Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The platelet glycoprotein (GP) IIb/IIIa receptor can bind fibrinogen, von Willebrand factor, and other adhesive ligands; this binding is the final common pathway mediating platelet aggregation. The purpose of this study was to evaluate the safety and platelet inhibitory characteristics of the Fab fragment of the murine monoclonal anti-GPII/IIIa 7E3 antibody (m7E3 Fab) when administered intravenously as a single bolus dose, as a single and repeat bolus dose, and as a single bolus dose followed by continuous infusions of varying duration. Various dosage regimens of m7E3 Fab were studied in 74 patients with stable angina. Dosage regimens included single doses of m7E3 Fab from 0.1 to 0.3 mg/kg, a single dose of 0.20-0.30 mg/kg, and a repeat dose of 0.05 mg/kg, or a loading dose followed by a continuous infusion of m7E3 Fab for up to 36 hours. To assess the effect of m7E3 Fab on platelet function, quantitative blockade of GPIIb/IIIa receptors, inhibition of ex vivo platelet aggregation, and template bleeding time were measured in all patients. Dose-dependent inhibition of platelet function was evident in response to escalating bolus doses of m7E3 Fab, with maximum inhibition observed at 0.25-0.30 mg/kg body weight; at the 0.30 mg/kg dose, mean (+/- SE) GPIIb/IIIa receptor blockade was 81 +/- 3%, ex vivo platelet aggregation in response to 20 microM ADP was 14 +/- 6% of baseline, and the median bleeding time was > 20 minutes. Although platelet function gradually recovered following a single bolus injection, platelet inhibition could be sustained by continuous, low-dose infusion of the antibody. Platelet inhibition occurred within minutes, but m7E3 Fab that did not bind to platelets cleared rapidly from circulation. Sixteen percent of the m7E3 Fab-injected subjects exhibited low titer, human anti-murine antibody responses. No significant bleeding or allergic reactions were observed in any patients. One of the 74 patients developed transient thrombocytopenia soon after receiving m7E3 Fab. These studies establish that m7E3 Fab can be administered safely at doses that cause profound inhibition of platelet function.
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PMID:Blockade of the human platelet GPIIb/IIIa receptor by a murine monoclonal antibody Fab fragment (7E3): potent dose-dependent inhibition of platelet function. 857 49

The era of platelet glycoprotein (GP) IIb/IIIa receptor inhibition in cardiology was inaugurated in 1994 with the publication of the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) trial results. EPIC demonstrated that the GP IIb/IIIa blocker abciximab, administered as a bolus and 12-hour infusion, afforded protection against ischemic complications in high-risk patients undergoing angioplasty and atherectomy, including those with unstable angina or evolving myocardial infarction (MI). A significant reduction in the incidence of death, acute MI, or revascularization was apparent at 30 days and also sustained at 6-month and 3-year follow-up. The subsequent Evaluation in PTCA to Improve Long-Term Outcome with Abciximab GP IIb/IIIa Blockade (EPILOG) study extended these findings to the full spectrum of coronary intervention patients, confirming that abciximab provided similar benefits in low-risk patients as well. The EPILOG trial also proved that any excess bleeding risk associated with potent antiplatelet therapy could be brought down to placebo levels through the use of a low-dose, weight-adjusted heparin regimen, early vascular sheath removal, and elimination of routine postprocedural heparinization. The potential for an advantage of GP IIb/IIIa blockade in patients with refractory unstable angina/non-Q-wave MI was demonstrated in the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) trial, which showed that a 24-hour preprocedural abciximab infusion effectively stabilized these patients, thereby enhancing the safety of intervention and reducing the 30-day incidence of ischemic events. A similar pattern of benefit has emerged from clinical trials of such other GP IIb/IIIa inhibitors as eptifibatide, lamifiban, and tirofiban. Trials are currently underway to clarify the benefits of GP IIb/IIIa blockers in patients undergoing stenting and as an adjunct to thrombolytic therapy or primary angioplasty in patients with acute MI (ST-segment elevation).
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PMID:An overview of the results of clinical trials with glycoprotein IIb/IIIa inhibitors. 953 95

