The applicants are the Coagulation Core Laboratory (CCL) from the TIMI II clinical trial. Together with 22 clinical units, 5 core laboratories and a data coordinating center their long term objective is to resolve the major controversial issues currently complicating the management of patients with unstable angina and non-Q-wave MI. The proposed study, entitled """"""""Thrombolysis in Myocardial Ischemia"""""""" (TIMI III) will utilize the expertise gained in the applicants prior work with TIMI II and the TAMI trials. The group will conduct 2 randomized, blinded studies (TIMI III A and III B) directed toward two specific aims: 1) to determine if rt-PA produces improvement in angiographically determined myocardial perfusion or coronary stenosis (TIMI III A); and 2) to identify the optimal initial and follow-up management strategy (TIMI III B). Initially, is heparin, rt-PA and/or rt-PA plus heparin superior to the addition of placebo to conventional therapy? In follow-up, is there a need for routine angiography followed, if the anatomy is suitable, by revascularization. Within the context of this study the rationale of the CCL is that analysis of the molecular events of coagulation and fibrinolysis in TIMI III will increase our understanding of fundamental mechanisms of disease and yield clinically useful information. Therefore, the major objective of this proposal is to assay relevant components of the coagulation and fibrinolytic systems in patients entered into the different therapeutic arms of TIMI III. The second objective is to correlate changes in these hemostatic parameters with the primary and secondary endpoints of TIMI III. The third objective will be to establish and maintain a plasma sample repository for future analyses.
