Late Assessment of Thrombolytic Efficacy (LATE) study with alteplase 6-24 hours after onset of acute myocardial infarction

Abstract

The effect of late thrombolysis in acute myocardial infarction (AMI)—ie, treatment beginning more than 6 h after the onset of symptoms—remains controversial. The Late Assessment of Thrombolytic Efficacy (LATE) study is a large randomised trial designed to resolve this question. 5711 patients with symptoms and electrocardiographic criteria consistent with AMI were randomised double-blind to intravenous alteplase (100 mg over 3 h) or matching placebo, between 6 and 24 h from symptom onset. Both groups received immediate oral aspirin and for later recruits intravenous heparin for 48 h was recommended. All patients were followed up for at least 6 months and 73% were followed up for 1 year. Intention-to-treat analysis of survival revealed a non-significant reduction in the alteplase group (397/2836 deaths) compared with placebo (444/2875). 35-day mortality was 8·86% and 10 31%, respectively, a relative reduction of 14·1% (95% Cl 0-28·1%). Pre-specified survival analysis according to treatment within 12 h of symptom onset, however, showed a significant reduction in mortality in favour of alteplase: 35-day mortality was 8 90% versus 11·97% for placebo, a relative reduction of 25 6% (p=0·0229, 95% Cl 6·3-45 0%). Rates were 8·7% and 9 2%, respectively, for those treated at 12-24 h but subgroup analysis suggests that some patients may benefit even when treated after 12 h. Although treatment with alteplase resulted in an excess of haemorrhagic strokes, by 6 months the number of disabled survivors was the same in both treatment groups and other clinical events were observed with similar frequency in the two groups. We conclude that the time window for thrombolysis with alteplase should be extended to at least 12 h from symptom onset in patients with AMI.