The era of platelet glycoprotein (GP) IIb/IIIa receptor inhibition in cardiology was inaugurated in 1994 with the publication of the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) trial results. EPIC demonstrated that the GP IIb/IIIa blocker abciximab, administered as a bolus and 12-hour infusion, afforded protection against ischemic complications in high-risk patients undergoing angioplasty and atherectomy, including those with unstable angina or evolving myocardial infarction (MI). A significant reduction in the incidence of death, acute MI, or revascularization was apparent at 30 days and also sustained at 6-month and 3-year follow-up. The subsequent Evaluation in PTCA to Improve Long-Term Outcome with Abciximab GP IIb/IIIa Blockade (EPILOG) study extended these findings to the full spectrum of coronary intervention patients, confirming that abciximab provided similar benefits in low-risk patients as well. The EPILOG trial also proved that any excess bleeding risk associated with potent antiplatelet therapy could be brought down to placebo levels through the use of a low-dose, weight-adjusted heparin regimen, early vascular sheath removal, and elimination of routine postprocedural heparinization. The potential for an advantage of GP IIb/IIIa blockade in patients with refractory unstable angina/non-Q-wave MI was demonstrated in the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) trial, which showed that a 24-hour preprocedural abciximab infusion effectively stabilized these patients, thereby enhancing the safety of intervention and reducing the 30-day incidence of ischemic events. A similar pattern of benefit has emerged from clinical trials of such other GP IIb/IIIa inhibitors as eptifibatide, lamifiban, and tirofiban. Trials are currently underway to clarify the benefits of GP IIb/IIIa blockers in patients undergoing stenting and as an adjunct to thrombolytic therapy or primary angioplasty in patients with acute MI (ST-segment elevation).
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PMID:An overview of the results of clinical trials with glycoprotein IIb/IIIa inhibitors. 959 18

Platelet membrane glycoproteins play a crucial role in ischemic complications after coronary stenting. Glycoprotein IIb-IIIa blockade reduces adverse clinical events after angioplasty but is associated with rare but profound thrombocytopenia that might increase hemorrhagic complications. Changes in platelet membrane glycoproteins of patients with angina who underwent coronary stenting and were treated with the GPIIb-IIIa antagonist abciximab (n=20) or with heparin (n=23) were studied. GPIb-IIIa receptor blockade and membrane glycoproteins were evaluated with immunological markers in venous blood samples taken before. 10, 24, 48, 72, and 96 h after initial treatment with either abciximab or heparin. Patients receiving abciximab therapy showed a rapid inhibition of binding of fluorochrome-conjugated mAb CD41 and c7E3 concomitant with a reduction in platelet aggregation which was restored in part in the days after termination of abciximab infusion. Induction of ligand-induced binding sites on GPIIb-IIIa was increased in patients receiving abciximab. The expression of ligand-induced binding sites correlated inversely with platelet count. No significant change in platelet membrane markers were found in the heparin group. In vitro studies showed that abciximab induces ligand-induced binding sites on isolated platelets and on nuclear cells bearing recombinant GPIIb-IIIa. Abciximab rapidly achieves GPIIb-IIIa receptor blockade after coronary stent placement that might be beneficial in high-risk settings to bridge the delayed action of ticlopidine. Significant alterations of platelet membrane glycoproteins during GPIIb-IIIa antagonism might contribute to development of acute profound thrombocytopenia.
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PMID:Effect of glycoprotein IIb-IIIa receptor antagonism on platelet membrane glycoproteins after coronary stent placement. 986 73

We report a complication observed in a 77-year-old man admitted to another hospital for "de novo" angina, in which coronary angiography showed a proximal 65% stenosis of the left anterior descending artery. The patient was medically stabilized, but one month later he developed unstable angina that was not controlled by heparin, nitrate and calcium antagonist infusions. Therefore, he was started on ReoPro (0.25 mg/kg bolus and 10 micrograms/min infusion) but because of persisting symptoms, he was transferred to our unit for urgent PTCA. Angioplasty plus stenting was successful and angina disappeared. The ReoPro infusion was stopped (6 hours after it had been started) for mild oral bleeding. Blood analysis was normal (including platelet count) except for the activated partial thromboplastin (PTT) and prothrombin (PT) time, which exceeded the laboratory limits of determination. Consequently, heparin infusion was also stopped. Eight hours after PTCA, he suddenly developed hypotension, bradycardia and loss of consciousness. The echocardiogram revealed a large pericardial effusion with diastolic collapse of the right cardiac chambers. The patient was treated with volume expanders, plasma and platelet units in an attempt to reestablish a normal hemodynamic pattern and normal platelet function. Elective pericardiocentesis was performed 24 hour later, with drainage of 800 ml of hematic effusion. Severe hemorrhagic complication was induced by ReoPro despite a normal platelet count. This was successfully counteracted with plasma and platelet infusion.
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PMID:[Cardiac tamponade after coronary angioplasty induced by treatment with ReoPro]. 1032 29

