Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.2.1.1 (ACS)
78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this article we have outlined the current rationale and role of invasive management in ACS. For the majority of patients with ACS, who are either at high risk or unstable, invasive management is a critical element in breaking the sequence of recurrent ischemia leading to early cardiac events (Fig. 11). Secular trends in the care of cardiovascular patients predict even more sophisticated, invasive methods of treating coronary occlusion in the future. A futurist's view on this subject may envision the following type of scenario. A patient with prior CAD experiences persistent chest pain and notifies the emergency medical system. The paramedics arrive, and perform a rapid fingerstick cardiac biomarker panel and ECG. The results are interpreted by an emergency physician via a telecommunication system, and the patient is determined to be at high risk. He or she is triaged to a center capable of angioplasty and bypass surgery. On the way to the hospital, the patient is treated with aspirin, IV heparin, and an IV glycoprotein IIb/IIIa inhibitor. The patient undergoes triage angiography within 1 hour of hospital arrival, culprit lesion(s) are identified, and a revascularization plan is made--setting a critical pathway that is definitive. This vision is not far off on the horizon. We anticipate additional clinical trial results will help form the decision points in this optimal treatment scenario, which for a large proportion of patients will involve invasive management.
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PMID:Early use of coronary angiography and intervention. 1038 33

Transradial coronary angioplasty and stent implantation in have been associated with reduced complications, length of stay and hospital costs when compared to the transfemoral approach. Fourteen high-risk patients with acute myocardial infarction underwent transradial coronary angioplasty and stent placement. All diagnostic and interventional procedures were successfully completed using 6 French guide catheters and ACS Tristar stents (Guidant Corporation, Santa Clara, California) up to 4 mm in diameter. Thirteen patients received glycoprotein IIb/IIIa inhibitors. There were no procedural or access site complications. The mean length of stay was 3.5 days and the mean time interval from initial radial cannulation compared favorably with 14 acute myocardial infarction patients undergoing transfemoral angioplasty and stent placement. Transradial angioplasty in acute myocardial infarction appears to be a safe and feasible option. The procedure time is not increased in experienced hands, and the combination of rare access site complications and early ambulation may lead to decreased morbidity and lower costs. Transradial angioplasty in acute myocardial infarction may be an attractive option in thrombolytic therapy patients (facilitated percutaneous coronary intervention) or those who require aggressive anticoagulation or antiplatelet therapy.
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PMID:Transradial coronary angioplasty and stent implantation in acute myocardial infarction: initial experience. 1106 May 67

Optimized medical treatment for the non-ST segment elevation acute coronary syndromes (NSTE ACS) should consist of a combined antithrombotic/anti-anginal regimen. Standard antithrombotic treatment is currently unfractionated heparin and aspirin, and in high-risk patients glycoprotein IIb/IIIa inhibitors. However, low-molecular-weight heparins (LMWHs) have practical and clinical advantages over UFH and can be considered an effective alternative in the medical treatment of ACS and in patients proceeding to surgical interventions. Benefits include a more predictable and stable therapeutic response, no need for coagulation monitoring and a reduced incidence heparin-induced thrombocytopenia. In this context, the LMWH enoxaparin has demonstrated sustained clinical and economic benefits compared with UFH, with no increase in major bleeding complications. In addition, recently published studies indicate that LMWHs can improve reperfusion of the arteries and reduce reocclusion when used as adjunctive anticoagulant therapy in patients with ST segment elevation (STE) ACS undergoing thrombolysis with fibrin-specific agents or streptokinase.
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PMID:The role of low-molecular-weight heparin in the management of acute coronary syndromes. 1170 10

Non-ST segment elevation acute coronary syndrome (NSTE ACS) has a high rate of recurrence. Both antithrombotic and antiplatelet agents in association with coronary revascularization play an important role in the prevention of an adverse outcome. Acetylsalicylic acid, heparin and low molecular weight heparin (especially enoxaparin), and the intravenous small-molecule glycoprotein IIb/IIIa inhibitors, are of proven value. Recently, clopidogrel has been shown to reduce recurrent ischemic events, both early and during the first year after the index ACS. Furthermore, two recent trials have shown that an early invasive strategy is preferable to a conservative approach in the higher risk patient. As yet, no study has shown either the efficacy or the safety of combining all these treatment modalities in the management of the NSTE ACS patient. The initial choice of antithrombotic and antiplatelet agents and a strategy for early revascularization is made after considering the risk of recurrent acute ischemic events. For patients destined to have an early invasive strategy, it is desirable to choose an anti-thrombotic/antiplatelet combination that will reduce events before revascularization, enhance the revascularization procedure and not be associated with excessive bleeding. A risk-determined algorithm is presented, which applies observations made at the time of presentation to decide the optimal management for the individual patient.
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PMID:Preventing thrombosis: update of first-line therapy in the management of non-ST segment elevation acute coronary syndromes. 1246 82

