Tissue-Type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events (MACE) in Patients With Non-critical Coronary Artery Disease
Coronary artery disease is the leading cause of death in USA. Contemporary cardiac care has substantially reduced mortality and morbidity in patients with severe coronary artery disease. However, patients with mild to moderate coronary artery stenosis (<70% stenosis) often present in the future with life threatening acute coronary syndrome which carries significant mortality and morbidity. It is difficult to predict outcomes in these patients before the events because the lack of complete understanding of the mechanisms underlying acute coronary syndrome and the lack of reliable markers that will predict major adverse cardiac events (MACE). Tissue-type plasminogen activator (t-PA) is released from endothelial cells and a major factor that prevent thrombosis in the coronary artery, the cause of acute coronary syndrome. Endothelial dysfunction impairs t-PA release. Therefore, we hypothesize that patients with impaired coronary artery t-PA release will have significantly higher risk for future MACE due to intrinsic fibrinolytic dysfunction that leads to increased thrombosis risk.
To test this hypothesis, we will determine whether intrinsic endothelial fibrinolytic dysfunction predicts MACE in patients with non-significant CAD. The study will measure t-PA release mediated by bradykinin, a major mediator for t-PA release. This will involve infusion of bradykinin into left main coronary artery of individuals who have undergone routine cardiac catheterization (clinically indicated). We will take blood samples from the coronary sinus and measure t-PA and plasminogen activator inhibitor-1 antigen and activity levels.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||The Intracoronary Tissue-type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events in Patients With Non-critical Coronary Artery Disease|
- Mortality [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2003|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Bradykinin, 0.2 ug - 2ug/minute, one time intracoronary infusion over 6 minutes. Drug (bradykinin) will be infused into the left main coronary artery via diagnostic catheter (JL4) at an escalating rate of 0.2, 0.6, 2 g/ml (1ml/min). A 5F Multipurpose catheter will be advanced to coronary sinus for blood sampling.
Other Name: Bachem Distribution Services GmbH-Bradykinin
Please refer to this study by its ClinicalTrials.gov identifier: NCT00868855
|United States, Tennessee|
|Vanderbilt University Medical Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Douglas Vaughn, MD||Northwestern University|