Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The key role of platelets in the pathogenesis of ischemic heart disease has led to the development of new classes of agents to control platelet function. The platelet glycoprotein IIb/IIIa receptor mediates the final common pathway to platelet aggregation. Drugs that block the glycoprotein IIb/IIIa receptor potently inhibit platelet aggregation. Monoclonal antibodies, cyclic peptides, and peptide-derivative glycoprotein IIb/IIIa inhibitors have been developed. The monoclonal antibody Fab fragment, chimeric 7E3, has been shown to significantly reduce ischemic complications and clinical restenosis after high-risk angioplasty in the large-scale Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) trial. A number of glycoprotein IIb/IIIa inhibitors have been tested in patients with unstable angina with similarly positive results, and initial trials in patients with acute myocardial infarction are also encouraging. Further evaluation of these agents in large scale trials is currently underway and should help determine the place and appropriate use of these agents in the clinical arena.
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PMID:Platelet glycoprotein IIb/IIIa receptor inhibitors in ischemic heart disease. 754 85

In the primary prevention of arterial disease, there may be a role for anti-oxidant vitamins and for oestrogen replacement therapy in postmenopausal women. For the secondary prevention of thrombotic complications of atherosclerosis, aspirin has proven efficacious in reducing both mortality and morbidity. Patients with ischaemic heart disease and moderately elevated serum cholesterol benefit from simvastatin administration. Heparin and oral anticoagulants are the mainstay in the primary and secondary prevention of venous thrombosis. More potent antithrombotic compounds, the direct thrombin inhibitors and the glycoprotein IIb-IIIa antagonists, are mainly being evaluated in emergency coronary medicine. Preliminary results are encouraging but haemorrhagic problems need to be solved. The trend toward a decrease in late restenosis following coronary angioplasty using a IIb-IIIa antagonizing Fab fragment may prove to be a major therapeutic breakthrough.
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PMID:Clinical trials of primary and secondary prevention of thrombosis and restenosis. 857 89

We report here a case of a patient who underwent percutaneous intervention to the left anterior descending artery, complicated by thrombus formation within the myocardial bridge distal to the lesion. There was complete angiographic resolution of thrombus and restoration of the normal antegrade blood flow after infusion of glycoprotein IIb/IIIa antagonist (abciximab). Our observation may suggest that the presence of myocardial bridging distal to coronary lesions should be considered seriously in preprocedural evaluation of the lesions as a potential risk factor for intracoronary thrombus formation. The main coronary arteries and the proximal segments of their major branches lie free on the epicardial surface of the heart. However, in some instances these vessels may penetrate into the muscle being surrounded by the myocardium, with the overlying muscle referred to as a "bridge". Myocardial bridging appears to be a congenital anomaly, due to failure of exteriorization of the primitive coronary intratrabecular arterial network. It occurs in 5-86% of patients in autopsy studies, and it is observed as systolic coronary artery narrowing in 0.5-12% of patients undergoing coronary arteriography. Although the gross anatomist had long recognized that the epicardial coronary artery might on occasion course directly through a segment of cardiac muscle, the physiological significance of this phenomenon was considered benign. This is partly because traditional teaching concerning coronary blood flow delivery to the left ventricular myocardium emphasized the primacy of the diastolic phase of the cardiac cycle. However, myocardial bridging is not always a benign finding, with recent reports suggesting an association with myocardial ischemia, infarction, vasospasm, cardiac arrythmias, and sudden death.
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PMID:Stent procedure complicated by thrombus formation distal to the lesion within a muscle bridge. 947 97

The mechanisms of action of currently available and newer antiplatelet agents and evidence of the efficacy of antiplatelet agents for primary and secondary prevention of coronary artery disease are reviewed. Available data do not support the widespread use of aspirin for primary prevention of cardiovascular disease. Patients over the age of 50 years with at least one additional risk factor for coronary artery disease may benefit, although possibly at an increased risk of hemorrhagic stroke. Aspirin is recommended for secondary prevention of vascular disease in patients with stable or unstable angina, clinical or laboratory evidence of coronary artery disease, history of myocardial infarction, or history of stroke or transient ischemic attack. There are no data supporting a role for dipyridamole for primary or secondary prevention of ischemic heart disease. Abciximab has been shown to reduce the risk of cardiovascular complications at 30 days after percutaneous transluminal coronary angioplasty in patients with refractory unstable angina. Studies with other glycoprotein IIb/IIIa-receptor antagonists, including eptifibatide, tirofiban, and lamifiban, have yielded promising results. Ticlopidine may be used for secondary prevention of cardiovascular disease in patients with unstable angina who are allergic to or intolerant of aspirin. Clopidogrel has been shown to be safe and effective for secondary prevention of vascular events. Aspirin has a role in secondary prevention of coronary artery disease; among patients who are allergic to or intolerant of aspirin, ticlopidine has a role in patients with unstable angina and clopidogrel has a potential role in patients with ischemic heart or vascular disease.
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PMID:Antiplatelet therapy in coronary artery disease: review and update of efficacy studies. 978 97

