THE LANCET

The challenge of acute coronary syndromes

Maarten L Simoons, Eric Boersma, Coen van der Zwaan, Jaap W Deckers

Introduction Risk indicators Assessment Decision

Acute coronary syndromes (ACS) pose multiple
Prehospital
challenges to physicians, cardiologists, internists, and Age Low probability ACS No admission
emergency department physicians, as well as to general History and
practitioners. General practitioners are responsible for current symptoms Not low probability ACS Hospital admission
ECG
early recognition of ACS among patients with chest ST elevation (MI) Prehospitalthrombolysis
discomfort and identification of patients who require Hospital admission
hospital admission; cardiologists and other specialists Age Low risk ACS Direct discharge
prescribe initial and subsequent medical therapy and History and
select patients for immediate, early, or elective current symptoms Moderate risk ACS Observation (pre CCU),ASA,
Heart failure signs heparin, ~-blockers, NTG
revascularisation by percutaneous techniques (balloon Troponin High risk ACS
angioplasty, stent) or bypass surgery. A systematic ECG Raised troponin T/I Add lib/Ilia receptor blockers,
approach may guide the physicians to meet these ST depression consider angiogram, PTCA,CABG
challenges (table). ST elevation (MI) Tailored reperfusion therapy
The term ACS encompasses a spectrum of patients who Hospital coarse
present with chest discomfort or other symptoms caused ECG infarct failure reperfusion Consider rescue PTCA
by myocardial ischaemia. T h e unification of ECG-ischaemic monitoring
these manifestations of coronary artery disease under Recurrent ischaemia Consider angiography, PTDA,DAB6
a single term reflects the understanding that these Predischarge
Stress test Low risk Early discharge
are caused by a similar pathophysiology, characterised (ECG, echo, scintigraphy)
by erosion, fissuring, or rupture of a pre-existing plaque, Heart failure Consider angiography,PTCA,CABG
leading to intravascular thrombosis and impaired Ischaemia
myocardial blood supply? T h e presence or absence Postdlscharge Recurrent symptoms
of mechanical obstruction by the plaque and its Stop Smoking
Prudent diet
contents, the amount and extent of associated thrombus ASA, statins
formation, and the degree of collateral circulation I~-blockers, ACE inhibitors
determine the outcome of patients, particularly whether OPR training of relatives
Readmission
myocardial ischaemia recovers fully or results in
minor or major myocardial necrosis. The common Systematic approach to ACS
Ml=myocardial infarction; CCU=coronarycare unit; ASA=aspirin; NTG=nitroglycerin;
pathophysiology of different clinical presentations of ACS PTCA=percutaneous coronary angioplasty; CABG=coronaryartery bypass grafting;
logically requires a similar therapeutic approach. In echo=echocardiogram; OAR=cardiopulmonary resuscitation.
the 1970s, attention focused on management of life-
threatening arrhythmias. Coronary care units were Triage o f p a t i e n t s w i t h c h e s t pain
introduced to detect and treat such arrhythmias by In patients with sudden or prolonged chest discomfort,
pacemakers (A-V block) or defibrillation (ventricular diagnosis of suspected evolving myocardial infarction or
fibrillation).2-~ Defibrillators were also introduced in unstable angina resides upon patients' history and the
ambulances. Antiarrhythmic drugs were also introduced characteristics of the chest pain, while physical
to prevent ventricular fibrillation. Subsequently, attention examination is often not informative. Certainty about the
shifted to measures to reduce myocardial oxygen diagnosis can be obtained only from the evaluation of the
consumption with [3-blockers, nitrates, and calcium electrocardiogram (ECG) and from biochemical markers
antagonists.' These agents prevented progression to of myocardial necrosis upon presentation and their
myocardial infarction in patients with unstable angina, evolution in subsequent hours and days. In patients with
and improved outcome in selected patients with evolving evolving myocardial infarction, early mortality is high, and
infarction." In the past 10 years, reperfusion therapy has immediate E C G monitoring, as well as immediate
been introduced, supported by intensive antithrombotic reperfusion therapy, are mandatory. It has been customary
and anticoagulant therapy. The value of reperfusion for over 25 years to admit all patients with suspected
therapy with coronary occlusion (evolving infarction) by myocardial infarction to a hospital coronary care unit.
