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C H A P T E R 146

ACUTE CORONARY SYNDROMES

John W. Eikelboom and Jeffrey I. Weitz

Acute coronary syndromes (ACS) lead to millions of hospital admis- facilitate lysis of intracoronary thrombus. Antithrombotic drugs are
sions worldwide each year and are a leading cause of death. Anti- also used to prevent thrombus formation on the guide wires, catheters,
thrombotic therapies are a cornerstone in the immediate and and stents used to open occluded arteries, and to prevent and treat
long-term management of ACS, reducing the risk of myocardial left ventricular thrombus formation.
infarction (MI) and death in both medically and invasively managed Although the pathophysiology is similar irrespective of whether
patients. This chapter reviews fibrinolytic, antiplatelet, and antico- patients present with STEMI or NSTE ACS, only STEMI patients
agulant therapies in the treatment of patients with ACS and provides benefit from immediate reperfusion therapy. This difference reflects
a practical guide to several common hemostatic and thrombotic the fact that most patients with NSTEMI do not have an occluded
problems encountered in this patient population. infarct-related coronary artery. Instead, they develop MI as a conse-
quence of distal embolization of thrombus.

CLASSIFICATION
REPERFUSION THERAPY FOR ST-SEGMENT ELEVATION
The clinical classification of ACS is based on the electrocardiogram MYOCARDIAL INFARCTION
(ECG) at the time of presentation and on blood levels of cardiac
biomarkers (troponin, creatine kinase). Patients with ST-segment Effective approaches to coronary reperfusion include mechanical
elevation on the ECG and elevated cardiac biomarkers are diagnosed (primary percutaneous coronary intervention [PCI]) and pharmaco-
with ST-segment elevation MI (STEMI). Patients with non–ST-seg- logic (fibrinolytic therapy) methods.
ment elevation (NSTE) ACS are subdivided according to whether or
not they have elevated blood levels of cardiac biomarkers; those with
elevated cardiac biomarkers are diagnosed with non–ST-segment Primary Percutaneous Coronary Intervention
elevation MI (NSTEMI), and those without elevated cardiac bio-
markers are diagnosed with unstable angina. 1–3 Primary PCI is preferred over fibrinolytic therapy in patients with
STEMI because it produces higher patency rates and does not cause
intracranial bleeding. Unlike fibrinolysis, which only treats the
PATHOPHYSIOLOGY thrombus, primary PCI also allows treatment of the underlying
atherosclerotic plaque. However, many centers lack the facilities and
4
Atherothrombosis plays a central role in the pathogenesis of ACS. expertise to perform urgent coronary interventions, and only a
Hypertension, abnormal blood glucose levels, dyslipidemia, and toxins minority of STEMI patients worldwide is treated with primary
5,6
contained in tobacco cause endothelial injury. Lipid accumulation PCI. Patients undergoing primary PCI are routinely treated with
promotes an inflammatory response characterized by the recruitment anticoagulant and antiplatelet therapy (discussed in sections on
of macrophages, smooth muscle cells, and fibroblasts to the site of injury antiplatelet therapy and anticoagulant therapy).
and the formation of increasingly complex and unstable plaques with
a necrotic core and fibrous cap. Disruption of the fibrous cap by shear
forces and its degradation by enzymatic and cellular processes expose the Fibrinolytic Therapy
plaque contents to the blood. Platelets adhere to exposed subendothelial
proteins and become activated and aggregate. Exposed tissue factor Fibrinolytic drugs are plasminogen activators that initiate fibrinolysis
induces thrombin generation on cellular surfaces, further promoting by converting plasminogen to plasmin. Plasmin degrades fibrin
the formation of a platelet-fibrin thrombus that can occlude coronary resulting in clot lysis and recanalization of thrombotic occlusion.
blood flow. These processes are described in more detail in Chapter 144. Restoration of coronary blood flow limits infarct size and improves
The clinical manifestations of coronary atherothrombosis are myocardial function and survival.
influenced by the extent and duration of obstruction to blood flow The pharmacologic characteristics of the fibrinolytic drugs most
and the presence or absence of a collateral circulation. Patients with commonly used in the management of ACS are summarized in
small plaques that do not significantly impair blood flow generally Table 146.1. Streptokinase was the first agent to be evaluated in
remain asymptomatic. Patients with significant flow-limiting plaques large-scale randomized controlled trials. A non–fibrin-specific agent,
may develop ischemic symptoms (e.g., chest pain, breathlessness) streptokinase, indirectly activates plasminogen, whereas the more
during exertion when myocardial oxygen demand exceeds supply. fibrin-specific agents alteplase, reteplase, and tenecteplase directly
Patients with acute plaque disruption with superimposed thrombus convert plasminogen to plasmin. Reteplase and tenecteplase have
formation that completely obstructs coronary blood flow typically longer half-lives than alteplase, enabling them to be given by double-
present with STEMI unless there is an adequate collateral circulation. or single-bolus injection, respectively, which simplifies administra-
If obstruction to blood flow is transient or partial, patients typically tion. The direct-acting fibrinolytic agents are more fibrin specific
present with NSTE ACS. If myocardial ischemia results in ventricular than streptokinase because they bind to fibrin, where they convert
fibrillation, sudden cardiac death supervenes. fibrin-bound plasminogen to plasmin. Consequently, these agents
produce a less marked systemic lytic state than streptokinase, which
has no fibrin affinity. Avoidance of a systemic lytic state, which is
ANTITHROMBOTIC MANAGEMENT characterized by a reduction in the circulating level of fibrinogen,
is an important potential advantage of fibrin-specific drugs because
The goal of antithrombotic therapies in patients with ACS is to this can be expected to be associated with a lower risk of bleeding
prevent new thrombus formation at the site of plaque disruption and complications.

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