The superiority of enoxaparin compared with unfractionated heparin in the medical management of patients with non-ST elevation acute coronary syndromes (NSTE ACS) has been demonstrated in clinical trials. Further, enoxaparin has been shown to be safe and effective during PCI, including in combination with glycoprotein IIb/IIIa inhibitors. Whether enoxaparin is superior to unfractionated heparin in patients with NSTE ACS under-going early invasive strategy is currently being tested in a large clinical trial. Data on the use of enoxaparin in patients undergoing primary angioplasty for ST-segment elevation myocardial infarction are limited. Unlike patients who present to the catheterization laboratory after several doses of enoxaparin where in a steady state anticoagulation might have been achieved, patients who present early after administration of a single dose of subcutaneous enoxaparin may not have an adequate level of anticoagulation for PCI. The ability to monitor activity of enoxaparin in such patients using a point-of-care test might be useful. This report describes a patient with ST-segment elevation myocardial infarction who presented for primary angioplasty 75 minutes after administration of subcutaneous enoxaparin. The Rapidpoint Enox test measured 135 seconds and the patient's corresponding serum anti-Xa level was 0.12 IU/mL indicating a suboptimal level of anticoagulation for PCI. Procedural success was attained using additional 0.3-mg/kg intravenous enoxaparin.
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PMID:Primary PCI for ST-segment elevation myocardial infarction in a patient treated with subcutaneous enoxaparin utilizing point-of-care Enox test. 1278 20

Coronary disease accounts for the majority of deaths among patients with diabetes and the thrombotic milieu accelerated by diabetes results in unstable angina (UA), non-ST segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial infarction (STEMI) or death. Upstream use of a glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor with percutaneous coronary intervention (PCI) as part of an early invasive approach is preferred. However substantial numbers of patients present to rural or non-teaching hospitals without immediate access to a catheterization laboratory. Enhanced GP IIb/IIIa receptor mobilization, TXA2 production and platelet activation together present an extensive thrombotic challenge that may not be overcome with current doses of GP IIb/IIIa inhibitors when used without PCI. Heterogeneity of platelet aggregometric analysis may have identified GP IIb/IIIa doses used in clinical trials that may not fully overcome the thrombotic challenge in patients with diabetes. GUSTO-IV ACS failed to demonstrate a difference in mortality when used without PCI. The PURSUIT trial provided evidence that eptifibatide decreases death or non-fatal myocardial infarction (MI) in the main group and in the diabetic subgroup. Reductions in this primary endpoint were driven by the reduction in non-fatal MI. The PRISM and PRISM-PLUS trials demonstrated a reduction in death, MI or refractory ischaemia at 48 h or 7 days in the main cohort but not specifically in patients with diabetes. Data supporting use of GP IIb/IIIa inhibitors are inconsistent, raising the question of whether these agents should be used at all without PCI. Variability in experimental methodology of platelet aggregometry and selection of anticoagulant used during dose finding studies may have generated doses that are insufficient to overcome the thrombotic burden. A new marker of active inflammation, sCD40L is found to be upregulated at subtherapeutic doses of GP IIb/IIIa inhibitors, suggesting that rebound inflammatory processes may partially account for absence of clear evidence of benefit with some GP IIb/IIIa inhibitors in patients with diabetes experiencing UA/NSTEMI.
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PMID:Selection of glycoprotein IIb/IIIa inhibitors for upstream use in patients with diabetes experiencing unstable angina or non-ST segment elevation myocardial infarction. What have we learned in the last 10 years? 1558 37

NSTE ACS is a clinically significant problem. Endothelial dysfunction triggered by traditional cardiovascular risk factors (and perhaps by other as yet unidentified risks) in the susceptible host leads to the formation and development of atherosclerotic plaque. Inflammatory mediators and mechanical stresses contribute to plaque rupture by disrupting the protective fibrous cap. In about 25% of patients who have ACS, typically those who are younger, female, or smokers, plaque erosion seems to be the main underlying pathologic mechanism. Endothelial alteration, inflammation,or exposure of the lipid core results in the release of TF, vWF, and PAF. The release of these factors leads to platelet activation and aggregation as well as to the formation of a fibrin clot, resulting in arterial thrombosis that occludes the vessel. A variety of factors, including circulating catecholamines, LDL levels, blood glucose levels, and systemic thrombogenic factors, can affect the extent and stability of the thrombus, thereby determining whether the occlusion is complete and fixed, labile and nonocclusive (NSTE ACS),or clinically silent resulting in a mural thrombus and plaque growth. The acute treatment of NSTEACS is directed at interrupting the prothrombotic environment surrounding the ruptured plaque; thus, antiplatelet agents such as aspirin, clopidogrel, and glycoprotein IIb/IIla receptor antagonists,as well as anticoagulants such as heparin, are the mainstays of early therapy.
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PMID:Pathogenesis and early management of non-ST-segment elevation acute coronary syndromes. 1632 54