thrombolytic therapy or direct angioplasty has b e e n well Similarly, patients with suspected unstable angina are
established. 9-n However, the indications for, and optimum admitted since they are at risk of progressing to
timing of, percutaneous or surgical coronary intervention myocardial infarction. This strategy results in hospital
in the spectrum of patients with unstable angina are still admission of a large number of patients who, in
debated. H retrospect, are not at immediate risk. Therefore, special
units have been introduced with a low threshold for
Lancet $ 9 9 9 ; 3 5 3 (suppl II): 1 - 4 admission and with facilities for E C G arrhythmia
Thoraxcenter, Bd 434, Academisch ZiekenhuisDijkzigt, monitoring and, more recently, computer-assisted ST-
3015 GD, Rotterdam, Netherlands(M L Simeons Me, E Boersma Me, segment ischaemia monitoring, and for rapid assessment
C van der Zwaan MD,J W Deckers MD) of cardiac status. This approach was developed in
Correspondence to: Prof Maarten L Simoons Amsterdam in 1972 and a special unit, called "Eerste
(e-mail: simoons@tch.fgg.eur.nl) Hart Hulp" (Cardiac Emergency Unit) was opened in

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THE LANCET
downtown Amsterdam in 1978 and is still operational
at the Academic Medical C e n t r e 2 z Similar units were
created in other hospitals in Netherlands. These early
precoronary care units provided E C G arrhythmia
monitoring, sequential measurements of myocardial
proteins (creatinine kinase [CK], CK-MB) and functional
assessment of myocardial perfusion, 13 although the latter
method may be too costly for routine use. Introduction
of precoronary care units did reduce the proportion of
patients not at immediate risk who were nevertheless
admitted to the more costly coronary care unit and
facilitated early discharge of low-risk patients. 1~14 More
recently, similar chest-pain units have been opened in the
USA) ~
The diagnosis of evolving myocardial infarction or
of unstable angina is surrounded by uncertainty: a
decision not to admit a given patient may, in retrospect, be
questioned. Yet, admission and clinical assessment of all
patients with vague, non-specific symptoms would be
an unnecessary overkill. Simple algorithms may assist the
general practitioner as well as the physician in a hospital
emergency department in such decisions. Key elements
for such decision are the history of a patient, the character
and duration of chest-pain, and, particularly, the ECG.
A unique approach has been developed in Rotterdam,
where the ambulances are equipped with computerised
diagnostic E C G systems. The E C G interpretation is
provided on site to the general practitioners, who are
encouraged to reconsider whether a particular patient
should be admitted to hospital if symptoms have resolved
and the E C G is normal26 Of the first 121 patients who
were initially considered for hospital admission, but in
whom that decision was reversed upon analysis of the
E C G taken at home and provided by the ambulance
system, ten (8%) had a small infarction based on
subsequent systematic analysis of myocardial enzymes. All
recovered uneventfully. It was decided that the small risk
of a false-negative diagnosis was acceptable ~6 and the
limited risk of early discharge from a precoronary care
unit. ~ 4
Prehospital thrombolytic therapy
Equipment for E C G diagnosis, in addition to E C G
arrhythmia monitoring, was introduced for early
recognition of myocardial infarction in order to enable
immediate prehospital reperfusi0n therapy. 1~,~ The
benefits of such early prehospital fibrinolytic therapy
have been established, and are of similar magnitude
to the benefits of direct percutaneous transluminal
coronary angioplasty compared with inhospital
fibrinolysis--about 20 additional survivors of 1000
treated. ~9~2More widespread use of prehospital diagnosis
and treatment of myocardial infarction should be
encouraged. Furthermore, prehospital E C G diagnosis
may help to select patients for direct coronary angioplasty
when such treatment is available. Decisions at the
patient's home or elsewhere outside hospital have to be
taken rapidly, usually by physicians or ambulance nurses
with less experience than a hospital-based cardiologist.
Yet, the benefits of immediate prehospital treatment
outweigh the risk associated with a false-positive
diagnosis.
Tailored reperfusion therapy
Immediate reperfusion therapy is indicated in all patients
with symptoms suggestive of evolving myocardial
su2
intarction with a duration of less than 12 h and with
persistent ST-segment elevation or new bundle branch
10~11 . . . .
block. Different strategies may be chosen, Including
percutaneous transluminal coronary angioplasty (PTCA),
with or without stenting, and intravenous administration
of alteplase (accelerated regimen), reteplase, strep-
tokinase, or other fibrinolytics. A rescue P T C A procedure
may be offered to patients with apparent reperfusion after
intravenous thrombolysis, xl As in many other fields of
medicine, efficacy and costs of these different strategies
are proportionally related, with high direct costs for the
most effective treatment regimen--direct PTCA. Since
facilities are often limited, a physician has to choose the
most appropriate therapy within budgetary constraints.