Experiments were performed in rat models to study the effectiveness of various antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia. The time to the onset of ST-segment elevation and initiating ventricular arrhythmias, frequency and incidence of ventricular arrhythmias, and mortality rates were observed during acute myocardial ischemia (20 minutes) induced by ligation of the proximal left anterior descending coronary artery (LAD) in anesthetized rats. Four groups were studied: Control group (n = 10, not pretreated); Aspirin pretreated group (n = 10, 300 mg/kg p.o. for 1 wk); Ticlopidine pretreated group (n = 10, 200 mg/kg p.o. for 1 wk); and Abciximab (Platelet glycoprotein IIb/IIIa receptor antagonist) pretreated group (n = 10, 2 mg/kg i.v. 10-20 minutes before an experiment). No significant difference was observed in the time to the onset of ST-segment elevation and ventricular arrhythmias between the groups. The incidence of ventricular tachycardia (VT) in the abciximab group was significantly lower than in the control group (p < 0.05) and ventricular fibrillation (VF) in the aspirin and ticlopidine group was significantly lower than in the control group (p < 0.05). The mortality rate in the ticlopidine group was significantly lower than in the control group (p < 0.01). This study suggests aspirin, ticlopidine, and abciximab can effectively prevent VT or VF during acute myocardial ischemia induced by nonthrombotic occlusion and its antiarrhythmic effect may lead to prolonged survival.
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PMID:The effects of antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia in rats. 1037 Apr

Platelet glycoprotein IIb/IIIa inhibitors have been extensively studied in the treatment of patients with ischemic heart disease. Data regarding the use of these agents in the absence of concomitant intravenous heparin have been conflicting. We sought to determine, using propensity analysis, whether the benefit of eptifibatide, a IIb/IIIa inhibitor, in the treatment of acute coronary syndromes is affected by the concurrent administration of heparin. By trial design, patients were randomized to either eptifibatide or placebo, whereas use of intravenous heparin was left to the discretion of treating physicians. The effect of eptifibatide on the 30-day composite end point of death or myocardial infarction was studied in patients who received heparin and those who did not. Propensity analysis methods were used to control for confounding and presumed selection biases. Among 5,576 patients who were receiving heparin when the bolus dose of the study drug was administered, eptifibatide was associated with a reduced composite end point rate (13%) compared with that of placebo (14.5% vs 16.6%, p = 0.03). In contrast, among 1,441 patients who were not receiving heparin, there was no difference in 30-day event rates with eptifibatide compared with placebo (13.7% vs 13.1%, p > 0.7). After a propensity score for use of heparin was developed, however, use of heparin did not affect the reduced risk associated with eptifibatide (adjusted relative risk [RR] for heparin-eptifibatide interaction term 0.90, 95% confidence interval [CI] 0.61 to 1.32, p > 0.5), but the propensity for heparin use was a strong predictor of events (adjusted RR 1.76, 95% CI 1.42 to 2.17, p < 0.001). The use of eptifibatide independently predicted a lower risk of events (adjusted RR 0.31, 95% CI 0.10 to 0.93, p = 0.04). Thus, the apparent positive impact of heparin on the benefits of eptifibatide therapy was largely due to confounding and bias.
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PMID:Prognostic importance of concomitant heparin with eptifibatide in acute coronary syndromes. PURSUIT Investigators. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy. 1123 Aug 34

The incidence of cardiovascular diseases among diabetic patients is so high that diabetes mellitus is currently defined as a cardiovascular disease equivalent. Furthermore, diabetic patients who develop acute coronary syndromes have a poorer short-term and long-term prognosis, so primary and secondary preventive measures are critically important in this population subgroup. There is substantial evidence that pharmacological therapy for primary and secondary cardiovascular prevention is more effective in diabetic patients than in non-diabetics. This article reviews the evidence of the efficacy of pharmacological prevention therapies in diabetic patients in favor of an aggressive pharmacological preventive strategy. Every diabetic patient without known cardiovascular disease should be treated with angiotensin-converting enzyme inhibitors and statins. High-risk patients should also receive low-dose aspirin.Compared with non-diabetics, diabetic patients who develop acute coronary events benefit more from the addition of intensive antithrombotic therapy to aspirin treatment. Diabetic patients presenting with non-ST segment elevation syndromes have better outcomes when treated with clopidogrel or glycoprotein IIb/IIIa inhibitors, and diabetics presenting with ST-segment elevation or left bundle-branch block have a greater survival benefit when given thrombolytic therapy compared with non-diabetic patients.Unless formal contraindications are present, diabetic patients with ischemic heart disease, particularly those with previous myocardial infarction, should always be treated with aspirin, betablockers, angiotensin converting enzyme inhibitors, and statins, regardless of lipid levels, left ventricular systolic function or the presence of congestive heart failure.
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PMID:[Prevention and treatment of ischemic heart disease in patients with diabetes mellitus]. 1223 27

