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CHAPTER 37: Myocardial Ischemia 299

for thrombolytic therapy are listed in Table 37-2. Because of the small, TNK-t-PA is given as a single bolus, adjusted for weight. A single bolus
but nonetheless significant, risk of a bleeding complication, most notably of TNK-t-PA has been shown to produce coronary flow rates identical
intracranial hemorrhage, selection of patients with acute MI for admin- to those seen with accelerated t-PA, with equivalent 30-day mortality
istration of a thrombolytic agent should be undertaken with prudence and bleeding rates. 49
and caution. That is of special importance in ICU patients, who may Because these newer agents in general have equivalent efficacy and side
have a predisposition to bleeding complications because of multiple effect profiles, at no current additional cost compared to t-PA, and because
factors. In the surgical patient, fibrinolysis may pose a prohibitive risk they are simpler to administer, they have gained popularity. An ideal fibri-
and emergent coronary angiography (with percutaneous coronary nolytic agent would have greater fibrin specificity, slower clearance from
intervention [PCI] as clinically indicated) may be preferable. the circulation, and more resistance to plasma protease inhibitors, but has
In contrast to the treatment of STEMI, fibrinolytics have shown no not yet been developed.
benefit and an increased risk of adverse events when used for the treat-
ment of unstable angina/NSTEMI. Based on these findings, there is ■ PRIMARY PCI IN ACUTE MYOCARDIAL INFARCTION
45
currently no role for thrombolytic agents in these latter syndromes. The major advantages of primary PCI over thrombolytic therapy include
44
Thrombolytic Agents: Streptokinase was the original lytic agent used in a higher rate of normal (TIMI grade 3) flow, lower risk of intracranial
MI, but has now been superseded by tissue plasminogen activator (t-PA), hemorrhage and the ability to stratify risk based on the severity and
a recombinant protein that is more fibrin-selective than streptokinase and distribution of coronary artery disease. Patients ineligible for fibrinolytic
produces a higher early coronary patency rate (70%-80%). The Global therapy obviously should be considered for primary PCI. In addition, data
Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded from several randomized trials have suggested that PCI is preferable to
Coronary Arteries (GUSTO) trial compared SK to t-PA in 41,101 patients thrombolytic therapy for AMI patients at higher risk, including those over
with STEMI, and demonstrated a small but significant survival benefit for 75 years old, those with anterior infarctions, and those with hemodynamic
t-PA (1.1% absolute, 15% relative reduction). The GUSTO angiographic instability. 50,51 The largest of these trials is the GUSTO-IIb Angioplasty
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substudy showed that the difference in clinical efficacy resulted from the Substudy, which randomized 1138 patients. At 30 days, there was a clinical
difference in patency rates. t-PA is usually given in an accelerated regimen benefit in the combined primary end points of death, nonfatal reinfarc-
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consisting of a 15-mg bolus, 0.75 mg/kg (up to 50 mg) IV over the initial tion, and nonfatal disabling stroke in the patients treated with PTCA
30 minutes, and 0.5 mg/kg (up to 35 mg) over the next 60 minutes. compared to t-PA, but no difference in the “hard” end points of death and
Reteplase (r-PA), is a deletion mutant of t-PA with an extended half- myocardial infarction at 30 days. 51
life, and is given as two 10-mg boluses 30 minutes apart. Reteplase was Meta-analyses comparing direct PCI with thrombolytic therapy found
originally evaluated in angiographic trials which demonstrated improved lower rates of mortality and reinfarction among those receiving direct
coronary flow at 90 minutes compared to t-PA, but subsequent trials PCI. 52,53 Thus, direct angioplasty, if performed in a timely manner
showed similar 30-day mortality and bleeding rates. 48 ( ideally within 60 minutes) by highly experienced personnel, may be
Tenecteplase (TNK-t-PA) is a genetically engineered t-PA mutant with the preferred method of revascularization since it offers more complete
amino acid substitutions that result in prolonged half-life, resistance to revascularization with improved restoration of normal coronary blood
plasminogen-activator inhibitor-1, and increased fibrin specificity. flow and detailed information about coronary anatomy. There are certain
subpopulations in which primary PCI is clearly preferred, and other
populations in which the data are suggestive of benefit. These subsets are
listed in Table 37-3. More important than the method of revasculariza-
TABLE 37-2 Indications for and Contraindications to Thrombolytic Therapy in tion is the time to revascularization, and that this should be achieved in
Acute Myocardial Infarction
the most efficient and expeditious manner possible. It is important to
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Indications keep in mind that early, complete, and sustained reperfusion after myo-
• Symptoms consistent with acute myocardial infarction cardial infarction is known to decrease 30-day mortality. The preferred
• ECG showing 1-mm (0.1 mV) ST elevation in at least two contiguous leads, or new left method for reperfusion in STEMI is PCI only if it can be done within
bundle-branch block a timely manner. Practical considerations regarding transport to a PCI
• Presentation within 12 hours of symptom onset capable facility should be carefully reviewed before foregoing fibrinolyt-
• Absence of contraindications ics for PCI. Early recognition and diagnosis of STEMI are key to achiev-
ing the desired door-to-needle (or medical contact–to-needle) time for
Contraindications
initiation of fibrinolytic therapy of 30 minutes or door-to-balloon (or
Absolute medical contact–to-balloon) time for PCI under 90 minutes. Achieving
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• Active internal bleeding reperfusion in timely matter correlates with improvement in ultimate
• Intracranial neoplasm, aneurysm, or A-V malformation
• Stroke or neurosurgery within 6 weeks
• Trauma or major surgery within 2 weeks which could be a potential source of serious TABLE 37-3 Situations in Which Primary Angioplasty Is Preferred in Acute
rebleeding Myocardial Infarction
• Aortic dissection
Situations in Which PTCA Is Clearly Preferable to Thrombolytics
Relative • Contraindications to thrombolytic therapy
• Prolonged (>10 minutes) or clearly traumatic cardiopulmonary resuscitation a • Cardiogenic shock
• Noncompressible vascular punctures • Patients in whom uncertain diagnosis prompted cardiac catheterization which revealed
• Severe uncontrolled hypertension (>200/110 mm Hg) a coronary occlusion
• Trauma or major surgery within 6 weeks (but more than 2 weeks) Situations in Which PTCA May Be Preferable to Thrombolytics
• Preexisting coagulopathy or current use of anticoagulants with INR >2-3
• Active peptic ulcer • Elderly patients (>75 years)
• Infective endocarditis • Hemodynamic instability
• Pregnancy • Patients with prior coronary artery bypass grafting
• Chronic severe hypertension • Large anterior infarction
• Patients with prior myocardial infarction
a Could be an absolute contraindication in low-risk patients with myocardial infarction.

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