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C HAP TE R 22 / Acute Coronary Syndromes 519

Table 22-4 ■ COMPARISON OF FIBRINOLYTIC AGENTS
Streptokinase Alteplase Reteplase Tenecteplase-tPA
Dose 1.5 million units over 30 Up to 100 mg in 90 10 U 2 each 30 to 50 mg based
to 60 minutes minutes (based over 2 minutes on weight †
on weight)*
Bolus administration No No Yes Yes
Antigenic Yes No No No
Allergic reactions (hypotension Yes No No No
most common)
Systemic fibrinogen depletion Marked Mild Moderate Minimal
90-minute patency rates, approximate % 50 75 7 75
TIMI grade 3 flow, % 32 54 60 63
Cost per dose (US$) in 2004 $613 $2,974 $2,750 $2,833 for 50 mg

*Bolus 15 mg, infusion 0.75 mg/kg times 30 minutes (maximum 50 mg), then 0.5 mg/kg not to exceed 35 mg over the next 60 minutes to an overall maximum of 100 mg.
† Thirty milligrams for weight less than 60 kg; 35 mg for 60 to 69 kg; 40 mg for 70 to 79 kg; 45 mg for 80 to 89 kg; 50 mg for 90 kg or more.
Antman, J.L., Anbe D.T., Armstrong P.W., et al. (2004). ACC/AHA Guidelines for the Management of Patients with ST-elevation Myocardial Infarction: A report of the American
College of Cardiology/American Heart Association task force on Practice Guidelines (writing Committee to Revise the 1999 Guidelines for the Management of Patients with Acute
Myocardial Infarction). JACC, e3–e170.
Indications for Fibrinolysis used fibrinolytic agents is presented below. Also see Tables 22-4
In the absence of contraindications, fibrinolytic therapy should be and 22-5.
administered to STEMI patients who have onset of symptoms Streptokinase. First-generation nonselective fibrinolytics in-
within the previous 12 hours and (1) ST-segment elevation greater clude streptokinase and urokinase, which activate plasminogen
than 0.1 mV in at least two contiguous precordial leads or at least systemically and are not fibrin specific. IV urokinase is not ap-
two adjacent limb leads or (2) new or presumably new LBBB (Class proved for STEMI. Tillet and Garner 39 discovered in 1933 that
2
I, level of evidence: A). The failure of IV fibrinolytic therapy to im- several strains of Streptococcus hemolyticus could dissolve human
prove clinical outcomes in the absence of STEMI or LBBB was
demonstrated in the Thrombolysis in Myocardial Ischemia 111B
28
(TIMI 111B), International Study of Infarct Survival 2 (ISIS-2), 29
and Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Table 22-5 ■ CONTRAINDICATIONS AND CAUTIONS FOR
30
Miocardico 1 (GISSI 1) trials. Fibrinolytic therapy has no signifi- FIBRINOLYSIS USE IN STEMI
cant benefit for management of patients with UA/NSTEMI with- Absolute Contraindications
out STEMI, true posterior MI, or a presumed new LBBB, and • Any prior intracranial hemorrhage
therefore is not recommended. 28–30 Table 22-4 compares character- • Known structural cerebral vascular lesion (e.g., AVM)
istics of the fibrinolytic agents. Contraindications and cautions of • Known malignant intracranial neoplasm (primary or metastatic)
• Ischemic stroke within 3 months EXCEPT acute ischemic stroke within
fibrinolytic agents are presented in Table 22-5. 3 hours
• Suspected aortic dissection
Prehospital Fibrinolytics • Active bleeding or bleeding diathesis (excluding menses)
Multiple trials 31–34 have demonstrated that prehospital fibrinolytic • Significant closed head or facial trauma within 3 months
administration can significantly decrease time from symptom on- Relative Contraindications
set to treatment. 12 Compared with historical control patients, pa- • History of chronic severe, poorly controlled hypertension
tients who received prehospital fibrinolysis achieved more rapid • Severe uncontrolled hypertension on presentation (SBP 180 mm Hg or
†
DBP 110 mm Hg)
32
31
resolution of ST-segment elevation. A meta-analysis of six ran- • History of prior ischemic stroke greater than 3 months, dementia, or
domized trials 33–38 demonstrated improved outcomes and lower known intracranial pathology not covered in contraindications
mortality with prehospital fibrinolysis. • Traumatic or prolonged (greater than 10 minutes) CPR or major surgery
Prehospital fibrinolysis protocols are reasonable if physicians (less than 3 weeks)
are present in the ambulance or if well-organized EMS systems are • Recent (within 2 to 4 weeks) internal bleeding
• Noncompressible vascular punctures
in place and meet the following criteria: (1) paramedics are full • For streptokinase/anistreplase: prior exposure (more than 5 days ago) or
time employees, can transmit 12-lead ECGs, and have initial and prior allergic reaction to these agents
ongoing training in ECG interpretation and STEMI treatment; • Pregnancy
(2) an online medical command and a medical director with train- • Active peptic ulcer
• Current use of anticoagulants: the higher the INR, the higher the risk of
ing/experience in STEMI management are available; and (3) bleeding
an ongoing continuous quality-improvement program has been
2
implemented (Class IIa, level of evidence: B). If the EMS are ca-
*Viewed as advisory for clinical decision making and may not be all-inclusive or defini-
pable of providing fibrinolysis, and if the patient qualifies for fib- tive.
† Could be an absolute contraindication in low-risk patients with STEMI.
rinolytic therapy, fibrinolysis should begin within 30 minutes of AVM, arteriovenous malformation; SBP, systolic BP; DBP, diastolic BP; CPR,
EMS arrival on scene. 3 cardiopulmonary resuscitation; INR, international normalized ratio.
Antman, JL., Anbe, DT., Armstrong, PW., et al. (2004). ACC/AHA Guidelines for the
Fibrinolytic Agents Management of Patients with ST-elevation Myocardial Infarction: A report of the
American College of Cardiology/American Heart Association task force on Practice
There are two major categories of fibrinolytic agents: fibrin nons-
Guidelines (writing Committee to Revise the 1999 Guidelines for the Management
elective and fibrin selective. A summary of the most commonly of Patients with Acute Myocardial Infarction). JACC, e3–e170.