Again, a systematic assessment of the expected benefit
expressed as "life-years saved" by each mode of therapy
as well as assessment of the risks of such therapy,
particularly the risk of intracranial )aaemorrhage with
thrombolytic therapy, 22 may guide physicians in their
choice of treatment for individual patients. 23'z4
Management of ACS without persistent
ST-segment elevation
Patients with ACS without persistent ST-segment
elevation, or new bundle branch block, usually have severe
coronary artery stenosis without total occlusion.
Immediate thrombolytic therapy in such patients is not
beneficial and should be avoided. The appropriate therapy
includes aspirin, unfractionated or low-molecular-weight
heparin, nitrates, and B-blockers. Platelet glycoprotein
IIb/IIIa receptor blockers have been shown to reduce the
risk of progression to myocardial infarction or death in
these patients. 2s'26 Systematic risk assessment may help
to select the optimum regimen for each patient, and
to identify those in whom early revascularisation by
P T C A or bypass surgery may be offered. Useful models
for risk assessment have been developed from the
G U S T O IIb and P U R S U I T databases. 2~,2~ Risk factors
associated with development of myocardial infarction
or death include advanced age, biochemical markers of
myocardial necrosis at enrolment, a recent history of
severe angina (Canadian Cardiac Society Class III or IV),
and ST-segment depression on the E C G at presentation.
In the larger trials, measurement of CK-MB or total C K
was recorded as a marker of myocardial necrosis at
enrolment. Other smaller studies, however, indicate that
measurement of cardiac troponin T or troponin I has
a higher predictive value for the identification of patients
at low risk of new life-threatening events. 29 In patients
at high risk of such events, for example, with a risk greater
than 5% in 30 days, angiography and coronary
revascularisation should be considered, z~ Patients at very
low risk (<1% at 30 days) are characterised by younger
age, absence of previous coronary artery disease, troponin
concentrations within the normal range, and absence
of ST-segment depression. Such patients are candidates
for early hospital discharge. In the intermediate group
(risk between 1% and 5%) close monitoring for recurrent
ischaemia and an early stress test may help to select
those who require additional revascularisation and those
who can be managed medically,z9,3In patients selected for
coronary angio-plasty, with or without a stent, a
glycoprotein IIb/IIIa receptor blocker should be continued
until after the procedure, because these drugs offer
significant protection from thrombotic events at the time
of the angioplasty,z~'z6
ACS 353 June 1999

Predischarge assessment
Before hospital discharge of patients admitted with ACS,
systematic risk assessment is required to decide upon the
optimum therapy in each individual. Specific attention
should be paid to left-ventricular function and to the
presence or absence of myocardial ischaemia.
Impaired left-ventricular function can be inferred by
measurement of myocardial damage if an infarct has
occurred (infarct size) and by measurement of residual
left-ventricular function (echocardiography, radionuclide
angiography, or left ventriculogram), or by assessment
of exercise capacity and the haemodynamic response
to exercise. 3t In patients with impaired left-ventricular
function, treatment with inhibitors of angiotensin-
converting enzyme (ACE) is warranted to improve long-
term outcome. 32
The presence or absence of inducible myocardial
ischaemia can be assessed by conventional stress testing
with 12-lead ECG, 32 by stress perfusion imaging, or by
stress echocardiography. Patients with recurrent angina,
those with spontaneous silent ischaemia, as well as
patients with stress-induced myocardial ischaemia should
be considered for coronary angiography and P T C A or
coronary bypass surgery as appropriate.
Important variations have been reported in length of
hospital stay after myocardial infarction or unstable
angina. These are probably related to local custom as
much as to true medical need. Early analysis of residual
left-ventricular function, myocardial ischaemia, and, in
some patients, coronary anatomy, may help to avoid
prolonged hospital stay in most patients without heart
failure or major arrhythmias. In particular, for patients in
whom coronary anatomy is known and who have had
PTCA, early discharge is usually appropriate.
