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Acute coronary syndrome Part
2
Ensure that appropriate treatment
is initiated at the right time
BY Matthew Bennett, MD and Andrew
Ignaszewski, MD
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How and when does treatment begin?
The incidence of acute coronary syndrome
(ACS) is rising as the prevalence of vascular disease increases.
With treatment advances, however, mortality from this cluster of
diseases is declining. In the mid-1970s, the 21-day mortality from
ACS was 27.1%.1
In a trial published within the last year, the 28-day mortality
was 7.2%.2
Diagnosis of ACS is made by integrating information culled from
the history, physical exam and ancillary tests, including cardiac
biomarkers, chest x-ray and electrocardiogram (see
part one of this article Parkhurst Exchange, May 2006).
Although most patients with chest pain end
up in the emergency department (ED), some will present to their
family physician. If an individual has no contraindications and
the suspicion of ACS is high, it's appropriate to ask the patient
to chew and swallow ASA (162-325 mg). Similarly in the ED —
and in the absence of contraindications — a patient with a
high probability of being diagnosed with ACS should also be given
ASA.3,4
Support for ASA to treat ACS stems primarily
from the second International Study of Infarct Survival (ISIS-2)
trial. Researchers randomized 17,187 patients with ACS to four treatment
arms in a 2 x 2 factorial design (placebo vs ASA dose vs streptokinase
vs combined ASA and streptokinase). Overall, the relative risk reduction
(RRR) in vascular death at five weeks with ASA alone was 23% compared
to placebo. Interestingly, this was similar to the RRR achieved
by streptokinase alone (25%) when compared to placebo. The combination
therapy (streptokinase and ASA) was superior to each of the individual
treatments, demonstrating a RRR of 42% vs placebo.5
Other therapeutic modalities are introduced
to patients suspected of having ACS. They include treatments based
on reperfusion and target the coagulation cascade (thrombolysis,
clopidogrel, glycoprotein 2B3A inhibitors, heparin and angioplasty).
Other therapies work by a variety of mechanisms, including reducing
ischemia and improving remodelling (beta-blockers, nitroglycerin,
inhaled oxygen, modifiers of the renin angiotensin system and HMG-CoA
reductase inhibitors). These therapeutic measures should only be
used when the likelihood of ACS is high, particularly with anticoagulation
and thrombolysis, which may increase mortality if the diagnosis
is incorrect.
What about
troponin levels?
The question is: should one wait for the troponin level before initiating
treatment? The troponin level may sometimes be detected as late
as eight hours after onset of chest pain. Because "time is muscle,"
it's important to initiate treatment before this occurs. As such,
it's important to make a diagnosis and not wait for the results
of the serum troponin concentration to decide to treat.
When should
revascularization be considered?
Treatment algorithms for ACS are divided into two groups —
ST segment elevation myocardial infarction (STEMI), and the two
entities of unstable angina (UA) and non-ST segment elevation myocardial
infarction (NSTEMI). Treatment between these two groups is very
different.
The pathophysiology of STEMI is that a plaque
ruptures upon which a thrombus forms, resulting in complete occlusion
of the coronary artery. This manifests as ST elevation on the ECG,
and early revascularization is recommended in these patients. The
primary methods of emergency revascularization are thrombolysis
and emergency angioplasty with stent placement (primary percutaneous
coronary intervention [PCI]). The goal for patients with STEMI is
to administer thrombolysis within 30 minutes (door to needle time
[DN]) or PCI by 90 minutes (door to balloon time [DB]).3
How well
does fibrinolysis work?
The Fibrinolytic Therapy Trialists' Collaborative Group performed
a meta-analysis of studies comparing fibrinolysis to controls in
more than 1,000 individuals. In the nine trials that randomized
almost 60,000 patients with MI, a 21% RRR in mortality was noted
in the STEMI subgroup with fibrinolysis vs placebo.6
Fibrinolytics are divided into two classes:
the fibrin-specific fibrinolytics (i.e. alteplase, reteplase and
tenecteplase), and the non-specific fibrinolytics (i.e. streptokinase).
Overall, the achievement of Thrombolysis in Myocardial Infarction
(TIMI-3) grading flow (return of normal coronary artery flow) —
a surrogate for survival of person — is 32%, 54%, 60% and 63%
for streptokinase, alteplase, reteplase and tenecteplase, respectively.6
When is it
too late for thrombolysis after onset of chest pain?
With any treatment, one must weigh the risks vs the benefits. With
thrombolysis, the risks are approximately 0.9-1.6% and 1.1-1.8%
for stroke and major bleeding with fibrin-specific fibrinolytics.6-8
Because the benefit of fibrinolytics decreases with duration, and
onset of chest pain increases, administration of fibrinolysis is
only recommended up to 12 hours after onset of chest pain. Afterwards,
the risk outweighs the benefit.3
Keep in mind that "lysing" a thrombus creates
more thrombogenic surface area and, as such, co-administration of
heparin — unfractionated heparin (UFH) or low molecular weight
heparin (LMWH) — is suggested when using fibrin-specific fibrinolytics.
Platelet glycoprotein 2B3A inhibitors (G2B3A-I) are only recommended
in select patients (i.e. abciximab with half-dose reteplase or tenecteplase
to prevent reinfarction of individuals with an anterior MI younger
than 75 years and have no risk factors for bleeding).3
Matthew Bennett, MD, FRCPC is a cardiology fellow in
the Division of Cardiology at the University of British Columbia.
Andrew Ignaszewski, MD, FRCPC is Medical Director of
the Healthy Heart Program at St. Paul's Hospital in Vancouver and
a clinical associate professor in the Division of Cardiology at
the University of British Columbia.
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