ANTI-ISCHAEMIC AGENTS

1. -blockers assist symptom control. -blockers, administrered orally, should be

started in the absence of contraindication. Caution is suggested in the early use of
IV -blockers, which should be targeted to specific indications and should be
avoided with haemodynamic instability and heart failure. IV therapy may be
warranted for high-risk patiens (e.g. with ongoing pain and hypertension) without
contraindication to therapy. In these patients, meteprolol at 5 mg IV is commonly
given incrementally every 5 min until symptoms are relieved, side-effects are
experienced or a dose of 15 mg is reached. Ideally medication is titrated to attain
a heart rate of 55-60 beats/min.
2. Nitrates. Sublingual nitroglycerine 300-600 g is usually given in two doses at
least some minutes apart (monitoring blood pressure) to realive ischaemic pain.
Patiens with ongoing pain may receive IV nitrates. Evidence of improved
outcome is lacking. Hypotension is a contraindication.
3. Calcium channel blockers may provide symptom relief when there are problems
with -blockers and nitrates. They may have a neutral or negative effect on
mortality and progression to MI. Nifedipine without con-comitant beta-blocker
may increase mortality. As sole agent, only those egents that reduce heart rate
should be used(e.g. diltiazem or verapamil)
ANTIPLATELET THERAPIES
1. Aspirin (acetylsalicylic acid) decreases death or nonfatal MI in patients with
NSTEACS by approximately 50%.
2. Clopidogrel (in combination with aspirin) was demonstratedin Clopidogrel in
Unstable angina to prevent Recurrent Event (CURE) study to produce 20%
reductions in adverse events (compared to aspirin alone) when commenced early
and continued in patients with NSDTEMI. Reduction was mainly in MI.
Significant early in-hospital benefit was seen. Clopidogrel is prefferd to
ticlopidine, its older thicnopyridine.(Clopidogrel is generally used in conjuction
with aspirine In NSTEACS regardless of whether a conservative or invasive
approach is planned. Its introduction or continuation should be reviewed if CABG
is immediately imminent).
3. GP IIb/IIIa receptor blocker reduce the 30-day risk of non-fatal MI by 38% in
NSTEMI patiens under-going PCI. Benefit seems to be confined to high-risk

patiens (elevated tropinins) undergoing PCI.Pre-treatment with tirofiban may be

useful in thise group. They have not been shown to be beneficial in the routine
management of medically treated patients (GUSTO-IV-ACS)
ANTITHROMBINS AND ANTICOAGULANTS
Heparins significantly reduce the composite of MI or death in NSTEACS patients
receiving aspirin, although the endpoint of mortality alone has not been significant.
The same is true of LMWHs.
Meta-analysis that compares regimens of LMWHs to regimens of UFH found
a minimal or less significant reduction in the composite of death, MI and need for
urgent revascularisation in favour of LMWHs than found when compared in STEMI
patients. However dispite higher acquisition cost, their simplicity, lack of need for
monitoring and acceptable safety profile perhaps favour their administration.
Fondaparinux compared to enoxaparin in NSTEACS had similar early
efficacy but appeared to do so with fewer bleeding complications. At later follow-up,
fondaparinux was associated with lower mortality and cerebrovascular accidents;
most of the benefit seemed to accrue from its lesser bleeding rate. Substitution of
fondaparinux for enoxaparin might save 6 lives per 1.000 patients treated and might
result in 19 less bleeds. There is concern that fondaparinux is not sufficient to prevent
stent occlusion and concomitant UFH use is recommended in patients undergoing
PCI.
ONGOING AND DISCHARGE CARE OF ACS (SECONDARY PREVENTION)
(FIGURE 16, 17)
A member of therapics have been studied in the long term (secondary) treatment of
ACS, both STEMI and NSTEACS.
1. Aspirin (75-160 mg/day) should be continued unless there are strong
contraindication. In the first 2 years after MI, aspirin therapy results in an absolute
decrease of approximately 36 vascular events (vascular death or non-fatal MI or
stroke) for every 1.000 patients treated
2. Clopidogrel is generally continued throughout the hospital stay in both STEMI
and NSTEMI. In patients who have undergonePCI, continued treatment after
discharge is beneficial, although the duration of that treatmentis unknown and
dependent upon the nature of the stent placed. Given in conjuction with aspirin,
clopidogrelis proven to be of benefit when administered long-term to patients at

high risk of future cardiovascular events (the CURE study), althoughit is

associated with an increased risk of bleeding. Clopidogrel is also a useful
treatment in patient with aspirin resistance.
3. -blockers significantly reduce the incidenceof sudden and non-sudden cardiac
death in survivors of MI. Benefit is prolongedand is most marked in hig-risk
patients, for example those with extensive infarction. Given at the time Of MI and
continued orally, -blockers
Have an early and significant effect on mortality, whichis apparent at 7 days,
although therapy is not appropriate in patients with contraindications. Long term
administration after MI is also associated with survival and reinfarction benefit
Late interventions