Postdischarge management
In common with all patients with vascular disease,
treatment with aspirin and statins should be considered
after ACS, to reduce subsequent mortality and further to
retard progression of coronary disease, s3 Smoking should
be discouraged. Prolonged treatment with f3-blockers,
ACE inhibitors, or both should be considered in addition
to treatment for any residual symptoms. Patients with
signs of myocardial damage during admission, whether
spontaneous or associated with revascularisation
procedures, are at increased risk of recurrent coronary
thrombosis and should be instructed specifically to seek
help for new episodes of prolonged chest pain. 34
Conclusion
The whole spectrum of ACS has been investigated
thoroughly in recent decades. Such investigations have
resulted in indepth knowledge of the pathophysiology and
in extensive experience with different treatment methods
in large clinical trials. Additional data and expert insight
are presented by different contributions in this Lancet
supplement. The time has come to apply this knowledge
in a systematic manner in everyday clinical practice.
Simple decision-support systems as discussed above may
help the physician to select the best options for individual
patients.
References
1 Theroux P, Fusters V. Acute coronary syndromes. Unstable angina and
n o n - Q wave myocardial infarction. Clinical cardiology: new frontiers.
Circulation 1998; 9 7 : 1 1 9 5 206.
2 Day HW. An intensive coronary care area. Dis Chest 1963; 44: 423-27.
ACS 353 June 1999
THE LANCET
Brown K W G , McMillan RL, Borbath N, et al. C o r o n a r y care unit, an
intensive care centre for acute myocardial infarction. Lancet 1963; i:
349-52.
L o w n B, Fakhro A M , H o o d W B , T h o r n GW. The coronary care unit;
new perspectives a n d directions. JAMA 1967; 199: 188-98.
Bloom BS, Peterson OL. End results, cost and productivity of
coronary care units. N E n g l J M e d 1973; 2 8 8 : 7 2 78.
C o b b LA, B a u m RS, Alvarez III H , SchafferWA. Resuscitation from
out of hospital ventricular fibrillation: 4 year follow up. Circulation
1975; 51/52 (suppl III): 223-28.
Simoons M L , Serruys PW, Fopretti P, B r a n d M vd, Hugenholtz PG.
Practical guidelines for treatment with beta blockers and nitrates in
patients with acute myocardial infarction. Eur HeartJ 1983; 4:
129-35.
H I N T Research Group. Early treatment of unstable angina in the
coronary care unit: a randomised, double blind, placebo controlled
comparison of recurrent ischaemia in patients treated with nifedipine
or metoprolol or both. BrHeartI 1986; 5 6 : 4 0 0 13.
Simoons ML, Serruys PW, Brand M vd, et al. Improved survival after
early thrombolysis in acute myocardial infarction. A randomized trial
conducted by the Interuniversity Cardiology Institute in the
Netherlands. Lancet 1985; ii: 578 82.
10 Fibrinolytic T h e r a p y Trialists' (FTT) Collaborative Group.
Indications for fibrinolytic therapy in suspected acute myocardial
infarction: collaborative overview of early mortality and major
morbidity results from all randomised trials of more than 1000
patients. Lancet 1994; 3 4 3 : 3 1 1 - 2 2 .
11 T h e Reperfusion T h e r a p y Consensus Group. Factors that determine
efficacy and applicability for reperfusion therapy in clinical practice: a
search for consensus. EurHeartJ 1997; 18: 1371-81.
12 Durrer D, Lie KI,Wieken L R van der, et al. Results of a 24 h o u r day
out-patient facility for acute cardiac diseases (Eerste H a r t Hulp) in
Amsterdam. Proc Neth Acad Science 1979; 507-26.
13 Wackers FIT, Schoot JB van der, Busemarm E-Sokolo, et al.
Noninvasive visualization of acute myocardial infarction in m a n with
Thallium-201. Br HeartJ 1975; 37: 741.
14 Fineberg HV, Scaddem D, G o l d m a n L. Care of patients with a low
probability of acute myocardial infarction. Cost effectiveness of
alternatives to coronary care unit admission. N E n g l J M e d 1984; 310:
1301 07.
15 Roberts RR, Zelenski RJ, Mensah EK, et al. Costs of an emergency
department-based accelerated diagnostic protocol vs hospitalization
in patients with chest pain: a randomized controlled trial. JAMA
1997; 278 (20): 1670-76.
16 Grijseels E W M , Deckers JW, Hoes AW, et al. Prehospital triage of
patients with suspected acute myocardial infarction. Eur HeartJ
1995; 16: 325-32.
