VASCULAR BASIS FOR THE TREATMENT OF ISCHEMIA

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The activity of myocardial ischemia is used to assess risk and manage patients with coronary artery disease. The presence and severity of ischemia raises fundamentally important questions about how to treat this problem and reduce the occurrence of adverse outcomes. Pilot studies are in progress evaluating the effectiveness of standard anti-anginal therapies (drugs and revascularization). however, in patients with coronary atherosclerosis, risk factors such as plasma LDL and oxidized LDL are now known to impair endothelial function leading to loss of vasodilation, abnormal vasoconstriction, a procoagulant surface, and adhesion of inflammatory cells. Clinical research has shown that these dysfunctions are important causes of myocardial ischemia in patients with obstructive coronary artery disease. Therefore, we plan to test the hypothesis that athe aggressive treatment of plasma LDL and oxidized LDL will; (a) result in important improvements in the activity of ischemia in patients with coronary artery disease, and (b) reverse characteristic cell/vessel wall dysfunctions in the arteries of these patients with atherosclerosis. We plan a prospective randomized, double-blind, placebo-controlled, parallel design trial in patients with coronary artery disease, active myocardial ischemia and raised plasma LDL. Ambulatory ECG monitoring and ultrasonic examination of endothelium-dependent vasomotion of the brachial artery will both be used to measure athe activity of ischemia and arterial dysfunction at base-line and after 12 months of therapy with (1) standard diet (Control Group), (ii) standard diet plus lovastatin (LDL lowering strategy), and (iii) standard diet, lovastatin and probucol (LDL and oxidized LDL lowering strategy). Pilot studies and preliminary data are presented in support of this proposal. The goals of this project are to test the value of new therapies aimed at treating the vascular dysfunctions that characterize coronary atherosclerosis in an attempt to control the ischemia that is associated with increased risk of adverse outcomes. If this alternative to the present massive use of standard anti-anginal drugs an revascularization proves effective, it would likely have important implications for strategies aimed at control of adverse events affecting patients with coronary artery disease.