Optimal thrombolytic strategies for acute myocardial infarction--bolus administration.

Optimal strategies for thrombolysis in myocardial infarction (TIMI) are still being sought because the TIMI 3 flow rates achievable using standard regimens average approximately 60%. Double bolus administration of recombinant tissue plasminogen activator (tPA) is a novel approach with potential for earlier patency combined with ease of administration. We reviewed total patency rates, TIMI 3 patency rates, mortality, stroke and intracranial haemorrhage rates in the major trials of accelerated infusion tPA/bolus tPA/reteplase in acute myocardial infarction. A direct comparison was performed with results of two recent trials of double bolus (two 50 mg boli, 30 min apart) vs. accelerated infusion tPA: the Double Bolus Lytic Efficacy Trial (DBLE), an angiographic study, and the COBALT Trial, a mortality study. The DBLE trial showed equivalent patency rates for accelerated infusion and double bolus administration of tPA. Reviewing other angiographic trials, total patency and TIMI 3 patency rates achievable with double bolus tPA were comparable to those with accelerated infusion tPA or bolus reteplase administration. The COBALT study demonstrated a 30-day mortality of 7.53% in patients treated with accelerated infusion tPA compared with 7.98% for double bolus tPA treated patients. The small excess in mortality with double bolus treatment was confined to the elderly; in those < or = 75 years, mortality rates were 5.6% and 5.7%, for double bolus and accelerated infusion, respectively, and rates for death or non-fatal stroke were 6.35% and 6.3%, respectively. Comparison with other trials demonstrated mortality, stroke and intracranial haemorrhage rates with double bolus treatment similar to those associated with either accelerated infusion tPA or bolus reteplase treatment. Double bolus administration of tPA to patients with acute myocardial infarction is associated with total patency, TIMI 3 patency, mortality, stroke and intracranial haemorrhage rates similar to those associated with either accelerated infusion of tPA or bolus reteplase.