17 Bouten MJM, Simoons ML, H a r t m a n JAM, Van Miltenburg AIM,
Van der Does E, Pool J, Prehospital thrombolysis with alteplase
(rtPA) in acute myocardial infarction. EurHeartJ 1992; 13: 9 2 5 - 3 1 .
18 Aufderheide TP, Kereiakes DJ, Weaver WD, Gibler WB,
Simoons M L Planning, implementation, and process monitoring for
prehospital 12-lead E C G diagnostic programs. Prehosp Disaster Med
1996; 11 (3): 162-71.
19 Boersma E, Maas ACP, Deckers JW, Simoons ML. Early
thrombolytic treatment in acute myocardial infarction: reappraisal of
the golden hour. Lancet 1996; 3 4 8 : 7 7 1 - 7 5 .
20 T h e European Myocardial Infarction Project Group. Pre-hospital
thrombolytic therapy in patients with suspected acute myocardial
infarction. N E n g l J M e d 1993; 329: 383-89.
21 Boersma H, Haas ACP, Grijseels EWN, Deckers JW, H a r t m a n JAM,
Simoons ML. Benefits and risks of possible prehospitat thrombolysis
strategies--the role of the electrocardiogram. Cardiologie 1998; 5:
562-68.
22 Simoons M L , Maggioni AP, Knatterud G, et al. Individual risk
assessment for intracranial haemorrhage during thrombolytic therapy.
Lancet 1993; 3 4 2 : 1 5 2 3 528.
23 Simoons M L , Arnold AER. Tailored thrombolytic therapy. A
perspective. Circulation 1993; 88: 2556-64.
24 Boersma E, Steyerberg EW, Vlugt van der MJ, Simoons ML.
Reperfusion therapy for acute myocardial infarction: which strategy
for which patients? Drugs 1998; 56 (1): 31-48.
25 K o n g DE, Califf RM, Miller DP, et al. Clinical outcomes of
therapeutic agents that block the platelet glycoprotein IIb/IIIa
integrin in ischaemic heart disease. Circulation 1998; 98: 2829-35.
26 Ronner E, D y k u n Y, Brand M J B M van den, Wieken L R van der,
Simoons ML. Platelet glycoprotein IIb/IIIa receptor antagonists. An
asset for treatment of unstable coronary syndromes and coronary
intervention. Eur Heart~ 1998; 19: 1608-16.
27 Lee KL, Woodlief L H , Topoi EJ, et al, for the G U S T O investigators.
Predictors of 30 day mortality in the era of reperfusion for acute
myocardial infarction. Results from an international trial of 41 021
patients. Circulation 1995; 9 1 : 1 6 5 9 68.
su3
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28 Holmvang L, Luscher MS, Clemmensen P, Thygesen K, Grande P.
Very early risk stratification using combined E C G and biochemical
assessment in patients with unstable coronary artery disease (a
thrombin inhibition in myocardial ischaemia [TRIM] substudy).
Circulation 1998; 98: 2004-09.
29 Geleijnse ML~ Elhandy A~ Kasprzak JD, et al. Safety and prognostic
value of early dobutamine-atropine stress echocardiography in patients
with spontaneous chest pain and a nondiagnostic electrocardiogram. J
Am Coil Cardio11998; 11: 606-11.
30 Armstrong PW, FuY~ ChangWC, et al. Acute coronary syndromes in
the GUSTO-IIb trial prognostic insights and impact of recurrent
ischaemia. Ciculation 1998; 98: 1860-68.
31 Task Force of theWorking Group on Exercise Physiology,
s~i4
Physiopathology and Electrocardiology. Eurff Heart 1993; 14: 969-88.
32 TheTask Force on the management of acute myocardial infarction of
the European Society of Cardiology. Acute myocardial infarction:
pre-hospital and in-hospital management. Bur HeartJ 1996; 17:
43-63.
33 Wood D, Backer G de, Faergeman O, Graham I, Manicia (3,
Pyorala K. Prevention of coronary heart disease in clinical practice.
Recommendations of the Second Joint Task Force of European and
other Societies on Coronary Prevention. Bur Heart J 1998; 19:
1434-503.
34 Simoons ML~ Brand M van den, IAncoffM, et al. Minimal myocardial
damage during coronary intervention is associated with impaired
outcome. Eur Heartff (in press).
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