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)

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

Management and prognosis of acute coronary syndromes may be influenced by the availability of catheterization facilities at admitting hospitals. Treatment effects of tirofiban were examined in a Canadian cohort of 834 patients enrolled in the Canadian Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial according to admission into hospitals without (n = 322) or with catheterization facilities (n = 512). Hospital transfers for cardiac catheterization were facilitated using preexisting networks accelerated for the purposes of the protocol. In hospitals without facilities, the relative risks for occurrence of death, infarction, or refractory ischemia among patients receiving tirofiban plus heparin compared with heparin alone were 0.52 at 7 days (p = 0.02), 0.59 at 30 days (p = 0.03), and 0.70 at 180 days (p = 0.09); and for death or infarction, 0.32 (p = 0.02), 0.46 (p = 0.04,) and 0.51 (p = 0.03), respectively. Benefit was seen regardless of transfer status, with no statistically significant interaction between treatment, hospital type, and catheterization for any end point at any time point. The incidence of Thrombolysis In Infarction defined major bleeding with respect to therapy was not significantly different between hospital types. Thus, upstream treatment with tirofiban plus heparin confers clinical benefits in unstable angina and/or non-ST-segment elevation infarction patients regardless of whether initial presentation is to a hospital without catheterization facilities or to a hospital with such facilities.
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PMID:Upstream use of tirofiban in patients admitted for an acute coronary syndrome in hospitals with or without facilities for invasive management. PRISM-PLUS Investigators. 1117 17

Clinical outcomes of patients with unstable angina are variable. We sought to identify predictors of adverse clinical outcomes in patients with unstable angina and to investigate whether these factors would predict the magnitude of benefit achieved with platelet glycoprotein IIb/IIIa inhibition. We analyzed 20 variables in the 1,915 patients enrolled in the Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial. Five independent predictors were identified: age >65 years, prior coronary artery bypass grafting, antecedent aspirin use, antecedent beta-blocker use, and ST depressions on the presenting electrocardiogram. A risk score system was created using these predictors in which patients were assigned 1 point for the presence of each risk factor. There was a progressive increase in the rate of the composite end point of death, myocardial infarction, or refractory ischemia at 7 days with an increasing number of risk factors. For patients treated with heparin alone, the composite end point event rate was 6.5% in the group with 0 or 1 predictor, 14.6% in the group with 2 predictors, 22.7% in the group with 3 predictors, and 37.1% in the group with 4 or 5 predictors (p <0.00001). When dividing patients into low- (0 or 1 point), medium- (2 or 3 points), and high-risk (4 or 5 points) groups, the addition of tirofiban to heparin therapy was associated with no significant benefit in the low-risk group, a 5.2% absolute reduction in the medium-risk group (p = 0.05), and a 16% absolute reduction in the high-risk group (p = 0.0055). Thus, we have developed a risk score system using 5 variables that can be used to identify patients at high risk for death and cardiac ischemic events and who experience the greatest benefit from the addition of a glycoprotein IIb/IIIa inhibitor to their treatment regimen.
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PMID:A risk score system for predicting adverse outcomes and magnitude of benefit with glycoprotein IIb/IIIa inhibitor therapy in patients with unstable angina pectoris. 1152 55

The role of glycoprotein IIb/IIIa platelet receptor antagonist therapy for patients with an acute coronary syndrome (ACS) and a history of coronary artery bypass grafting (CABG) remains incompletely defined. We examined the outcomes of patients with an ACS and prior CABG who were treated with tirofiban versus placebo among subjects with prior CABG in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial. Of 1,570 patients treated with tirofiban plus heparin (n = 773) or heparin alone (n = 797), 231 had prior CABG. Compared with patients without prior CABG, those with prior CABG were more likely to have risk factors for a complicated ACS course, including severe coronary artery disease and heart failure (all p <0.0001), typically had clinical predictors of benefit from tirofiban, such as ST-segment depression (p = 0.01) or a TIMI risk score >or=4 (p <0.001), and were more likely to die or have a myocardial infarction or refractory ischemia at all time points examined (p <0.0001). Among patients with prior CABG, decreases in the incidence of death, myocardial infarction, or refractory ischemia with tirofiban and heparin versus heparin alone were noted at 7 and 30 days (7 days: 16.9% vs 29.0%, p = 0.035; 30 days: 25.0% vs 40.2%, p = 0.015). Trends toward a decrease in death, myocardial infarction, and refractory ischemia with tirofiban and heparin versus heparin alone in the prior CABG subgroup were noted at 48 hours and 180 days (48 hours: 6.5% vs 14.0%, p = 0.09; 180 days: 37.1% vs 48.6%, p = 0.057). Bleeding rates were similar in patients with and without prior CABG. Tirofiban was well tolerated and tended to decrease the considerable risk for ischemic ACS complications in patients with prior CABG.
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PMID:Tirofiban therapy for patients with acute coronary syndromes and prior coronary artery bypass grafting in the PRISM-PLUS trial. 1505 Apr 86

Although the efficacy of glycoprotein IIb/IIIa inhibition in non-ST-elevation acute coronary syndromes is greatest in patients who undergo percutaneous coronary intervention (PCI), it was hypothesized that high-risk patients managed without PCI also benefit. The TIMI risk score was calculated for 1,570 patients randomized to tirofiban plus heparin versus heparin in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial. In high-risk patients (score > or =4) treated without PCI, tirofiban reduced the risk for death, myocardial infarction, and refractory ischemia at 30 days (28.8% vs 21.9%; odds ratio [OR] 0.69, p = 0.04). This benefit was similar in magnitude as that for patients who underwent PCI (32.4% vs 22.2%; OR 0.60, p = 0.06). No benefit was evident in low-risk patients.
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PMID:Usefulness of tirofiban among patients treated without percutaneous coronary intervention (TIMI high risk patients in PRISM-PLUS). 1537 86