Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute ischemic coronary syndromes of unstable angina and non-Q-wave myocardial infarction are most commonly caused by intracoronary thrombosis at the site of ruptured atherosclerotic plaque. The main goals of therapy are the relief of ischemia and prevention of life-threatening thrombotic events. Current antithrombotic management includes heparin and aspirin, but recent insights into the pathophysiology of these syndromes have revealed that more effective management may be achieved by direct inhibition of the final common pathway to platelet aggregation--the platelet glycoprotein (GP) IIb-IIIa receptor. Earlier studies of the reversible peptide inhibitor of the GP IIb-IIIa receptor, eptifibatide (INTEGRILIN), in patients with unstable angina have demonstrated its potential in reducing acute ischemic events. The Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, the largest clinical trial of any GP IIb-IIIa receptor inhibitor to date, is a recently completed phase III evaluation of eptifibatide as primary management for patients with acute coronary syndromes presenting without persistent ST-segment elevation.
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PMID:Design and methodology of the PURSUIT trial: evaluating eptifibatide for acute ischemic coronary syndromes. Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy. 929 Dec 44

Aspirin is accepted as standard therapy in the management of acute coronary syndromes, but has significant limitations, including intolerance, allergy, resistance, peptic ulceration, and intracranial hemorrhage. Recent trials involving approximately 18,000 patients with unstable angina have investigated the efficacy and safety of glycoprotein IIb/IIIa receptor antagonists, which block the final common pathway of platelet aggregation. The Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) trial compared tirofiban with heparin and found a 33% reduction in the composite end point of death, myocardial infarction, or refractory ischemia at 48 hours. In the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial, patients were randomly assigned to receive either heparin, tirofiban, or both. At 7 days, the patients who had received heparin and tirofiban had a 34% lower incidence of the composite end point of death, myocardial infarction, or refractory ischemia than those treated with heparin alone. The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial randomly assigned patients to receive either eptifibatide or placebo. At 30 days, the rate of death or myocardial infarction was reduced by 9.6% in the eptifibatide group compared with the placebo group. In the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON) trial, patients were randomly assigned to receive either low- or high-dose lamifiban with or without heparin, or heparin alone. There were no differences between the treatment groups at 30 days, but at 6 months the patients randomly assigned to receive low-dose lamifiban had a 23% lower incidence of death or myocardial infarction, perhaps because of long-term passivation of the plaque. Overall, IIb/IIIa antagonists have been shown to be safe and beneficial in patients with unstable angina, particularly during the infusion period. However, there remain a number of unanswered questions concerning treatment with these agents, such as the appropriate dosing regimens and the safety and efficacy of combining intravenous antiplatelet therapy with other agents such as low-molecular-weight heparin, thrombolytic agents, and oral agents.
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PMID:Newer antiplatelet agents in acute coronary syndromes. 1057 64

Thrombin activity has been implicated as a mechanism for failed reperfusion and reocclusion following thrombolysis. Aggregating platelets provide a phospholipid surface on which prothrombin is cleaved to form thrombin. We examined markers of thrombin generation and activity in patients enrolled in a randomized, placebo-controlled, dose escalating trial of the platelet glycoprotein IIb-IIIa inhibitor eptifibatide (Integrilintrade mark) administered concomitantly with tissue plasminogen activator for the treatment of myocardial infarction. Measurements were obtained at baseline, at 90 minutes, and at 6, 12, and 24 hours after starting therapy. Eptifibatide inhibited platelet aggregation in response to 20 microM ADP. Levels of fibrinopeptide A (FPA), thrombin-antithrombin complexes (TAT), and prothrombin fragment 1.2 (F1.2) were not lower in patients treated with eptifibatide than in the control group. In the course of dose escalation, two groups of patients received the same 135 microg/kg bolus of eptifibatide, one with and one without a heparin bolus. FPA levels were dramatically lower in the heparin-treated patients. Levels of FPA, TAT, and F1.2 were not higher in patients with than in those without recurrent ischemia, or in patients without than in those with Thrombolysis in Myocardial Infarction (TIMI) grade 3 angiographic flow at 90 minutes. These data suggest that thrombin generation and activity persist following thrombolysis, despite inhibition of platelet aggregation, and that treatment with inhibitors of thrombin activity may be required even when glycoprotein IIb-IIIa inhibitors are used.
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PMID:Inhibition of platelet aggregation with a glycoprotein IIb-IIIa antagonist does not prevent thrombin generation in patients undergoing thrombolysis for acute myocardial infarction. 1059 Jan 83

