CARDIAC RUPTURE ASSOCIATED WITH THROMBOLYTIC THERAPY - IMPACT OF TIMETO TREATMENT IN THE LATE ASSESSMENT OF THROMBOLYTIC EFFICACY (LATE) STUDY

Objectives. This prospective ancillary study was conducted to determin e the association between the time from symptom onset to treatment and cardiac rupture in patients with acute myocardial infarction. Backgro und. There is strong evidence that the time window for thrombolytic th erapy should be extended to at least 12 h; however, many clinicians ar e concerned that late treatment may cause an excessive occurrence of d eath from cardiac rupture. Because up to 30% of patients with acute my ocardial infarction arrive in the hospital >6 h from symptom onset, re solving this issue is of paramount clinical importance. Methods. A tot al of 5,711 patients with acute myocardial infarction were randomized to receive intravenous recombinant tissue-type plasminogen activator ( rt-PA) (100 mg over 3 h) or matching placebo, within 6 and 24 h from s ymptom onset. Both groups received immediate oral aspirin, and a major ity of patients received intravenous heparin during the initial 48 h. Results. By 35 days, 177 patients had died, with the cause of death sp ecified as cardiac rupture (53 patients), electromechanical dissociati on (42 patients) or asystole (82 patients). An additional 370 patients had died of other causes. In patients treated within 12 h, the propor tion of rupture deaths in the group given rt-PA was higher than that o bserved in those who received placebo, but the difference was not stat istically significant. In patients treated after 12 h, there was no ev idence of an increased incidence of rupture with rt-PA, and the propor tion of deaths due to rupture in this group was lower than that in pat ients given placebo. However, there was evidence of a difference betwe en rt-PA and placebo with respect to the time that rupture became clin ically manifest (treatment by time to death interaction, p = 0.03). Co nclusions. This study provides unequivocal evidence that late treatmen t (6 to 24 h after symptom onset) with rt-PA is not associated with an increased risk of cardiac rupture. However, for reasons that are uncl ear, coronary thrombolysis appears to accelerate rupture events, typic ally to within 24 h of treatment.