Initiate thrombolytic therapy for patients not referred to direct percutaneous revascularization.

Four current thrombolytic agents, include:

1. Alteplase (tPA) (100 mg maximum): 15 mg IV bolus, then 0.75 mg/kg over 30 minutes, then 0.5 mg/kg over the next 60 minutes.
2. Reteplase (rPA): 10 U over 2 minutes, followed by a second 10 U IV bolus 30 minutes later.
3. Streptokinase: 1.5 million units (MU) IV over 60 minutes.
4. Tenectaplase: IV bolus weight adjusted (30 mg to patients who weigh <60 kg, 35 mg to patients who weigh 60 kg to 69.9 kg, 40 mg to patients who weigh 70 kg to 79.9 kg, 45 mg to patients who weigh 80 kg to 89.9 kg, and 50 mg to patients who weigh >90 kg).

Thrombolytic agents should be started in the emergency room as mortality is directly related to time to reperfusion. Once thrombolytic agents are initiated, patients may be transferred to an intensive care unit/cardiac care unit (ICC/CCU).

DISCUSSION

Streptokinase, alteplase, and reteplase have all been shown to improve mortality rates following an AMI, when compared to placebo (ISIS-2, 1988; GUSTO-I, 1993a; and GUSTO-III, 1997). The original GUSTO trial suggested that use of alteplase resulted in a lower mortality rate than use of streptokinase with subcutaneous heparin (6.3% versus 7.2%). These results are most likely related to the improved TIMI grade-3 flow at 90 minutes for alteplase, as compared to streptokinase (GUSTO, 1993b).

GUSTO-I suggested that patients who benefit most from alteplase, in comparison with streptokinase, present within three hours of an acute anterior wall MI and are at low risk for intracranial hemorrhage. Streptokinase, on the other hand, is significantly less expensive than either alteplase or reteplase. Reteplase, when compared to alteplase, did not show a survival advantage, although its longer half-life allows for a bolus infusion (GUSTO III, 1997). Both reteplase and tenecteplase may be preferred over alteplase because of their ease of administration when compared to alteplase.

When using alteplase, reteplase, or tenecteplase, intravenous heparin is required for 48 hours (APTT goal 50 to 75 seconds). Patients treated with streptokinase should be given heparin (7,500 U) twice a day, unless they are at high-risk for systemic emboli. If they are at high risk for systemic emboli (large or anterior wall MI, atrial fibrillation, previous embolus, or known LV thrombus), intravenous heparin may be given.