Computer-assisted continuous monitoring of the ST-segment allows detection and quantification of recurrent ischemia in patients with acute coronary syndromes. In a substudy of the PURSUIT (Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy) trial, this technique was used to evaluate the effects of the glycoprotein IIb/IIIa inhibitor eptifibatide on the incidence and severity of recurrent ischemia, and to investigate the relationship between recurrent ischemia and the occurrence of subsequent death or myocardial (re)infarction. A total of 258 patients with unstable angina or evolving myocardial infarction without ST elevation were monitored for 24 hours during infusion with either eptifibatide or placebo with a computer-assisted 12-lead ECG-ischemia monitoring device. Recurrent ischemic episodes were identified by an automated computer algorithm. Two hundred and sixteen patients (84%) had ECG recordings suitable for analysis. Ischemic episodes were detected in 35 (33%) of the 105 eptifibatide patients and in 32 (29%) of the 111 placebo patients (not significant). No difference in ischemic burden was apparent between both treatment groups. Patients who exhibited 2 or more episodes of recurrent ischemia more frequently died or suffered a myocardial infarction, both at 7 and 30 days, as well as through the 6-month follow-up. A greater ischemic burden was significantly related to adverse outcome during the 6-month follow-up period. Real-time computer-assisted continuous multilead ECG-ischemia monitoring may help to identify patients with unstable coronary syndromes at increased risk of adverse outcome and, thus, allow for better prognostic triage and more appropriate selection of therapeutic strategies. Integration of these systems in coronary care units and emergency wards should, therefore, be recommended.
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PMID:Recurrent ischemia during continuous 12-lead ECG-ischemia monitoring in patients with acute coronary syndromes treated with eptifibatide: relation with death and myocardial infarction. PURSUIT ECG-Ischemia Monitoring Substudy Investigators. Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy. 1081 6

Clinical experience suggests that patients treated with the glycoprotein (GP) IIb/IIIa inhibitor abciximab (ReoPro , Eli Lilly and Company, Indianapolis, Indiana) may be at increased risk of thrombocytopenia. This case report details the successful use of the GP IIb/IIIa inhibitor eptifibatide (Integrilin , COR Therapeutics, South San Francisco, California) in a patient who developed acute thrombocytopenia (platelet count: 67,000/mm3) approximately 10 hours after initiation of abciximab therapy. Five hours after abciximab was discontinued, platelet count returned to normal (191,000/mm3) and eptifibatide was started because of persistent electrocardiographic evidence of ischemia. The patient underwent diagnostic catheterization during eptifibatide therapy, which was administered for approximately three days. Four days after the initial course of therapy with eptifibatide was discontinued, percutaneous revascularization with adjunct eptifibatide was performed. During both courses of eptifibatide therapy, platelet counts remained in the normal range (> 100,000/mm3) and no adverse ischemic or bleeding events occurred.
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PMID:Platelet receptor glycoprotein IIb/IIIa inhibition with eptifibatide in a patient with thrombocytopenia after treatment with abciximab. 1102 16

The optimal management approach for patients with non-ST-segment elevation acute coronary syndromes continues to be an issue of debate. An ischemia-guided strategy appears to be effective as an alternative to either a very conservative "wait-and-see" approach or a very aggressive routine revascularization approach. The need for another approach is supported by the lack of conclusive evidence-based results favoring an early routine invasive treatment strategy. In the Thrombolysis in Myocardial Infarction (TIMI) IIIB trial, there were no differences in the incidence of death or myocardial infarction (MI) between patients treated with an early invasive approach and those treated with a conservative approach to treatment. Significantly worse outcomes were shown in patients assigned to an early invasive strategy in the Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) trial at 1-year follow-up (111 clinical events in the invasive group vs 85 in the conservative group; p = 0.05). Registry information, including that from the Organization to Assess Strategies for Ischemic Syndromes (OASIS), which included approximately 8,000 patients with unstable angina or suspected MI, has even suggested an excess hazard with a routine invasive approach. Patients with non-ST-segment elevation MI observed in the Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO)-IIB and Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trials also fared better with an ischemia-guided strategy. Even the recent FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC II) trial investigators had to be very selective relative to eliminating high-risk patients in the first week and treating with intense anti-ischemic therapy and 5-7 days of low-molecular-weight heparin therapy to show an advantage for assigned revascularization. A careful clinical evaluation with attention to early risk stratification is essential in the ischemia-guided approach. The Braunwald classification for unstable angina helps identify independent clinical predictors of a poor outcome; high risk is clearly associated with Braunwald class III and type C. Electrocardiographic and biochemical markers for myocardial necrosis (cardiac troponin T or I) are important tools for assessing the presence and degree of ischemia and associated risk for adverse outcome. Noninvasive evaluation of left ventricular ejection fraction is essential for identifying those at high risk due to impaired contractile function. When these conventional markers do not provide conclusive information, noninvasive stress testing is most helpful to further identify those at highest risk for revascularization.
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PMID:An ischemia-guided approach for risk stratification in patients with acute coronary syndromes. 1120 16

