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)

Platelet-mediated coronary thrombosis is the primary pathophysiologic mechanism of acute coronary syndromes (ACS) and acute ischemic complications of percutaneous coronary intervention (PCI). The final common pathway of platelet aggregation that leads to thrombotic occlusion of coronary arteries involves cross-linking of receptor glycoprotein (GP) IIb-IIIa on adjacent platelets by adhesive plasma proteins, primarily fibrinogen. Clinical trials of several GP IIb-IIIa inhibitors have demonstrated an unequivocal clinical benefit of this potent antithrombotic therapy in patients with ACS as well as in those undergoing PCI. Nevertheless, a significant number of patients with ischemic heart disease may still be expected to require elective or emergency coronary artery bypass graft (CABG) after treatment with GP IIb-IIIa inhibitors. In the emergency CABG setting, complications and platelet blockade with GP IIb-IIIa inhibitors may further enhance the already heightened risk of bleeding as compared with elective procedures. This issue became apparent in the first large clinical trial of the GP IIb-IIIa inhibitor abciximab (c7E3 Fab, ReoPro((R)); Centocor, Malvern, Pa, and Eli Lilly and Co, Indianapolis, Ind) in patients undergoing high-risk PCI. In this study, mortality rates and bleeding complications were increased among patients undergoing emergency CABG after treatment with a bolus plus infusion of abciximab. Subsequent clinical experience also suggests that the potential for bleeding complications related to emergency CABG may be increased in patients treated with abciximab, particularly if the drug is discontinued within 6 hours of the operation. Higher bleeding risk with abciximab is a result of its prolonged antiplatelet effect, which is in contrast to the readily reversible platelet blockade provided by more recently developed small-molecule GP IIb-IIIa inhibitors such as the peptide eptifibatide (Integrilin((R)); COR Therapeutics, South San Francisco, Calif, and Key Pharmaceuticals, Kenilworth, NJ) and the nonpeptide tirofiban HCl (MK-383, Aggrastat((R)); Merck & Co, Whitehouse Station, NJ). Therefore, among patients requiring CABG after treatment with GP IIb-IIIa inhibitors, eptifibatide and tirofiban may be associated with fewer bleeding episodes than is abciximab. With recent approval of eptifibatide for patients with ACS and those scheduled for PCI and of tirofiban for patients with ACS, the number of patients receiving GP IIb-IIIa inhibitor therapy who subsequently undergo CABG is expected to increase significantly. Strategies for improved management of bleeding complications in these patients, including the choice of a GP IIb-IIIa inhibitor, are clearly needed and are discussed in detail.
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PMID:Safety of glycoprotein IIb-IIIa inhibitors: A heart surgeon's perspective. 1050 36

The American College of Cardiology/American Heart Association Task Force on Practice Guidelines has published recommendations on the diagnosis and treatment of patients with known or suspected unstable angina and non-ST-segment elevation myocardial infarction. The acute ischemia pathway presented in these guidelines encompasses both an early invasive strategy and an early conservative strategy. There are now 4 randomized, controlled trials that have compared the routine early invasive strategy with the selective-invasive or ischemia-guided strategy (Thrombolysis in Myocardial Infarction [TIMI] IIIB, Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital [VANQWISH], Fragmin and Fast Revascularization During Instability in Coronary Artery Disease [FRISC] II, and Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy [TACTICS]-TIMI 18). The most relevant of these studies to current clinical practice are the FRISC II and TACTICS-TIMI 18 studies. The data from these studies indicate that ST-segment depression or elevated levels of troponin or the MB isoenzyme of creatinine kinase are markers of increased risk and that such patients would benefit from early revascularization. However, the data further suggest that aggressive antiplatelet, antithrombin, and anti-ischemic therapies are also important. Although FRISC II and TACTICS-TIMI 18 support an early invasive approach in most patients (ie, intermediate- and high-risk patients) with non-ST-segment elevation acute coronary syndromes (ACS), all 4 trials support a more conservative approach in those without electrocardiographic changes or enzyme elevations, notably the use of intensive antiplatelet, antithrombotic, and anti-ischemic therapy combined with careful clinical assessment and provocative testing. Patients then undergo catheterization and revascularization only if spontaneous angina occurs or if there is electrocardiographic, enzymatic, or other objective evidence of stress-induced myocardial ischemia. We conclude that tailoring the early initial therapy in hospital to the level of risk is essential to optimizing efficacy and clinical outcomes in this challenging, but common group of ACS patients.
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PMID:Interpreting new treatment guidelines for non-ST-segment elevation acute coronary syndromes. 1169 15

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

Patients presenting with unstable angina pectoris or non-Q-wave myocardial infarction (MI), if treated inadequately, are at a high risk of MI and subsequent mortality. The use of intravenous small molecule glycoprotein IIb/IIIa inhibitors along with standard therapeutic management options improves outcome. Since the publication of the Thrombolysis in Myocardial Ischemia IIIB, Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) and Fragmin and Fast Revascularization during InStability in Coronary artery disease II (FRISC II) studies, there is great debate about the advantages of following an early 'invasive' treatment option with coronary angiography and revascularization after initial medical therapy compared with the 'conservative' approach, where angiography is reserved for those who remain symptomatic. The Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy--Thrombolysis in Myocardial Infarction 18 (TACTICS-TIMI 18) study has helped to resolve some of the controversies since it was designed with more current medical (early and routine use of tirofiban) and revascularization (use of stents during percutaneous coronary interventions) options as part of the invasive treatment protocol. This study indicated that an early invasive strategy in risk stratified patients combined with early use of tirofiban with standard medical therapy significantly improves outcome and appears well tolerated.
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PMID:Current management of unstable angina: lessons from the TACTICS-TIMI 18 trial. 1472 69