Patients; n RCTs; n

Anticoagulant
Cardiac Rehabilitation
Beta-Blockers
Cholesterol Reduction
Antplatelet agents
ACE Inhibitors
Calcium Antagonists
Class 1 Antiarrhythm
Amiodarone

4975
5022
24298
10775
18411
5984
13114
6300
1557

Late interventions in myocardial infarction

12
23
26
8
10
3
6
18
9

0.5

4. ACE inhibitors arerecommended in the treatment of all patients recovering from

MI. They significantlyreduce mortality in high-risk patients or with symptomatic
failure when commenced deuring recovery from MI.. Ptients with anterior MI and
ejection fraction < 40% maintained on long-term ACE inhibitortherapy may

experience a 20% relative reduction in mortality and a significant reduction in the

incidence of LV failure. Benefit is still seen at 4 years post treatment. Very early
introduction of ACE inhibitors within36 h of infarction) may also reduce
mortality. In patients intolerant of ACE inhibitors an ACE receptor blocker may
be used.
The aldosterone antagonist eplerenone reduce mortality in asymptomatic
patients with low EF post-MI and already receiving -blockers and ACE
inhibitors (see chapter 20).
5. Lipid-lowering agents. Statins should b commenced in hospital for all patiens
with ACS. Benefit is maximal in patients with elevated cholesterol and other
factors,but benefit is present at all cholesterol levels. Loweringeleveted
cholesterol concentrations following MI results in a decrease in mortalityand
reinfarction. Although data are conflicting, benefit may be evident within 30 days
and therapy should be commenced as early as possible. It is thought that statins
reduce inporcholesterolaemia and inflammation stabilizing the lipid core, and
early introduction may be beneficial.
6. Other anti-ischemin agents.
Routine us of calcium channel blockers does not improve outcome and certain
agents have been suggested to cause harm. They may be of symptomatic use in
patients intolerant of
-blockers or where a concomitant antihypertensive
effect is needed.
Carvedilol may be of benefitin patients with ACS
7. Antiarrhythmic therapy is not routinely continued. In the Cardiac Arrhytmia
Suppression Trial (CAST) prolonged flecainide therapywas used to
suppressvetricular ectopy. Despite doing so. Mortality increased. Amiodarone in
low doses (200 mg/day) may reduce mortality, but results of definitive trials area
waited and it has significant side-effect. It cannot currently be recommended as
routine therapy. For patients with actual or who are at high risk of ventricular
arrhythmia, concideration may be given to long term amiodarone or use an
implantable defibrilator
8. Warfarin given alone or in combination with aspirin is associated with lower rates
of composite of death reinfarction and thromboembolic stroke. Concerns about
bleeding (especially in elderly) probably still see its clinical application restricted.
Wrfarin is useful for patients with proven myocardial thrombus, a large area of
regional wall motion abnormality or generalized thrombotic tendency