Conventional therapy for non-ST-segment elevation acute coronary syndrome (ACS) has traditionally employed an "ischemia-guided" strategy. In this approach, diagnostic cardiac catheterization and revascularization are only used in patients with objective evidence of myocardial ischemia as identified by recurrent symptoms or provocative stress testing. More recent studies, however, have demonstrated improved clinical outcomes with the use of an "early invasive" approach, employing routine coronary angiography early in the patient's hospital course, followed by percutaneous intervention or bypass surgery where appropriate. Improved clinical outcomes associated with an "early invasive" strategy may have evolved as a consequence of recent advances in both adjunctive pharmacotherapy and revascularization technique. In particular, use of glycoprotein IIb/IIIa inhibitors and/or low-molecular-weight heparin before catheterization have been shown to reduce clinical events in patients with ACS, and may reduce the risk of an invasive approach by plaque passivation before interventional therapy. Perhaps more importantly, the combined use of glycoprotein IIb/IIIa inhibitors and intracoronary stenting may reduce the potential early hazard of an invasive approach by specifically decreasing the incidence of death and nonfatal myocardial infarction associated with percutaneous intervention. In spite of the benefits of this synergistic combination of pharmacology and mechanical revascularization, risk stratification remains important in identifying high-risk individuals most likely to benefit from an "early invasive" approach. In addition, angiography with possible percutaneous coronary intervention of "culprit" lesions should always be used in combination with aggressive medical therapy to treat the widespread coronary atherosclerosis commonly seen in patients with ACS.
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PMID:"Ischemia-guided" versus "early invasive" strategies in the management of acute coronary syndrome/non-ST-segment elevation myocardial infarction: the interventionalist's perspective. 1264 47

Is a "routine invasive" or "selective invasive" strategy the best approach for patients with non-ST-segment elevation acute coronary syndrome (ACS)? A "selective invasive" strategy incorporates ischemia-guided use of aggressive medical therapy followed by angiography and revascularization for angina or stress-induced myocardial ischemia. The "routine invasive" strategy (cardiac catheterization followed by percutaneous coronary intervention within 24 to 48 h of symptom-onset) is frequently employed, but no randomized, controlled trials have demonstrated improved clinical outcomes. Recently, the second Fragmin and fast Revascularization during InStability in Coronary artery disease (FRISC-II) and the Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction (TACTICS TIMI-18) trials found significant reductions in death, recurrent myocardial infarction, or hospitalization for biomarker-positive ACS. Also, the third Randomized Intervention Trial of unstable Angina (RITA-3) recently reported a halving of refractory angina and reduction in the use of antianginal medication with early intervention. Early trials failed to demonstrate the superiority of the "routine invasive" approach, presumably because of fewer revascularizations, unavailability of stents, and more recent use of glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparins. The FRISC-II, TACTICS TIMI-18, and RITA-3 studies indicate that higher-risk patients benefit from early revascularization, but that aggressive antiplatelet, antithrombin, and anti-ischemic therapy are also important. While all three trials support an "early invasive" approach in intermediate- and high-risk patients, other trials support a more "conservative" approach in those without electrocardiographic changes or enzyme elevations. Optimal management should incorporate both strategies.
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PMID:"Routine invasive" versus "selective invasive" approaches to non-ST-segment elevation acute coronary syndromes management in the post-stent/platelet inhibition era. 1264 49

Atherosclerotic heart disease is the leading cause of death in patients with diabetes mellitus. Platelets play a major role in the clinical manifestations of ischemic heart disease. Diabetic patients have hyperreactive platelets with exaggerated adhesion, aggregation and thrombin generation. Antiplatelet agents, including aspirin, clopidogrel, and glycoprotein IIb/IIIa inhibitors, have shown significant efficacy in reducing recurrent ischemic events in patients with diabetes. Treatment with glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention reduces mortality in diabetic patients.
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PMID:Platelets and antiplatelet therapy in patients with diabetes mellitus. 1273 Jun 35


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