Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The principal new clinical approaches to the treatment of acute coronary thrombosis are reviewed. They include fibrinogen platelet receptor antagonists (anti GP IIb-IIIa) and direct thrombin inhibitors. The anti GP IIb-IIIa have been shown to be effective in unstable angina and in the prevention of acute coronary occlusion after transluminal angioplasty. Thrombin inhibitors, the leader being hirudine, also give promising results. The real clinical benefits of these agents and the risk of haemorrhage that they incur in monotherapy or in association, will only become clear when the results of large scale trials which are under way at present, become available. Other antiplatelet agents (clopidogrel, thromboxane inhibitors) are also discussed.
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PMID:[New therapeutic prospects in acute coronary thrombosis]. 764 55

Patients with unstable angina, refractory to intensive medical therapy, are at high risk for developing thrombotic complications, such as recurrent ischemia, myocardial infarction and coronary occlusion during coronary angioplasty. As both platelet aggregation and/or thrombus formation play an important role in this ongoing ischemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) or thrombolytic therapy (alteplase) might be able to modify the clinical course and underlying coronary lesion morphology. To evaluate whether alteplase or c7E3 could influence the incidence of complications, we randomized 36 and 60 patients, respectively to alteplase or placebo, or c7E3 or placebo. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite maximal tolerated medical therapy. Patients were randomized in both studies after initial angiography had demonstrated a culprit lesion amenable for angioplasty. After study drug infusion quantitative angiography was repeated and angioplasty performed. Recurrent ischemia during study drug infusion occurred in 5, 6, 9 and 16 patients from the alteplase, placebo, c7E3 and placebo group, respectively. Major events defined as death, myocardial infarction or urgent intervention occurred in 7, 3, 1 and 7 patients, respectively. Two patients died: one in the alteplase group and one in the placebo group from the c7E3 study. The first patient due to retroperitoneal hemorrhage, the second as a result of recurrent infarction. Qualitative angiography showed resolution of clots in the c7E3 group only, while the same group of patients showed in 20% an improvement in TIMI flow grade, without deterioration in any patient from this group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between clinical course and quantitative analysis of the ischemia related artery in patients with unstable angina pectoris, refractory to medical treatment. Results of two randomized trials. The European Cooperative Study Group. 787 57

Patients with unstable angina, refractory to intensive medical therapy, are at high risk of developing thrombotic complications, such as myocardial infarction and coronary occlusion during coronary angioplasty. As platelet aggregation and thrombus formation play an important role in this ongoing ischaemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) has been designed to modify the clinical course and underlying coronary lesion morphology. To evaluate whether c7E3 could influence the incidence of complications, we randomized 60 patients to c7E3 or placebo after initial angiography had demonstrated a culprit lesion amenable for angioplasty. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite intensive medical therapy. After study drug bolus and infusion, angiography was repeated and angioplasty performed. Recurrent ischaemia during study drug infusion occurred in nine and 16 patients from the c7E3 and placebo groups, respectively (P = 0.06). Major events defined as death, myocardial infarction or urgent intervention occurred in one and seven patients, respectively (P = 0.03). One patient from the placebo group died as a result of recurrent infarction. Resolution of clots was only observed in the c7E3 group, combined with improvement in TIMI flow grade in 20% of patients. Quantitative angiography showed an improvement in percentage diameter stenosis in the c7E3 group, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. No excess bleeding was observed in the treatment group. Thus, c7E3 bolus and infusion, combined with heparin and aspirin improved the clinical course, the coronary lesion morphology and rheology in patients with unstable angina, refractory to medical treatment.
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PMID:Antiplatelet therapy in therapy-resistant unstable angina. A pilot study with REO PRO (c7E3). 886 17

The optimal treatment of acute thrombotic complications in the Catheterization Laboratory has not been defined yet, due to the limited efficacy shown by various pharmacological regimens, even when associated to coronary angioplasty (PTCA). The aim of our study was therefore to evaluate the effects of abciximab (ReoPro), a new potent inhibitor of the platelet glycoprotein IIb/IIIa, when administered as a "rescue" treatment for acute thrombotic coronary occlusion during diagnostic or interventional procedures. Sixteen patients (12 males, 4 females, mean age 59.3 +/- 9.2 years, range 43-77 years), with unstable angina and consecutively treated with abciximab due to clinical instability attributable to coronary thrombosis angiographically proven during PTCA (9 cases) or diagnostic angiography (7 cases), were identified. The individual angiographic films and medical records were then reviewed in order to evaluate the effects of treatment on coronary flow, thrombus size and occurrence of in-hospital adverse events: death, non-fatal acute myocardial infarction (AMI), need for urgent myocardial revascularization and hemorrhage. The administration of abciximab, in association with PTCA (associated in turn with stent implantation in 8 cases), induced a significant increase of coronary TIMI flow grade (0.3 +/- 0.6 vs 2.4 +/- 0.9; p < 0.05) and a significant decrease of thrombus "score" (size) 2.4 +/- 0.9 vs 1.3 +/- 0.6; p < 0.01). No deaths nor need for urgent myocardial revascularization were observed; in 31% of cases (5 patients) evolution towards AMI occurred, while however 94% of cases (15 patients) had a coronary occlusion before treatment. No major hemorrhagic complications were observed, while in 12% of cases (2 patients) a groin hematoma associated with moderate hemoglobin drop, developed. In conclusion, the administration of abciximab, associated with the common "rescue" interventional procedures, in patients with acute thrombotic coronary occlusion in the Catheterization Laboratory, appears to be effective in restoring adequate coronary flow and reducing the thrombus size (limiting therefore the evolution towards AMI), and safe, not having been associated with significant hemorrhagic complications.
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PMID:[Initial experience with the use of abciximab in the salvage treatment of acute coronary thrombosis in the Hemodynamics Laboratory]. 992 89