International guidelines issued in recent years by the European Society of Cardiology and the American College of Cardiology/American Heart Association were aimed at presenting all the relevant evidence in the management of acute coronary syndromes and at helping physicians in routine clinical decision-making in order to weigh the benefits and risks of diagnostic or therapeutic procedures. A recent debate has been held in the scientific community about the correct interpretation of guidelines and the methods concerning the process of their implementation. Some of their limitations have been discussed as well. Many evidences collected in the guidelines are drawn by randomized clinical trials, some others by national and international surveys. The number of the surveys has rapidly increased in recent years, in both the international (ENACT, GRACE, Euro Heart Survey ACS, NRMI) and the Italian setting; some of these have been organized by the Italian Association of Hospital Cardiologists (ANMCO), either as national surveys (BLITZ-1 and BLITZ-2) or as regional or local registries (AI-CARE2, VENERE, GestIMA). In these reports a gap between the evidence-based recommendations of guidelines for acute coronary syndromes and actual clinical practice was documented. The lack of compliance with guidelines appears to be prevalent across a variety of medical conditions. The reluctance of physicians to apply the guidelines regarding the performance of an early invasive strategy, or the administration of glycoprotein IIb/IIIa inhibitors or thienopyridines is sometimes due to concerns that guidelines may not be valid in certain subsets of high-risk patients encountered in daily clinical practice or to inadequacy in the way care for acute coronary syndromes is delivered. Observational studies attempt to understand how clinical practice may be modified through continuous feedback. ANMCO, like other associations of cardiologists, is focusing its efforts on the improvement of the quality of care for acute coronary syndromes through educational interventions that target cardiologists involved in the care of patients, and on the improvement of the appropriate use of invasive cardiac procedures and other guideline recommendations mainly in high-risk patients.
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PMID:[How to match resources with appropriateness: lessons from the registries of the Italian Association of Hospital Cardiologists]. 1674 92

Thrombosis superimposed on arteriosclerosis is the principal cause of mortality and morbidity in patients with arteriosclerosis. The use of antiplatelet agents and anticoagulants in the treatment of arteriosclerosis is well established, based on many large randomized trials. Aspirin is indicated for primary prevention in patients at increased risk of developing symptomatic atherosclerotic vascular disease. For patients with known vascular disease, antiplatelet therapy with aspirin is a well-established treatment. For high-risk patients such as those with acute coronary syndromes (ACS; unstable angina, myocardial infarction), dual antiplatelet therapy with aspirin and clopidogrel is indicated, based on results of the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial. Platelet glycoprotein IIb/IIIa agents are powerful inhibitors of platelet function and are also effective in ACS, but the benefit is confined to high-risk patients. Anticoagulation with heparin or low-molecular-weight heparin (eg, enoxaparin) is also effective, with an approximately 50% reduction in cardiovascular events. These agents are also indicated for patients undergoing percutaneous coronary intervention. Prolonged dual antiplatelet therapy (at least 6 months) is recommended for patients receiving drug-eluting stents. The efficacy of antiplatelet therapy is thus well established in treating atherothrombosis, but aggressive therapy is associated with an increased bleeding risk. Newer agents may provide improved efficacy with a lower risk of bleeding.
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PMID:Use of antiplatelet agents and anticoagulants for cardiovascular disease: current standards and best practices. 1771 74

Antithrombotic and powerful antiplatelet therapies, in addition to early percutaneous coronary intervention (PCI) are considered the treatment of choice for moderate- to high-risk patients with acute coronary syndromes (ACS; unstable angina and non-ST-segment elevation myocardial infarction). However, despite the integration of newer therapies including stents, glycoprotein IIb/IIIa inhibitors (GPI), and thienopyridines, the rate of adverse ischemic events still remains unacceptably high. Intensive pharmacologic regimens used to stabilize the disrupted atherosclerotic plaque and support angioplasty as well as surgical revascularization procedures, elicit a high rate of bleeding complications. Recent trials (ACUITY and HORIZONS studies) added evidence regarding safety and efficacy of bivalirudin use in acute coronary syndromes. In summary, is has been shown that bivalirudin alone is safe and effective in the vast majority of patients suffering from acute coronary syndromes and being treated invasively. The cost-effectiveness of such an approach will have to be determined. It remains to be a matter of discussion whether there are still patient subgroups being in need of more aggressive treatment strategies including GPI. In practice, it might be reasonable to perform a baseline assessment of hemorrhagic risk facilitating the choice of an antithrombotic regimen with a favourable safety and efficacy profile. With this tailored therapy it might be possible to further improve outcomes for individual patients with ACS.
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PMID:Safety and efficacy of bivalirudin in acute coronary syndromes. 1847 66


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