The use of tissue-type plasminogen activator for acute myocardial infarction in the elderly: Results from thrombolysis in myocardial infarction phase I, open label studies and the thrombolysis in myocardial infarction phase II pilot study

AbstractThe impact of age on hospital mortality, incidence of major hemorrhagic events and transfusion requirements was examined in 756 patients with acute myocardial infarction enrolled in the Thrombolysis in Myocardial Infarction (TIMI) Phase I, open label studies and the TIMI Phase II pilot study. The mortality rate significantly increased with age and was 3.5%, 11.5% and 12% in patients <65, 65 to 69 and 70 to 76 years of age, respectively (p < 0.001). Logistic regression analyses selected female gender, diabetes mellitus, extensive coronary artery disease, history of congestive heart failure, continuing chest pain immediately after recombinant tissue-type plasminogen activator (rt-PA) administration, low systolic blood pressure at the time of admission and advanced age as variables predictive of in-hospital death.The incidence of major hemorrhagic events among patients not undergoing cardiac surgery during hospitalization was 8.7%, 14.5% and 24.7% in patients aged <65, 65 to 69 and ⩾ 70 years, respectively (p < 0.001). The majority of hemorrhages were secondary to cardiac catheterization or puncture wounds. Variables related to a major hemorrhagic event included protocol, age, rt-PA dose/kg body weight and elevated diastolic blood pressure on admission. Of five intracranial bleeding events, three occurred in patients >65 years. Transfusion requirements significantly increased with age (p < 0.001). Reperfusion status at 90 min in the TIMI Phase I and open label studies A to C was similar in the three age groups studied and ranged from 60% to 71%a.Thus, a strategy of early cardiac catheterization in older patients with acute myocardial infarction treated with thrombolytic therapy is associated with an increased hospital mortality rate and incidence of bleeding compared with findings in younger patients. A randomized placebocontrolled trial appears to be needed to determine safety and efficacy of rt-PA therapy in patients >76 years