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Biomedical subjects

J J Ferguson

Publications and source records attributed to J J Ferguson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Fundamentals of coagulation and glycoprotein IIb/IIIa receptor inhibition.

An understanding of the coagulation process and the role of platelets is essential to recognizing the shortcomings of older anticoagulant therapies and appreciating the clinical potential of newer forms of antiplatelet and anticoagulant therapy for acute coronary syndromes. The anticoagulant actions of heparin are severely limited by dependence on antithrombin III, neutralization by platelet factor 4, and the resistance of clot-bound thrombin and platelet membrane-bound factor Xa to the heparin-antithrombin III complex. Unlike heparin, the direct thrombin inhibitors (such as hirudin) are active against both circulating and clot-bound thrombin. However, in recent clinical trials they have not resulted in major improvements in patient outcome. Another new class of drugs, the glycoprotein IIb/IIIa receptor antagonists, blocks the final common pathway of platelet aggregation and is capable of preventing platelet accumulation at sites of injury. The net effect is a dramatic reduction in the amount of platelet membrane available to support the process of coagulation. Clinical trials with the glycoprotein IIb/IIIa inhibitors have suggested that this class of agents may be particularly effective in reducing the thrombotic complications associated with coronary interventional procedures and may be useful in the treatment of acute coronary syndromes.

Acute Disease↗
PubMed1998

Safe use of platelet GP IIb/IIIa inhibitors.

The platelet membrane glycoprotein IIb/IIIa receptor inhibitor abciximab is used for the treatment of patients undergoing high-risk percutaneous coronary interventions and is used in approximately one third of coronary interventions in the United States and a growing number of procedures in Europe. Recent clinical trials have shown that this potent antiplatelet agent significantly reduces the incidence of death and nonfatal myocardial infarction and the need for revascularization. With expanding experience since the commercial release of abciximab in February 1995, several strategies to enhance the safety of abciximab have emerged. In particular, new data confirm that the risk of bleeding-identified as a concern in the original EPIC trial-can be substantially reduced through the use of low-dose adjunctive heparin, early sheath removal, and fastidious postprocedure vascular access site care. Other recommendations for enhancing the safety of potent antiplatelet agents in a variety of clinical situations are provided. The following article reflects insights regarding the safety of glycoprotein IIb/IIIa inhibitors expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997 This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation.

Abciximab↗
PubMed1998

Influence of insurance type on the use of procedures, medications and hospital outcome in patients with unstable angina: results from the GUARANTEE Registry. Global Unstable Angina Registry and Treatment Evaluation.

OBJECTIVES: The purpose of this study was to investigate whether or not there is an association between managed care insurance and the delivery and outcome of care in patients presenting with unstable angina. BACKGROUND: The proportion of U.S. patients with managed care health insurance is increasing. This may be associated with recent improvements in the control of health care costs. It is unknown whether or not there is a difference in process of care in angina patients presenting with managed care versus fee-for-service health insurance. METHODS: We compared baseline characteristics, process and outcome of care in 636 patients with managed care insurance (MC) and 1,404 patients with fee-for-service (FFS) insurance who presented with unstable angina to 35 hospitals participating in the global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry. RESULTS: Although, there was little difference in baseline characteristics and hospital treatments between cohorts, MC patients were more likely to be discharged on guideline-recommended medications (aspirin and beta-adrenergic blocking agents). In addition, FFS patients were more likely to undergo cardiac catheterization (odds ratio = 1.25 95% confidence interval = 1.1 to 1.5), but not revascularization during the hospitalization. There was no difference in hospital mortality (0.9% versus 1.2% in MC versus FFS; p = 0.60). CONCLUSIONS: In patients admitted with suspected unstable angina, MC patients are less likely to undergo coronary angiography, but are more likely to be discharged on indicated medications.

Adrenergic beta-Antagonists↗
PubMed1998

Primary care.

Explore the source record for details and available documents.

Family Practice↗
PubMed1998

Fundamentals of coagulation and glycoprotein IIb/IIIa receptor inhibition.

An understanding of the coagulation process and the role of platelets is essential to recognizing the shortcomings of older anticoagulant therapies and appreciating the clinical potential of newer forms of antiplatelet and anticoagulant therapy for acute coronary syndromes. The anticoagulant actions of heparin are severely limited by dependence on antithrombin III, neutralization by platelet factor 4, and the resistance of clot-bound thrombin and platelet membrane-bound factor Xa to the heparin-antithrombin III complex. Unlike heparin, the direct thrombin inhibitors (such as hirudin) are active against both circulating and clot-bound thrombin. However, in recent clinical trials they have not resulted in major improvements in patient outcome. Another new class of drugs, the glycoprotein IIb/IIIa receptor antagonists, blocks the final common pathway of platelet aggregation and is capable of preventing platelet accumulation at sites of injury. The net effect is a dramatic reduction in the amount of platelet membrane available to support the process of coagulation. Clinical trials with the glycoprotein IIb/IIIa inhibitors have suggested that this class of agents may be particularly effective in reducing the thrombotic complications associated with coronary interventional procedures and may be useful in the treatment of acute coronary syndromes.