The immediate results of transluminal coronary angioplasty (TCA) have improved considerably during recent years. Balloon dilatation of the arterial stenosis is the basis of this technique of revascularisation but new tools may be used to treat specific lesions. Coronary occlusion is the most feared complication of TCA. It may cause myocardial infarction or death of the patient. It is usually secondary to dissection and/or thrombus of the artery. The implantation of a stent successfully treats most cases of dissection. New anti-platelet (GP IIb/IIIa) drugs seem to be very effective in the prevention and treatment of the thrombosis. The systematic use of ticlopidine limits the risk of stent occlusion. Improved features enable satisfactory implantation of stents in the majority of cases. In some patients, the clinical consequences of occlusion may be limited by vascular bypass techniques, especially intra-aortic balloon pumping. In other cases, emergency coronary bypass surgery may be necessary. When TCA is considered to be a very high risk procedure, effective surgical cover is essential.
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PMID:[Acute complications of coronary angioplasty: prevention and management]. 1059 37

Reperfusion injury after coronary occlusion is in part mediated by leukocyte activation and adhesion. Platelets may interact with polymorphonuclear granulocytes (PMNs), causing aggravated reperfusion injury. We studied whether c7E3Fab, a chimeric Fab fragment blocking platelet glycoprotein (GP) IIb/IIIa, decreases PMN-platelet-dependent myocardial dysfunction after ischemia. Isolated guinea pig hearts (n=5 per group) perfused at a constant flow of 5 mL/min were subjected to ischemia (15 minutes, 37 degrees C) and reperfusion. Human PMNs (10x10(6) cells, 3 mL), platelets (400x10(6), 3 mL), and fibrinogen (1 mg/mL) were infused for 3 minutes after 2 minutes of reperfusion, with or without c7E3Fab. Flow cytometry detected GPIIb/IIIa (platelets) and MAC-1 (aMbeta2, PMNs) as well as coaggregates of both in the effluent, whereas double-fluorescence microscopy visualized intracoronary PMN-platelet coaggregates. Postischemic recovery of pressure-volume work (12-cm H(2)O preload and 60-mm Hg afterload) was defined as the ratio of postischemic to preischemic external heart work (mean+/-SEM). c7E3Fab reduced platelet GPIIb/IIIa detection to 10% of controls, blocked a transcoronary MAC-1 increase (+25% without versus -23% with c7E3Fab), and inhibited PMN-platelet coaggregation in the effluent (49+/-12% without versus 17+/-2% with c7E3Fab) as well as in the hearts themselves (5.0+/-0.7/cm(2) without versus 1.2+/-0.3/cm(2) surface area with c7E3Fab). Postischemic recovery of external heart work (83+/-5% in cell-free hearts) declined to 46+/-4% after postischemic PMN-platelet infusion, but not in the presence of c7E3Fab (74+/-11%) or LPM19c (71+/-6%). We conclude that c7E3Fab inhibits formation of PMN-platelet aggregates during myocardial reperfusion, an effect that protects against PMN-platelet-dependent stunning.
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PMID:c7E3Fab reduces postischemic leukocyte-thrombocyte interaction mediated by fibrinogen. Implications for myocardial reperfusion injury. 1103 Dec 8

Both anticoagulants and antiplatelet agents have been advocated, used and studied for the treatment of acute ischemic stroke. Randomized trials of unfractionated heparin, low-molecular-weight heparin and heparinoids have failed to show an overall benefit to these agents largely because the benefits in reducing thromboembolic events are offset by the increased risk of bleeding complications. The International Stroke Trial, the Trial of ORG 10172 Acute Stroke Treatment and studies of fraxaripine all failed to show an overall benefit to anticoagulation in the patients studied. Aspirin has been shown to offer a modest benefit when studied in patients treated within 48 h of stroke onset. Ancrod is an antithrombotic agent that acts by reducing circulating fibrinogen levels. Patients treated within 3 h of stroke symptom onset had a better functional outcome at 90 days compared to placebo-treated patients with both the benefits and the risk of intracerebral bleeding related to the fibrinogen lowering achieved. Abciximab is a blocker of the platelet GPIIb/IIIa receptor. A dose finding safety study suggests that in doses up to that typically given in patients with acute coronary occlusion syndromes, there is no increased risk of symptomatic intracerebral bleeding and suggestions of potential benefits on neurological outcome.
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PMID:Antithrombotic therapy in the acute phase: new approaches. 1124

