The applicants are a group of 22 clinical units (45 hospitals), 5 core laboratories, and a data coordinating center, most of whom participated in the TIMI I and TIMI II studies, whose 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 """"""""Thrompolysis in Myocardial Ischemia"""""""" (TIMI III), will utilize the expertise gained in the applicants' prior work with t-PA and PTCA for Q-wave MI, to determine the value of these new approaches for the related conditions of unstable angina and non-Q-wave MI--disorders which afflict approximately one million individuals annually in the United States. The group will conduct 2 randomized, blinded studies (TIMI IIIA and IIIB) directed toward two specific aims: (1) To determine if t-PA produces improvement in angiographically determined myocardial perfusion or coronary stenosis (TIMI IIIA); and, (2) to identify the optimal initial and follow-up management strategy (TIMI IIIB). Initially, is heparin, t-PA and/or t-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? TIMI IIIA will be conducted by a group of 13 clinical units which will randomize 300 patients over a 9-month period. The effect of t-PA on angiographically determined coronary artery blood flow and stenosis will be determined by a Core Laboratory of Quantitative Angiography. TIMI IIIB will be conducted by 21 clinical units, which will randomize 2,000 patients over a 2-year period. Success of therapy will be judged by the number of patients who do not experience death, MI, disabling stroke, or failure of therapy (defined as significant recurrent ischemic pain at rest, or unsatisfactory results of Holter monitoring or an ETT with thallium). Core Laboratories for ECG/ETT analysis, qualitative angiography, ambulatory ECG, and radionuclide (thallium) studies will assure quality of data collection and provide centralized, blinded analysis of crucial endpoint data. The sample will be of sufficient size to establish clearly the risks versus benefits of heparin therapy, t-PA therapy and t-PA plus heparin therapy, as well as the value of routine angiography followed by revascularization, for these serious and frequent disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL042311-02
Application #
3360423
Study Section
Special Emphasis Panel (SRC (MD))
Project Start
1989-04-01
Project End
1992-11-30
Budget Start
1990-12-20
Budget End
1991-11-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Solomon, D H; Stone, P H; Glynn, R J et al. (2001) Use of risk stratification to identify patients with unstable angina likeliest to benefit from an invasive versus conservative management strategy. J Am Coll Cardiol 38:969-76
Cannon, C P; McCabe, C H; Stone, P H et al. (1997) Circadian variation in the onset of unstable angina and non-Q-wave acute myocardial infarction (the TIMI III Registry and TIMI IIIB). Am J Cardiol 79:253-8
Cannon, C P; McCabe, C H; Stone, P H et al. (1997) The electrocardiogram predicts one-year outcome of patients with unstable angina and non-Q wave myocardial infarction: results of the TIMI III Registry ECG Ancillary Study. Thrombolysis in Myocardial Ischemia. J Am Coll Cardiol 30:133-40
Hochman, J S; McCabe, C H; Stone, P H et al. (1997) Outcome and profile of women and men presenting with acute coronary syndromes: a report from TIMI IIIB. TIMI Investigators. Thrombolysis in Myocardial Infarction. J Am Coll Cardiol 30:141-8
Anderson, H V; Gibson, R S; Stone, P H et al. (1997) Management of unstable angina pectoris and non-Q-wave acute myocardial infarction in the United States and Canada (the TIMI III Registry). Am J Cardiol 79:1441-6
Kleiman, N S; Anderson, H V; Rogers, W J et al. (1996) Comparison of outcome of patients with unstable angina and non-Q-wave acute myocardial infarction with and without prior coronary artery bypass grafting (Thrombolysis in Myocardial Ischemia III Registry). Am J Cardiol 77:227-31
Stone, P H; Thompson, B; Anderson, H V et al. (1996) Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: The TIMI III registry. JAMA 275:1104-12
Antman, E M; Tanasijevic, M J; Thompson, B et al. (1996) Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 335:1342-9
Cannon, C P; Thompson, B; McCabe, C H et al. (1995) Predictors of non-Q-wave acute myocardial infarction in patients with acute ischemic syndromes: an analysis from the Thrombolysis in Myocardial Ischemia (TIMI) III trials. Am J Cardiol 75:977-81
Anderson, H V; Cannon, C P; Stone, P H et al. (1995) One-year results of the Thrombolysis in Myocardial Infarction (TIMI) IIIB clinical trial. A randomized comparison of tissue-type plasminogen activator versus placebo and early invasive versus early conservative strategies in unstable angina and non-Q wave J Am Coll Cardiol 26:1643-50

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