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)

Quantitative (or semiquantitative) risk stratification is becoming a more accurate and feasible way to define both overall risk and likelihood of benefit from more potent and invasive therapies. LMWH appears to be at least as good, and likely modestly better than, unfractionated heparin, and when used for patients undergoing revascularization, it should be continued until revascularization. GP IIb/IIIa inhibitors are highly effective for coronary intervention, as well as for "up-front" use in high-risk ACS patients in an environment in which intervention is commonly used. In spite of the new guidelines, a clear delineation to the practitioner of which treatments are proven effective, in which patients, and in what combinations, remains challenging. Best estimates are that only 50% to 75% of ideal patients are currently receiving proven therapies. Better methods are needed to fully integrate proven effective treatments into practice.
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PMID:Acute coronary syndromes: introducing new therapies into established guidelines. 1143 52

The primary pathophysiologic mechanism underlying all non-ST-segment elevation acute coronary syndromes (NSTE ACS) is the formation of platelet-rich coronary thrombi in response to spontaneous or intervention-induced endothelial damage with exposure of subendothelial substrates. Antagonists of the glycoprotein (GP) IIb/IIIa receptor ameliorate this process by blocking the final common pathway for platelet aggregation. Based upon collective data in over 24,000 patients, clinical trials have demonstrated that treatment of NSTE ACS patients with GP IIb/IIIa agents results in an approximate 12% relative risk reduction in the incidence of death or myocardial infarction at 30 days. The magnitude of this clinical benefit is increased in patients who are troponin-positive and who are referred for early percutaneous intervention. Potential benefits of GP IIb/IIIa inhibitor use must be weighed against an increased risk of bleeding. Ongoing controversies exist concerning the relative efficacy of different GP IIb/IIIa antagonists, the accurate use of platelet function tests to define safe and efficacious drug dosing, the adjunctive use of additional anti-thrombotic agents, and the optimal timing of upstream therapy before diagnostic cardiac catheterization and revascularization.
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PMID:Small peptide GP IIb/IIIa receptor inhibitors as upstream therapy in non-ST-segment elevation acute coronary syndromes: results of the PURSUIT, PRISM, PRISM-PLUS, TACTICS, and PARAGON trials. 1170 7

Glycoprotein IIb/IIIa inhibitors have become the standard of care for patients undergoing percutaneous coronary intervention (PCI) and for those presenting with non-ST-segment elevation myocardial infarction (NSTE-ACS). Clinical effects of GP IIb/IIIa inhibitors in PCI and NSTE-ACS strongly correlate with potency, consistency, and durability of platelet aggregation inhibition. Under standardized conditions [light transmission aggregometry (LTA), 20 micromol adenosine diphosphate (ADP) as an agonist, and D-phenylalanyl-L-propyl-L-arginine chloromethyl ketone (PPACK) as an anticoagulant], we demand consistent platelet aggregation inhibition >80% during the time of PCI (initial balloon inflation), and during the entire duration of therapy in NSTE-ACS. The benefit of abciximab (bolus 0.25 mg/kg plus infusion 10 microg/kg/min) correlates with >80% inhibition of platelet aggregation during the intervention (PCI) and immediately thereafter (<6 hours). The absence of a benefit with abciximab in NSTE-ACS is most likely due to <80% inhibition during the major part of the infusion period (>6 hours). Tirofiban does not achieve >80% inhibition at the time of PCI at a dose of 10 microg/kg bolus plus 0.15 microg/kg/min infusion, and at a dose of 0.4 lg/kg/min loading infusion for 30 minutes plus 0.1 microg/kg/min maintenance infusion, the target value is only reached after 18 h. Eptifibatide (double-bolus 180 microg/kg 10 min apart, followed immediately by a 2.0 microg/kg/min infusion) provided an instant, consistent, and durable antiplatelet effect for the entire duration of infusion, and a significant clinical benefit in both PCI (non-ACS patients) and medically managed NSTE-ACS patients.
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PMID:Pharmacodynamic and clinical trials of glycoprotein IIb/IIIa inhibitors and potential relationship of results to dosing. 1265 67

Despite widespread use of stents and GP IIb/IIIa antagonists, complications following percutaneous treatment of thrombus-rich lesions continue to plague patients with ACS. In these patients the angiographically evident coronary thrombosis may represent a high degree of thrombus burden, which leads to a higher level of microembolization and its clinical sequelae. New catheter-based thrombus burden reduction systems and distal protection devices show promise for improving the prognosis of these high risk patients by decreasing distal microembolization, and thereby preventing myonecrosis. Careful procedural timing and patient selection are also likely to improve outcomes and resource utilization in the management of ACS patients.
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PMID:Coronary intervention in thrombus-rich lesions: beyond stents and glycoprotein IIb/IIIa inhibitors. 1465 Jan 5

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

Patients with CKD and CAD have traditionally been a difficult population to diagnose and treat in the setting of ACS. In addition to having poorer outcomes post-ACS, data are lacking regarding best treatments available. Aggressive interventional and medical treatments in this group with already poor outcomes are not necessarily contraindicated and should always be considered. The appalling outcome for CKD patients post-ACS is improved by many therapies shown to benefit in the non-CKD patients. Data suggest that troponins are useful markers in CKD patients, that major bleeding is not increased with the use of GP IIb-IIIa antagonists, that thrombolytics have been used successfully in CKD patients, and that PCI electively and as a primary treatment for ACS is successful and probably more beneficial to treatment.
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PMID:Treatment of acute coronary syndromes in patients who have chronic kidney disease. 1575 68