This guideline describes the recognition and management of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI). These are two of the three components of the acute coronary syndrome (ACS). These forms of ACS most often arise from erosion or rupture of coronary atherosclerotic plaque and subsequent thrombus formation causing incomplete coronary occlusion. The term ACS, as used in this guideline, refers to these two components only. The third component, not discussed here, is ST-segment elevation myocardial infarction (STEMI), which is most frequently associated with complete coronary occlusion. ACS is a clinical emergency requiring urgent assessment. It is characterised by chest pain, ST-segment changes in the electrocardiogram (ECG) and a rise in the serum markers of myocardial injury/infarction. ACS encompasses a variety of clinical presentations. Risk stratification is essential to enable triage of patients to the optimal level of care and specific therapy. Careful clinical assessment is the cornerstone of this risk stratification. The pharmaceutical treatment of ACS is directed primarily at the dissolution of the developing intracoronary thrombus by antiplatelet (aspirin and clopidogrel) and anticoagulant therapy (heparin), and secondarily to the relief of symptoms by anti-anginal and analgesic medications. Low-molecular-weight heparin (LMWH) is at least as effective and safe as standard intravenous unfractionated heparin (UH). Coronary angiography is advised for all high-risk patients and those in whom reversible ischaemia or left ventricular dysfunction is discovered. The need for coronary revascularisation is dictated by the findings at angiography. In high-risk patients, appropriate, early revascularisation is recommended in preference to standard medical therapy and 'ischaemia-driven' revascularisation. The glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors should be used in association with percutaneous coronary intervention (PCI) in high-risk patients. All patients with ACS should receive secondary preventive treatment. It is imperative that they stop smoking. Dietary modification, physical rehabilitation, long-term low-dose aspirin use, b-blockade for those diagnosed with myocardial infarction, tight control of blood pressure, cholesterol lowering with a statin, and treatment with an angiotensin-converting enzyme (ACE) inhibitor should be prescribed.
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PMID:Management of acute coronary syndromes clinical guideline. 1243 90

BACKGROUND: Although balloon angioplasty has assumed an important role in the management of refractory unstable angina (UA), that is, UA that does not respond to conventional therapy, it is limited by complications related to thrombosis and acute coronary occlusion. The complication rate is higher in patients with UA than in those whose condition is stable. Preprocedural use of abciximab, a monoclonal platelet glycoprotein IIb/IIIa receptor blocker, has been used effectively in patients with UA, but its acceptance may be limited by safety concerns and economic constraints. The current trial investigated a protocol for abciximab pretreatment in patients with UA awaiting transfer from referring hospitals to a site of intervention (the 'drip and ship' protocol). AIMS: This observational study was conducted to evaluate whether a prophylactic, preprocedural regimen of abciximab can be safely and effectively administered to UA patients in referring hospitals while awaiting coronary angioplasty at the interventional clinic. METHODS: From April 1996 to December 1998, 168 consecutive patients with refractory UA (Braunwald class II or III) received abciximab prospectively at the referring clinic before undergoing PTCA or stent implantation at the interventional clinic. The following cost-conscious protocol was used: a 0.25 mg/kg bolus of abciximab followed by 10 micro g/min intravenously for 16 hours, in addition to intravenous nitrates, heparin and aspirin therapy. Patients were then transferred to a facility with PTCA capability via high-speed ambulance transport. No specific alterations of routine-transfer protocol were needed. Platelet aggregation studies were conducted during abciximab infusion. All interventions were performed while abciximab was given. Procedural and clinical success and long-term outcomes also were assessed. RESULTS: The primary angiographic success rate (patients with post-PTCA diameter stenosis < 50%) was 98%, and the in-hospital clinical success rate (angiographic success without major complications) was 98%. No major bleeding complications occurred during the abciximab pretreatment period. Platelet aggregation findings in the study patients showed a stable inhibition of >80% at the time of angioplasty. At 30-day follow-up, all patients were alive and 91% were free of major adverse events. Outcomes of balloon angioplasty and stenting were equally favorable, indicating no device-specific effect. Event-free survival at six months was 89% with a target vessel revascularization rate of 10%. CONCLUSION: Abciximab was administered safely and effectively to angioplasty patients with refractory UA awaiting transfer from a noninterventional setting to the site of angioplasty. These results extend the current knowledge base that has been established in randomized trials performed in interventional centers. The study protocol potentially could make abciximab therapy more feasible economically, and therefore more widely available to patients who are most likely to benefit from prophylactic administration.
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PMID:Safety and efficacy of treatment with platelet GPIIb/IIIa receptor blockade in unstable angina patients awaiting PTCA at a referring clinic. 1262 72