Background- A reactivation of ischemia after the discontinuation of intravenous heparin in acute coronary syndromes has been described. The effect of glycoprotein IIb/IIIa blockade on heparin rebound is unknown. Methods and Results- Patients with acute coronary syndromes who received heparin therapy but not initial revascularization in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial were analyzed. Rates of death or myocardial (re)infarction while on heparin therapy and in 12-hour periods in the 2 days after heparin discontinuation were compared between eptifibatide and placebo. There was no difference between study groups in event rates during heparin infusion. In the 12 hours after heparin discontinuation, there was a 2.5-fold increase in all events, an 8-fold increase in death, and a 2-fold increase in myocardial infarction. However, in the 12 hours after heparin discontinuation, there was a significantly lower rate of events (1.68% versus 2.53%, P=0.03) and death (0.77% versus 0.21%, P=0.002) in the eptifibatide group compared with the placebo group. When only considering patients who were on study drug at the time of heparin discontinuation, the reduction in the combined end point was marginally significant, but the difference in the rate of death remained significant (0.68% versus 0.06%, P=0.004). In logistic regression analyses, the multivariate predictors of rebound events were the duration of heparin therapy, age, North American site, and lack of eptifibatide treatment. Conclusions- An increase in death or myocardial infarction occurs in the 12 hours after heparin discontinuation in patients with acute coronary syndromes. This rebound is attenuated by glycoprotein IIb/IIIa inhibition with eptifibatide.
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PMID:Attenuation of rebound ischemia after discontinuation of heparin therapy by glycoprotein IIb/IIIa inhibition with eptifibatide in patients with acute coronary syndromes: observations from the platelet IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial. 1173 93

The benefits of glycoprotein (GP) IIb-IIIa inhibitors in percutaneous coronary intervention are well established, but the experience with these agents in the setting of peripheral interventions is limited. In this single-center pilot trial, the safety and feasibility of adjunctive treatment with the GP IIb-IIIa inhibitor eptifibatide (INTEGRILIN, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, and Schering-Plough Corporation, Kenilworth, New Jersey) was evaluated in 85 patients undergoing percutaneous transluminal angioplasty or stenting for severe claudication or critical limb ischemia. Eptifibatide treatment was safe, with low rates of major bleeding (3.5%) and thrombocytopenia (1.2%); one patient developed a post-procedure compartment syndrome requiring fasciotomy. The procedure was technically successful (defined as <30% residual stenosis or >50% increase in vessel diameter) in 84 of 85 (98.8%) patients. None of the patients required target vessel revascularization (TVR) during hospitalization, and only 1 patient (1.2%) required TVR within 30 days. These results demonstrate that adjunctive use of eptifibatide during percutaneous peripheral intervention is safe and supports further studies to establish the potential efficacy of GP IIb-IIIa inhibitors in this setting.
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PMID:Glycoprotein IIb-IIIa receptor inhibition with eptifibatide in percutaneous intervention for symptomatic peripheral vascular disease: the circulate pilot trial. 1628 82

Anemia has been associated with adverse outcomes in patients with acute coronary syndromes (ACS). However, the underlying pathophysiologic mechanisms have not been well elucidated. We sought to determine the independent relation between the hemoglobin level and recurrent ischemia in patients with non-ST-segment elevation ACS using continuous electrocardiographic monitoring. In the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) trial, 746 patients presenting with non-ST-segment elevation ACS underwent continuous ST-segment monitoring for 48 hours. The data were analyzed independently at a core laboratory. We stratified the study population according to their hemoglobin level on presentation. The primary outcome of the study was recurrent ischemia, defined as ST-segment shifts on continuous electrocardiographic monitoring. Of the 705 patients with analyzable data, 64 had a baseline hemoglobin level <120 g/L, 259 had a level of 120 to 139 g/L, 315 had a level of 140 to 159 g/L, and 67 had a level >160 g/L. The corresponding rates of recurrent ischemia were 39.1%, 22.0%, 15.6%, and 11.9% (p for trend <0.001). A lower hemoglobin level was associated with advanced age, co-morbidities, and a higher GRACE risk score. In multivariable analysis adjusting for these confounders, lower hemoglobin levels retained a significant independent association with recurrent ischemia (p for trend = 0.004). In conclusion, a lower hemoglobin level at presentation was independently associated with recurrent ischemia detected by continuous electrocardiographic monitoring in the setting of non-ST-segment elevation ACS. This suggests that anemia might predispose patients to recurrent ischemia, which could be an important underlying mediator of worse outcomes in patients with lower hemoglobin levels.
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PMID:Relation between hemoglobin level and recurrent myocardial ischemia in acute coronary syndromes detected by continuous electrocardiographic monitoring. 2141 90