A Textbook of Clinical Pharmacology and Therapeutics

MANAGEMENT OFUNSTABLECORONARYDISEASE 199

Infarct limitation

In centres where immediate access is available to the cardiac
catheterization laboratory, the treatment of choice for limita-
tion of infarct size and severity is generally considered to be
primary angioplasty. However, at the present time, many hos-
pitals do not have such immediate access available, and in such
cases, since prevention of death and other serious complica-
tions is directly related to the speed with which opening of
the infarct-related artery can be achieved, antithrombotic/
fibrinolytic treatment should be instituted. Aspirinand throm-
bolytic therapy both reduce infarct size and improve survival –
each to a similar extent. Examples of thrombolytic drugs
commonly used are streptokinase,alteplase(also known as
recombinant tissue plasminogen activator, or rtPA), reteplase
andtenecteplase. Their beneficial effects are similar to one
another and additive with aspirin. Early fears about toxicity of
the combination proved unfounded, so they are used together.
Heparinor, more commonly low-molecular-weight heparin
administered subcutaneously, is needed to maintain patency of
a vessel opened by aspirinplus thrombolysis when alteplase,
reteplaseortenecteplaseare used; this is not the case, how-
ever, for streptokinase. Recent evidence suggests that the
additional use of clopidogrelin the early course of myocardial
infarction improves outcome further, over and above the bene-
fit seen with aspirinand thrombolysis or primary angioplasty.
Haemodynamic treatment has less impact than opening of
the infarct-related artery, but is also potentially important. The
intravenous use of β-blockers within the first few hours of

infarction has a modest short-term benefit. The International

Study of Infarct Survival (ISIS-1) (in patients who did not

receive the thrombolytic treatment or angioplasty which is

now standard) showed that the seven-day mortality in

patients treated early with intravenous atenolol was 3.7%,

compared to 4.3% in controls. This small absolute benefit was

not maintained (there were more deaths in the atenololgroup

than in the control group at one year) and does not warrant

routine use of β-blockers for this indication (as opposed to

their use in secondary prevention, five days or more after

acute infarction, which is discussed below). A rationale has

been developed for the use of angiotensin-converting enzyme

inhibitors (ACEI) in acute myocardial infarction, in terms of

possible improvements in cardiac work load and prevention

of deleterious cardiac remodelling. Trials with ACEI have

almost universally been positive in this context, showing bene-

fit in terms of mortality, haemodynamics and morbidity/

hospitalizations from heart failure in patients with evidence of

left ventricular dysfunction (e.g. on echocardiography) or of

clinically evident heart failure post-myocardial infarction.

Moreover, the magnitude of this benefit from ACEI treatment

increases with increasing ventricular dysfunction, whilst there

is little or no evidence of benefit in patients with normal left

ventricular ejection post-infarct. Examples of ACEI commonly

used in this context are enalapril,lisinopril,trandolapriland

ramipril. Moreover, recent trial evidence (e.g. from the

VALIANT study, using valsartan) suggests that angiotensin

receptor blockade may be a useful alternative to ACEI in

Persistent ST

segment elevation

No persistent

ST segment elevation

Clinical suspicion of ACS

Physical examination

ECG monitoring, Blood samples

ASA. LMW heparin

Clopidogrel*, beta-blockers, Nitrates

Undetermined

diagnosis

Thrombolysis ASA

PCI

High risk

Gp2b/3a

Coronary angiography

PCI CABG or medical management

depending upon clinical and

angiographic features

Low risk

Positive

Second troponin measurement

Twice negative

Stress test

Coronary angiography

*Omit clopidogrel if the patient is likely to go to CABG within 5 days

Figure 29.3:Recommended strategy for

management of acute coronary syndrome.

ASA, acetylsalicylic acid (aspirin); LMW

heparin, low-molecular-weight heparin.

(Adapted from the European Society of

Cardiology guidelines, 2002).