Intravenous NPA for the treatment of infarcting myocardium early. InTIME-II, a double-blind comparison of single-bolus lanoteplase vs accelerated alteplase for the treatment of patients with acute myocardial infarction

Aims To compare the efficacy and safety of lanoteplase, a single-bolus thrombolytic drug derived from alteplase tissue plasminogen activator, with the established accelerated alteplase regimen in patients presenting within 6h of onset of ST elevation acute myocardial infarction. Methods and Results 15078 patients were recruited from 855 hospitals worldwide and randomized in a 2:1 ratio to receive either lanoteplase 120KU.kg−1as a single intravenous bolus, or up to 100mg accelerated alteplase given over 90min. The primary end-point was all-cause mortality at 30 days and the hypothesis was that the two treatments would be equivalent. By 30 days, 6·61% of alteplase-treated patients and 6·75% lanoteplase-treated patients had died (relative risk 1·02). Total stroke occurred in 1·53% alteplase- and 1·87% lanoteplase-treated patients (ns); haemorrhagic stroke rates were 0·64% alteplase and 1·12% lanoteplase (P=0·004). The net clinical deficit of 30-day death or non-fatal disabling stroke was 7·0% and 7·2%, respectively. By 6 months, 8·8% of alteplase-treated patients and 8·7% of lanoteplase-treated patients had died. Conclusion Single-bolus weight-adjusted lanoteplase is an effective thrombolytic agent, equivalent to alteplase in terms of its impact on survival and with a comparable risk-benefit profile. The single-bolus regimen should shorten symptoms to treatment times and be especially convenient for emergency department or out-of-hospital administration.