We present our single-center experience of rotational atherectomy (RA) in the first 1,000 consecutive patients divided arbitrarily into three different time periods corresponding to significant changes in technique or equipment for RA. Period I (August 1994 to April 1995; 172 cases) is characterized by early experience, longer ablation, and frequent use of intra-aortic balloon pump; period II (May 1995 to January 1996; 254 cases) is characterized by short ablation runs (20-30 sec) and use of rotaflush; period III (February 1996 to February 1997; 574 cases) is characterized by ReoPro use, neosynephrine boluses to avoid hypotension, and rota floppy wire and flexible shaft burrs. The procedural success rate has improved and complication rates have progressively declined over these three time periods. The incidence of lesion complexity (long and type C lesions) and patients with unstable rest angina have increased over these time periods of RA. Therefore, modification in procedural techniques and equipment over time have made RA a safe technique despite its use in very complex lesion subsets.
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PMID:Rotational atherectomy: improved procedural outcome with evolution of technique and equipment. Single-center results of first 1,000 patients. 1034 28

In order to evaluate the efficacy and safety of coronary stenting, we reviewed the first 32 consecutive patients (34 vessels) who underwent elective coronary stenting during the period August 1999 to August 2000 inclusive at the Digital Lab installed at the Eric Williams Medical Sciences Complex, Trinidad and Tobago. Aspirin, heparin and ticlopidine were used routinely. Abciximab was used in selected cases (38%). The mean age of patients was 55 +/- 10 years. Eighty-one per cent were male, 52% were hypertensive and 21% were diabetic. Sixty-five per cent had severe angina. Prior Coronary Artery Bypass Grafting (CABG) was performed in 3% and previous Percutaneous Transluminal Coronary Angioplasty (PTCA) in 3%. Multivessel disease was present in 43%. The mean left ventricular ejection fraction was 53 +/- 12%. The culprit lesion was located in either the native left anterior descending (LAD) coronary artery (53%), right coronary artery (RCA) (31%), circumflex artery 13% and saphenous vein graft (3%). The mean baseline diameter stenosis was 91 +/- 9% and this was reduced to 13 +/- 33% after stenting. Procedural success was 100% for 26 partially occluded vs 50% for 8 totally occluded vessels. For the total occlusions, procedural success was inversely related to the duration of the occlusion. There were no cases of death, acute vessel closure, Q-wave myocardial infarction, repeat PTCA or emergent Coronary Artery Bypass Graft (CABG) during and following the procedure. Distal embolization occurred in one patient. The mean duration of hospital stay was one day (for 30 outpatient cases). One patient had recurrence of symptoms with a negative stress test. No patient underwent repeat angiography during the first year of follow-up. Coronary stents were successfully implanted at a tertiary care facility in the Caribbean with low in-hospital morbidity and mortality. Stents markedly reduced the diameter stenosis of the coronary lesion during PTCA. The incidence of clinical restenosis was low. Coronary revascularisation can be successfully achieved by coronary stenting in the Caribbean.
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PMID:Stenting of partial and total coronary occlusions in Trinidad and Tobago. 1139 82

During the last 10 years a new group of drugs was developed--platelet glycoprotein IIb/IIIa blockers that is nowadays largely and efficiently used as for the prevention of percutaneous coronary intervention complications as well as in the treatment of acute coronary syndromes. In the period February-June 2000--19 patients (18 males, 1 female, of average age 53.3 years) were administered Abciximab in the bolus dose of 10 mg immediately before the intervention and afterwards 10 mg by 12-hour infusion. All patients received aspirin and ticlopidine hydrochloride if the stent was introduced and heparin by the standard protocol. Elective intervention was done in 17 patients (non-Q infarction in 3 patients, unstable angina pectoris in 5 patients, postinfarction angina pectoris in 2 patients, acute myocardial infarction at least 1 month before the intervention in 6 patients and 1 patient with myocardiopathy) and in 2 patients the intervention was performed during the myocardial infarction. In 15 patients (79%) intracoronary stent was introduced and in 5 patients (21%) the intervention was performed on 2 arteries. Maximal immediate effect of the dilatation was achieved in 18 patients (94.7%). In the first 60 days of the follow-up 1 patient (5%) died of some other disease, and in no patients symptomatic myocardial ischemia was found. No adverse effects were observed.
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PMID:[Clinical study of administration of abciximab--a monoclonal antibody to platelet glycoprotein IIb/IIIa in percutaneous intracoronary interventions]. 1176 14