9. Lifestyle advice ismost important and all patients should cease smoking and
receive advice on exercise an diet. Diabetes should be tightly controlled.
MYOCARDIAL INFRACTION IN THE INTENSIVE CARE UNIT
Myocardial ischemia is acommon problem in thr ICU. It also commonly complicates
perioperative care of major surgery, with mortality of up to 15-25%. Diagnostic
criteria are uncertain but a system has been proposed by Devereaux et al.There are
few randomized controlled trials to guide therapy of postoperative infarction, or
infarction complicating the care of critically ill. Many patients with such
presentations were excluded from trials of ACS therapy.
The pathophysiology of postoperative infarction and infarction in ICU
patients is probably different to that of ACS. Studies suggest that, in the presence of
severe ischaemia, left main disease and triple-vessel disease are common and that
ischemia is secondary to oxygen supply and demand problems rather than
thrombosis. However, data on this are conflicting. The absence of thrombosis as an
underlying pathological mechanism in many suggest that standard aggressive
antithrombus therapies will have different risk-benefit profiles, and that harm is
exacerbated by the often high bleeding risk of these patients.
The patiens with significant ST-segment elevation and haemodynamic
instability in the ICU present a difficult problem. Where underlying coronary artery is
considered likely, an invasive approach is usually necessary.Thrombolysis is usually
precluded by bleeding risk and by uncertainty regarding the causative process.
Angiography will allow diagnosis and intervention if necessary; however, the use of
adjunctive therapy (short-and intermediate term) may be associated with significant
bleeding. Reversible factors such as hypoxia, severe anaemia, anxiety andtachycardia
must all be controlled where possible. Hypotension may limit the ability to administer
-blockers and control tachycardia.
Echocardiography may be useful in confirming regional wall motion
abnormality and in confirming the amount of myocardium at risk. Of Interest is the
Takotsubo syndrome, where anterior ST-segment elevation and tipical ballooning an
echocardiography, often in association with elevated troponins, may occur in the
presence of normal coronary arteries.
BLEEDING COMPLICATIONS POSTREPERFUSION THERAPY
The increased use of aggressive fibrinolytic regimens and adjunctive reperfusion
agents has led to troublesome bleeding in some patients. Some knowledge of reversal
of these agents is necessary.

1. GPIIb/IIIa blockers,Abciximab, a chimeric monoclonal antibody, has a short halflife, but antipletelet activity is still prolonged at 24-28 h. Fortunately transfused
platelet are not affected and will assist with bleeding reversal. The newer agent
tirofiban and eptifibitide have very short half-life and antiplatelet action returns to
normal 4-8 h after discontinuation. During this periode, however, antipletelet
action is profound. It is suggested that administration of fresh frozen plasma (8
units) and platelets (2 units)is likely necessary to reverse antiplatet action.
2. Clopidogrel. It is recommendedthat clopidogrel be ceased at least 5 days before
elective CABG, but this is not always possible in emergent surgery or in unstable
cases. Major bleeding rates may approach10% in these cases. Phrmacology
suggest that platelet transfusionare necessary to moderate this but dose is
unknown.
3. LMWHs. Reversal of LMWHs with protamine is variable and incomplete, even
with doses of 100 mg. Protamine may reverse up to 60% of LMWH action. It
suggested that doses of protamine should equal doses of enoxaparin administrated
on a milligram-per-milligram scale
4. Fibrinolytic agents. In the setting of life-threatening bleeding, large doses of
cryoprecipitate (10-20 units) may be required to replace fibrinogen (target > 1g/l)
and coagulation factors (especially factor VIII). Fresh frozen plasma may
supplement factor V and VIII levels. Platelet transfusionsat high dose may replace
platelets and supplement factor V levels. -Aminocaproic acid at a dose of 5 g
(0.1 g/kg) over 30-60min followed by continuous infusion (0.5-1.0 g/h) may
assist with bleeding control.
OUTCOME OF MYOCARDIAL INFARCTION
The in-hospital mortality from acute MI has been steadily decreasing over the past
three decades from 15% to 30% in the 1970s to approximately 10% in 1980 and now
to around 8-9 % in the new millennium. Despite improved mortality, 60 % of all
deaths occur within the first hour (usually from VF), and usually before reaching a
medical facility. Modern management of acute MI has undoubtedly contributed to
decreased mortality. Further significant reduction in mortality must come from
management strategis within the first hours of the onset of symptoms.

The major in-hospital shanges are likely to come from :

Better hospital organization to increase acces to PCI
Increase use of adjuvant therapics and discharge medications

Increase rates of thrombolysis or PCI in eligible patient

The letter cannot be underestimated. In one study, the in-hospital mortality was 5.7%
for those who were eligible for but did not receive such therapy (9.3% versus 18% in
eligible women who did not receive therapy, 10.5% versus 1% in eligible elderly). Up
to 24% of eligible patients di not receive reperfussion therapy.
NEW INFORMATION
The conclusion can be summarized.
Cardiac troponin level is frequently increased in hospitalized patients in the
absence of an ACS
It portends poor short and long term outcomes
Most of these patients have an alternative explanation for cardiac troponin
increase
Cardiac diagnostic procedures are frequently unhelpful in excluding a non-ACSrelated troponin increase
Essentially Troponin 1 level had poor accuracy in discriminating patients with and
without ACS. Alternative diagnoses included; xepsis, acute left heart failure,
cerebrovascular events and wide range of other conditions