A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

MANAGEMENT OF UNSTABLE CORONARY DISEASE 199
Clinical suspicion of ACS
Physical examination
ECG monitoring, Blood samples
Persistent ST
segment elevation
No persistent
ST segment elevation
Undetermined
diagnosis
Thrombolysis
PCI
ASA. LMW heparin
Clopidogrel*, beta-blockers, Nitrates
ASA
High risk
Low risk
Second troponin measurement
Gp2b/3a
Coronary angiography
Positive
Twice negative
PCI CABG or medical management
depending upon clinical and
angiographic features
*Omit clopidogrel if the patient is likely to go to CABG within 5 days
Stress test
Coronary angiography
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).
Infarct limitation
In centres where immediate access is available to the cardiac
catheterization laboratory, the treatment of choice for limitation
of infarct size and severity is generally considered to be
primary angioplasty. However, at the present time, many hospitals
do not have such immediate access available, and in such
cases, since prevention of death and other serious complications
is directly related to the speed with which opening of
the infarct-related artery can be achieved, antithrombotic/
fibrinolytic treatment should be instituted. Aspirin and thrombolytic
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
and tenecteplase. 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.
Heparin or, more commonly low-molecular-weight heparin
administered subcutaneously, is needed to maintain patency of
a vessel opened by aspirin plus thrombolysis when alteplase,
reteplase or tenecteplase are used; this is not the case, however,
for streptokinase. Recent evidence suggests that the
additional use of clopidogrel in the early course of myocardial
infarction improves outcome further, over and above the benefit
seen with aspirin and 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 atenolol group
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 benefit
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, trandolapril and
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