Randomized clinical trials have evidently shown that the addition of thienopyridines or abciximab to standard aspirin results in a significant reduction of ischaemic complications after coronary stent implantation. A head-to-head comparison of these antithrombotic drug regimens during coronary intervention is, however, lacking, and this was the main aim of the present study. Thirty-nine patients with angina pectoris who were scheduled for coronary stent implantation were assigned to either group 1 (160 mg aspirin + 500 mg ticlopidine post-stent), group 2 (160 mg aspirin + abciximab + 500 mg ticlopidine post-stent) or group 3 (160 mg aspirin + loading dose (375/450 mg) clopidogrel pre-stent and 75 mg clopidogrel post-stent). A loading dose of 450 mg clopidogrel was found to be more effective than the standard loading dose of 375 mg. Platelet aggregation induced by 4 micromol/l adenosine diphosphate (ADP) was assessed in samples collected before intervention and 10 min, 4 h and 20 h after intervention. Before intervention, a moderate antiplatelet effect because of aspirin intake was observed (ADP aggregation level, +/- 50%) in all study groups. After intervention, platelet aggregation tended to be enhanced in group 1 while it was strongly inhibited in the groups pre-treated with clopidogrel or abciximab: ADP induced an aggregation level early after intervention of 60 +/- 12% in group 1 (ticlopidine post-stenting) versus 30 +/- 10% in group 3 (loading dose clopidogrel) versus 3 +/- 6% in group 2 (abciximab). Abciximab achieved a more complete inhibition of aggregation than clopidogrel (P = 0.007). The overall complication rate was low with only one major bleeding and one death due to side-branch occlusion with re-infarction occurring, both in the abciximab group. Platelet aggregation during coronary intervention is strongly inhibited by both abciximab and by high loading dose of clopidogrel. Although abciximab showed a stronger antiplatelet effect than clopidogrel, it remains to be established whether this ex vivo superiority of abciximab also translates into an overall clinical benefit in patients with elective stent implantation.
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PMID:Comparison of antiplatelet effect of loading dose of clopidogrel versus abciximab during coronary intervention. 1203 92

Abciximab therapy improves clinical outcomes after percutaneous interventions for de novo coronary artery disease. We sought to determine whether clinical outcomes after percutaneous intervention for in-stent restenosis are affected by abciximab administration. Between January 1996 and July 1999, 322 consecutive patients underwent percutaneous intervention for in-stent restenosis; 157 patients received abciximab and 165 patients were treated without abciximab based on operator discretion. Baseline clinical and angiographic variables and type of percutaneous intervention were recorded. Follow-up information was obtained and clinical endpoints were recorded. A multivariate analysis was performed to determine the independent variables associated with adverse clinical outcomes. Baseline clinical and angiographic variables were similar in both groups. Patients who received abciximab were more likely to be treated with rotational atherectomy and less likely to have only balloon angioplasty or repeat stenting. Mean follow-up duration was 19 +/- 12 months. There were no significant differences in the incidence of angina/myocardial infarction (29% vs. 30%; P = 0.9), target vessel revascularization (18% vs. 21%; P = 0.5), death (8% vs. 7%; P = 0.4), or major adverse cardiovascular events (38% vs. 39%; P = 0.9) in both groups. Abciximab administration was not an independent variable associated with adverse outcomes. In this observational study, clinical outcomes after percutaneous intervention for in-stent restenosis did not seem to be affected by abciximab administration. Randomized trials are needed to identify the role of platelet glycoprotein IIb/IIIa inhibitors in the management of in-stent restenosis.
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PMID:Abciximab administration and clinical outcomes after percutaneous intervention for in-stent restenosis. 1211 10


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