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C HAP TE R 22 / Acute Coronary Syndromes 521

1. The occurrence of a change in neurological status during or af- reteplase. No improvement in mortality was demonstrated with
ter reperfusion therapy, particularly within the first 24 hours af- combination therapy but there was a modest reduction in clinical
ter initiation of treatment, is considered to be due to ICH until events, such as reinfarction, ventricular fibrillation, and ventricu-
proven otherwise. Fibrinolytic, antiplatelet, and anticoagulant lar septal defect. 58,59 However, there was an increase in bleeding
therapies should be discontinued until brain imaging scan complications and transfusion rates with combination therapy.
shows no evidence of ICH. (Class I, level of evidence: A) Patients older than 75 years had a higher incidence of ICH. 59
2. Neurology and/or neurosurgery or hematology consultations The ASSENT III trial compared full-dose tenecteplase (TNK-
should be obtained for patients with STEMI who have ICH, as t-PA) plus standard dose UFH, full-dose tenecteplase (TNK-t-PA)
dictated by clinical circumstances. (Class I, level of evidence: C) plus enoxaparin, and half-dose tenecteplase (TNK-t-PA) plus ab-
3. In patients with ICH, infusions of cryoprecipitate, fresh frozen ciximab. The combination therapy had no survival advantage after
60
plasma, protamine, and platelets should be given, as dictated by 30 days and had increased bleeding complications. Combination
clinical circumstances. (Class I, level of evidence: C)2 therapy has no mortality advantage in STEMI but is associated
with slight reductions in cardiovascular clinical events. 58
Contraindications of Fibrinolytic Therapy. There are
The ACC/AHA guidelines for STEMI state that combination
both absolute and relative contraindications to fibrinolytic ther-
pharmacological reperfusion with half-dose reteplase or tenecteplase
apy. Contraindications are listed in Table 22-5.
may be considered for the prevention of reinfarction and other com-
plications of STEMI in selected patients meeting the following crite-
Combination Therapy: Fibrinolytic Agents
and Glycoprotein (GP) IIb/IIIa Inhibitors ria: anterior MI, younger than 75 years, and no risk factors for bleed-
2
ing in whom an early referral for angiography and PCI is planned.
Pharmacological reperfusion with fibrinolytic agents does not pro-
duce complete restoration of coronary blood flow and TIMI flow 3
in all patients. 53 (See Display 22-1.) Further clinical studies to im- REPERFUSION STRATEGIES FOR
prove reperfusion with STEMI involved the use of GP IIb/IIIa in-
hibitors. Intracoronary thrombus formation occurs when fibrinogen STEMI AND UA/NSTEMI
and other adhesive proteins bind to adjacent platelets by means of
Prompt and complete restoration of blood flow in the infarct ar-
the GP IIb/IIIa receptor sites. Blocking the GP IIb/IIIa receptors can
tery is necessary to prevent myocardial necrosis and improve
decrease thrombus formation. There are three GP IIb/IIIa receptor
short- and long-term outcomes. Immediate reperfusion therapy
inhibitors currently available for clinical use: abciximab, tirofiban,
can be achieved by pharmacological therapy (fibrinolysis), PCI
and eptifibatide. Abciximab, a monoclonal antibody, is directed
(balloon angioplasty with or without deployment of an intracoro-
against the receptor, while tirofiban and eptifibatide are high affinity
nonantibody receptor inhibitors. 54 nary stent) with pharmacological measures to prevent thrombosis.
Surgical reperfusion in a timely manner is not usually possible in
The use of GP IIb/IIIa inhibitors alone was examined in patients
STEMI; candidates for reperfusion routinely receive either fibri-
with STEMI and the ability to restore TIMI flow 3. These agents in
nolysis or a catheter-based treatment. 2
isolation do not adequately restore reperfusion to make GP IIb/IIIa
inhibitors alone a viable pharmacological strategy for STEMI. 55–57 ACC/AHA Guidelines for Management of Patients with
2
STEMI recommend that all STEMI patients should undergo rapid
Combination therapy has been proposed as a method to increase
evaluation for reperfusion therapy and have a reperfusion strategy
reperfusion rates. Two randomized studies (Global Utilization of
implemented promptly after contact with the medical system (Class
Strategies to open Occluded Coronary Arteries-V [GUSTO V]
I, level of evidence: A). In STEMI, rapid primary PCI results in su-
and Assessment of the Safety and Efficacy of a New Throm-
perior clinical outcomes compared to fibrinolysis. 61–66 However, the
bolytic-III [ASSENT III]) evaluated the effect on mortality and
cardiovascular clinical events in STEMI. 58 The GUSTO V trial preferred reperfusion therapy for STEMI must take into account
the location of the patient, the response time and the expertise of the
compared half-dose reteplase and abciximab with full-dose
paramedical/ambulance personnel, their relationship to the regional
health care facility, and the availability, capability, and expertise of
12
DISPLAY 22-1 Timi Flow Grade 98 the medical personnel at the facility (Table 22-3).
The TIMI (Thrombolysis in Myocardial Infarction) trial Primary PCI for STEMI
flow grade classification characterizes coronary blood
flow in the infarct-related artery, which is usually meas- Guidelines from the ACC/AHA/European Society of Cardiology
ured at 60 to 90 minutes after the administration of fibri- recommend a treatment goal of 90 minutes or less for door-to-
nolytic therapy balloon time (or time from initial medical contact to treatment).
TIMI 0 refers to the absence of any antegrade flow beyond This measure is incorporated into national, publicly reported
a coronary occlusion. quality measures for hospital performance. The Health Quality Al-
TIMI 1 flow is faint antegrade coronary flow beyond the liance program, which is a combined effort of the Centers for
occlusion, although filling of the distal coronary bed is Medicare and Medicaid Services and the Joint Commission, in-
incomplete.
TIMI 2 flow is delayed or sluggish antegrade flow with cludes door-to-balloon time among its core measures of quality of
complete filling of the distal territory. care for acute MI. When both reperfusion strategies can be rapidly
TIMI 3 flow is normal flow, which fills the distal coronary performed current evidence supports the use of primary PCI
bed completely. based on its superiority in establishing coronary blood flow and
lower risk of reinfarction and intracerebral hemorrhage. 11
From Chesebro, J. H., Knatterud, G., Roberts, R., et al. (1987). Thrombolysis in PCI is the best option for patients with cardiogenic shock and
Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous
tissue plasminogen activator and intravenous streptokinase. Clinical findings through the only option for patients with contraindications to fibrinolytic
hospital discharge. Circulation, 76(1), 142–154.6 6 therapy. However, fibrinolytic therapy remains a practical option