The patients presenting acute coronary syndrome with or without ST segment elevation form a heterogeneous population and thus the short and long-term risk of death or recurrent ischemic events can vary considerably. During ACS without ST elevation (unstable angina and non-ST elevation MI), the evaluation of risk is an essential step in the management of such patients, because it determines ulterior strategy. This evaluation is simple and reliable, and is principally based on three scores: the TIMI, the GRACE Score or the PURSUIT. Thanks to this stratification, high and medium-risk patients are able to benefit from early invasive management (stents and anti-GPIIb/IIIa) as recent studies have clearly shown. Even if immediate management of patients with non-ST elevation ACS does not take account of risk stratification, using such information in the medium and long-term does help determine the prognosis. Finally, the risk profile score, whatever the score used is today an essential tool, which helps qualify and especially compare patients included in international clinical studies.
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PMID:[Stratification scores for risk in the context of acute coronary syndromes]. 1610 13

In the last decade, acute coronary syndromes without ST elevation (ACS ST-) have become a clinical entity encompassing previous technologies such as acute coronary insufficiency and non-Q wave myocardial infarction. The recognition of its risks and, above all, the development and adaptation of medical and interventional strategies have transformed the prognosis. Patients presenting with ACS ST- are not all identical and do not all have the same prognosis; based on this observation, a number of prognostic scores have been proposed which help decide whether to use drugs such as GP IIb/IIIa inhibitors or coronary angioplasty. Conservative and aggressive strategies are opposing choices but risk stratification allows the treating physician to take a safe decision in the majority of cases. Besides angioplasty and GP IIb/IIIa inhibitors, the basic treatment (aspirin, low molecular weight heparin, clopidogrel, betablockers) should of course be prescribed and its efficacy has contributed to a better outcome in these patients. The recommendations of the scientific societies have evolved with time and increased understanding, allowing an evidence-based approach to the management of ACS ST- patients.
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PMID:[Acute coronary syndromes without ST elevation. State-of-the-art, recommendations, and best practices]. 1637 2

Background In patients with non-ST elevation acute coronary syndrome (NST-ACS) that is treated invasively, glycoprotein (GP) IIb/IIIa inhibitors can be used either as upstream treatment in a coronary care unit or as downstream provisional treatment in selected patients who are undergoing percutaneous coronary intervention (PCI). The relative advantage of either strategy is unknown. The purpose of this study was to assess 30-day outcome of patients enrolled in a prospective NST-ACS registry and treated invasively with either of these two therapeutic strategies. Methods Patients treated invasively (coronary arteriography within 4 days of admission), in the prospective registry ROSAI-2, were divided into two groups according to the upstream use of GPIIb/IIIa inhibitors (n = 241), or not (n = 548). In the latter group, 76 (14%) patients received GPIIb/IIIa in association with a PCI procedure. Clinical and angiographic characteristics as well as in-hospital and 30-day outcome of these two groups of patients were compared. Results The two groups were similar with respect to age, sex, presence of hypertension, diabetes, number of PCI procedures. However, patients treated with upstream GPllb/llla blockers had more frequently ST-segment depression (P = 0.002), a high TIMI risk score (P = 0.01) and were more frequently admitted to centres with Cath Lab facilities (P = 0.001). At 30-day follow-up, the composite of death, acute myocardial infarction and stroke, as well as major bleeding, was not significantly different between the two groups, although it occurred more frequently in patients who received upstream GPIIb/IIIa blockers (9.5% versus 5.7% and 1.7% versus 0.2%, respectively). By multivariate analysis, diabetes [odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.2-4.09] and a diagnosis on admission of non-Q-wave myocardial infarction (OR = 2.0, 95% Cl = 1.10-3.6) were independently related to outcome. No additional risk or benefit was related to upstream GPIIb/IIIa inhibitor treatment (OR = 1.5, 95% Cl = 0.84-2.68). Conclusions Among invasively-treated patients with NST-ACS, upstream treatment with GPIIb/IIIa inhibitors was used in those with a higher clinical risk profile, whereas downstream treatment was reserved for a limited number of patients undergoing PCI. Thirty-day outcome was similar in the two groups, irrespective of the treatment strategy used.
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PMID:Use of glycoprotein IIb/IIIa inhibitors in invasively-treated patients with non-ST elevation acute coronary syndrome. 1664 80

Since efficacy of small volume centers performing coronary and angioplasty is questioned, we present our data for 2003. In 2003, 669 coronary examinations were performed in our unit (average age 68 years, 67% men) with 215 angioplasties. We take charge essentially Acute Coronary Syndrome (99%), with 37% ACS ST +. The radical approach was taken in 15% of cases. We used anti GP IIb/IIIa in 67% of cases (only abciximab), the rate of stenting was 84% with 43.6% of Direct Stenting. The primary angiographic results were good in 98% of cases. The rate of Restenosis was 6%. The hospital mortality was 2.8%. So we think that coronary and angioplasty in a small volume center can be performed with safety and a level of success in accordance with the data of the literature.
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PMID:[Results of percutaneous coronary intervention in a hospital with a low case load]. 1718 26


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