difficult to obtain reliabledataon theutilization of therapies in myocardial infarction, exceptfrom clinical trials, which may not be truly representa-tive of current practice. The European Secondary Pre-vention Study Group have recently reported[125,126] on

the utilization of drugs in samples of 200520 repre-sentative acute myocardial infarction patients from 11countries. Thrombolytic therapy was given to an aver-age of 35% of patients (range 13 to 52%). The use ofintravenous beta-blockade varied from 0554% (aver-age 13%). Oral beta-blockade at discharge varied from3381% (average 52%). These data emphasize the needboth for continuing medical education and for ongoingaudit to ensure the implementation of therapeutic ad-vances. Centres which participatein multicentre clinicaltrials are more likely to implement evidence-basedchanges in clinical practice[127].

Recommendations

Patients.Patients with a suspected heart attack have aright to expect prompt diagnosis, pain relief, resusci-tation and, if indicated, reperfusion treatment.

Patients with suspected or confirmed myocardialinfarction should be cared for by staff trained andexperienced in modern coronary care. They should haveaccess to advanced methods of diagnosis and treatmenteither at the initial place of management or followingtransfer to a specialist unit.

They should have appropriatefacilities for post-discharge follow-up, rehabilitation and secondaryprevention.

They and their associates should be informed ofhow to recognise and respond to a further heart attack.

Cardiologists. Cardiologists, in association with emer-gency care physicians and health authorities, shouldensure that an optimal system for the care of heartattack patients is operative in their area. This should

includetheappropriatetraining of ambulancepersonneland first-line doctors, efficient arrangements for thediagnosis and treatment of suspected myocardial infarc-tions in the Emergency Department, and protocols forthe prompt administration of thrombolytic treatment.

Cardiologists, in association, with anaesthetistsand other relevant specialists, should ensure that medi-cal and paramedical hospital staff are competent inresuscitation techniques.

Registersshould bekept of thetimefromthecallfor care and the administration of thrombolysis (call-to-needle time) and that from hospital admission tothrombolysis (door-to-needle time). Theformer shouldbe no longer than 90min and for fast track patientswith clear indications for thrombolysis, the door-to-needle time should not exceed 20min.

Registers should also be kept of the proportionof patients with definite myocardial infarction admittedwithin 12h of theonset of symptoms with ST elevationor bundle branch block who receive thrombolysis. Thisproportion should probably bein excess of 90%.

PTCA may be regarded as a viable and cost-effective alternative to thrombolytic therapy when theappropriateskills and facilities areavailable. Theresultsof PTCA should berecorded in a national register.

A rehabilitation programme should be madeavailable for all patients, tailored to their individual

needs. There should bea policy for smoking cessation.This must consist of a continuing programme run byhealth professionals that not only encourages patientstostop, but endeavours to maintain cessation.

Records should bekept of secondary preventiontherapy prescribed to survivors of definite myocardialinfarction. Suggested minimumtarget figures at thetimeof discharge are for aspirin >85%, beta-blockers >35%and ACE inhibitors >20%.

All patients should have their lipids measured,preferably on the day of admission. Those with raised




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lipidsshould first receivedietary advice. Should this failto reduce raised lipid levels sufficiently, considerationshould begiven to lipid-lowering drugs, accordingto thecriteria of theScandinavian Simvastatin Survival Study.

General practitioners.When general practitioners arethefirst point of contact for cases of suspected myocardialinfarction, they must either be able to respond immedi-ately or makeprovision for theemergency services to doso, or (preferably) both.

If general practitioners can respond quicklyand are appropriately trained and equipped, they canprovide defibrillation and thrombolysis effectively.

They should be involved in the co-ordinatedlocal programme for the management of cardiacemergencies.

They should seepatientsassoon as possibleafterdischarge from hospital, ensure that their rehabilitationis properly organised, and oversee the appropriatesecondary prevention measures.

H ealth authoriti es. Health authorities should encouragethe training of the public in basic cardiopulmonaryresuscitation techniques and theambulancepersonnel inbasic and advanced life support.

They should ensure that an optimal system ofcare is available for patients suspected of sustainingcardiacarrest or myocardial infarction, byco-ordinatingthe activities of the ambulance service, general practi-tioners, and the hospital service.

They should ensure that Emergency Depart-ments have appropriate protocols for the promptmanagement of patients with suspected myocardial in-farction, and that there are appropriately trained staffavailable at all times.

They should provide sufficient beds for theintensive care of patients with myocardial infarction.Physicianswith a formal trainingin cardiology must beavailable.

They should make provision for the rehabili-tation of patients discharged from hospital aftermyocardial infarction.

They should ensurethat facilities areavailableintheir own hospital or district for the advanced investi-gation and treatment of patientswith thecomplicationsof myocardial infarction or, if not available locally,arrangements have been made with tertiary centreselsewhere.

Procedure of the T ask Force. The Task Force on theM anagement of Acute M yocardial Infarction was cre-ated by the Committee for Scientific and Clinical Initia-tives of theEuropean Society of Cardiology in February1995 and asked to report to the Congress of the Societyin August 1995. The members of the Task Force wereProf. D. G. J ulian (Chairman) U.K ., Prof. J .-P. Boissel(France), Prof. D . P. D e Bono (U.K .), Prof. K . A. A.Fox (U.K.), Dr J Heikkila (Finland), D r L. Lopez-Bescos (Spain), Prof. K .-L. Neuhaus (Germany),Prof. R. Schrder (Germany) Prof. P. Sleight (U .K .),

Prof. G. Specchia (Italy), Drs A . Sigurdsson and K .Swedberg (Sweden), Prof. M . Turina, Dr M . Genoni(Switzerland), Prof. F. W. A. Verheugt (TheNetherlands), Prof. F. van de Werf (Belgium), Dr F.Zijlstra (TheNetherlands).

Individual members were invited to submit draftpapers in their area of expertise and these were firstdiscussed at a meeting in London on 15 and 16 M ay.After several revisions, and consultation with membersof theCommittee, the members met again on 4 J uly inAmsterdam. The document was redrafted and widelycirculated prior to submission of the final document totheCommittee for its approval.

Invaluable assistancein processing thedocumentwas provided by M rs W. Thieme. The guidelines weredeveloped without any involvement of thepharmaceuti-cal companies that provided financial support of itsactivities.

Financial support. The Task Force wishes to express itsappreciation of thefinancial support provided by Astra

Hssle AB, Behringwerke AG, Institut de RecherchesInternationales Servier, K noll AG, Laboratoires Searle,M erck, Sharp and Dohme, and Pfizer Ltd.

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