Ancillary Studies in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial: Synergies and Opportunities
Section snippets
The Value of Ancillary Studies
Several types of ancillary studies are being performed in conjunction with the BARI 2D trial. One comprises substudies designed to address mechanistic questions that focus on a particular segment of the parent study population or on patients from a subset of clinical sites participating in the parent study. In another type of ancillary study, results are obtained from a single center or a subset of centers by using already collected data or new assays of stored blood or urine samples with
The prominence of procoagulation in diabetes
Impaired fibrinolysis has been implicated as a contributor to acceleration of CAD in type 2 diabetes, attributable to elevated blood concentrations of the primary physiologic inhibitor of fibrinolysis, plasminogen activator inhibitor–1 (PAI-1).3 Impaired fibrinolysis is thought to potentiate persistence of microthrombi and their propensity to initiate and sustain intense thrombosis. Activation of the coagulation system leads to the generation of thrombin and fibrinopeptide A (FPA), released
BARI 2D Ancillary Studies Addressing These Phenomena
Several BARI 2D ancillary studies23 are designed to determine whether inflammation, procoagulation, and progression of CAD, independently or in combination, are ameliorated in patients with type 2 diabetes who are treated with insulin-sensitizing regimens, insulin-providing regimens, or both. Another is designed to delineate the effects of the 2 insulin treatment regimens on the progression of coronary vasculopathy and cardiac events associated with diabetes with respect to expression of PAI-1.
Significance
Reduction of the toll due to CAD in the >16 million Americans thought to have type 2 diabetes will, perhaps, best be achieved by preventing and retarding the evolution of lesions into the vulnerable atherosclerotic plaques that may rupture and precipitate acute coronary syndromes. Through identification of specific mediators of the development of such plaques and targeting them for prophylactic pharmacologic intervention, morbidity and mortality may be ameliorated. The possibility that
References (23)
- et al.
Usefulness of fibrinogenolytic and procoagulant markers during thrombolytic therapy in predicting clinical outcomes in acute myocardial infarction
Am J Cardiol
(1996) - et al.
Hypercoagulability and high lipoprotein (a) levels in patients with type II diabetes mellitus
Atherosclerosis
(1996) - et al.
Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level and relative body weight in normal and obese subjects
Metabolism
(1986) - et al.
Platelet function, coagulopathy, and impaired fibrinolysis in diabetes
Cardiol Clin.
(2004) - et al.
Effects of increased concentrations of glucose on platelet reactivity in healthy subjects and in patients with and without diabetes mellitus
Am J Cardiol
(2003) - et al.
Burgeoning dilemmas in the management of diabetes and cardiovascular diseaserationale for the BARI 2D trial
Circulation
(2003) A perspective on the three large multicenter randomized clinical trials of coronary bypass surgery for chronic stable angina
Circulation
(1985)- et al.
Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients
Diabetes
(1994) - et al.
Fibrinopeptide-A as thrombotic risk marker in diabetic and atherosclerotic coronary vasculopathy
J Med
(1992) - et al.
Chronic subclinical inflammation as part of the insulin resistance syndromethe Insulin Resistance Atherosclerosis Study (IRAS)
Circulation
(2000)
5-Year incidence of atherosclerotic vascular disease in relation to general risk factors, insulin level, and abnormalities in lipoprotein composition in non-insulin-dependent diabetic and nondiabetic subjects
Circulation
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The core laboratories for electrocardiography (Dr. Bernard Chaitman, St. Louis University), economics (Dr. Mark A. Hlatky, Stanford University), and fibrinolysis (Dr. Burton E. Sobel, University of Vermont) were funded, respectively, by Grant Nos. U01 HL061746, U01 HL061748, and U01 HL063804 from the National Heart, Lung, and Blood Institute. The Nuclear Cardiology Core Laboratory (Dr. Ami E. Iskandrian, University of Alabama at Birmingham) received funding from Astellas Pharma US, Inc.