Blood Coagulation↗
PubMed1998

Safe use of platelet GP IIb/IIIa inhibitors.

The platelet membrane glycoprotein IIb/IIIa receptor inhibitor abciximab is used for the treatment of patients undergoing high-risk percutaneous coronary interventions and is used in approximately one third of coronary interventions in the United States and a growing number of procedures in Europe. Recent clinical trials have shown that this potent antiplatelet agent significantly reduces the incidence of death and nonfatal myocardial infarction and the need for revascularization. With expanding experience since the commercial release of abciximab in February 1995, several strategies to enhance the safety of abciximab have emerged. In particular, new data confirm that the risk of bleeding--identified as a concern in the original EPIC trial--can be substantially reduced through the use of low-dose adjunctive heparin, early sheath removal, and fastidious postprocedure vascular access site care. Other recommendations for enhancing the safety of potent antiplatelet agents in a variety of clinical situations are provided. The following article reflects insights regarding the safety of glycoprotein IIb/IIIa inhibitors expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997. This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation.

Abciximab↗
PubMed1997

Sustained platelet glycoprotein IIb/IIIa blockade with oral xemilofiban in 170 patients after coronary stent deployment.

BACKGROUND: Inhibition of platelet aggregation with parenteral glycoprotein (GP) IIb/IIIa receptor blockers can reduce the ischemic complications of angioplasty. Sustained efficacy and safety of protracted GP IIb/IIIa blockade with an orally administered agent have not previously been determined. This study is the first randomized, dose-ranging, single-blind, placebo-controlled trial of xemilofiban, an oral platelet GP IIb/IIIa receptor antagonist, administered to patients after intracoronary stent deployment. The pharmacodynamic efficacy of xemilofiban-induced platelet inhibition and clinical safety of this agent was evaluated during chronic therapy. METHODS AND RESULTS: After elective intracoronary stent deployment, patients were randomized to receive placebo (250 mg ticlopidine P.O. BID) or xemilofiban in doses of 5, 10, 15, or 20 mg P.O. BID. All patients received 325 mg aspirin P.O. QD. Inhibition of ex vivo platelet aggregation in response to 20 micromol/L ADP and 4 microg/mL collagen was measured over time after the initial dose of study drug and at 1 and 2 weeks of chronic therapy. Study drug was discontinued after 2 weeks, and all patients were followed clinically for > or = 30 days. Oral xemilofiban resulted in a dose-dependent inhibition of platelet aggregation in response to both agonists that was sustained through 2 weeks of chronic therapy. Doses of xemilofiban required to achieve > or = 50% inhibition of platelet aggregation were > or = 10 mg, and the duration of inhibition was 8 to 10 hours. No significant hemorrhagic episodes or blood transfusions were observed in this trial. CONCLUSIONS: Oral xemilofiban in doses of > or = 10 mg produced > or = 50% inhibition of platelet aggregation in response to ADP and collagen for 8 to 10 hours after dosing. Platelet inhibition was sustained through 2 weeks of chronic therapy. The optimal duration of oral GP IIb/IIIa blockade to effectively suppress recurrent ischemic events after coronary intervention remains to be determined.

Abciximab↗
PubMed1997

Long-term protection from myocardial ischemic events in a randomized trial of brief integrin beta3 blockade with percutaneous coronary intervention. EPIC Investigator Group. Evaluation of Platelet IIb/IIIa Inhibition for Prevention of Ischemic Complication.

CONTEXT: Abciximab, a monoclonal antibody fragment against the platelet receptor alphaIIb beta3 integrin, prevents platelet aggregation. A randomized, placebo-controlled study showed that abciximab improves outcomes for patients undergoing percutaneous coronary angioplasty at 30 days and at 6 months. OBJECTIVE: To determine whether abciximab improves outcomes 3 years after coronary angioplasty. DESIGN: Double-blind, placebo-controlled, randomized trial. SETTING: A total of 56 academic and community hospitals in the United States. PATIENTS: A total of 2099 high-risk patients undergoing coronary angioplasty were randomized. Sufficient time elapsed for 2.5 years of follow-up among 2001 patients and for 3 years of follow-up among 1599 patients. INTERVENTIONS: Abciximab bolus of 0.25 mg/kg followed by infusion at 10 microg/min for 12 hours; abciximab bolus of 0.25 mg/kg followed by placebo infusion; or placebo bolus followed by placebo infusion. MAIN OUTCOMES MEASURES: The primary outcome was the composite of death, myocardial infarction, or coronary revascularization. Secondary outcomes were death, myocardial infarction, or coronary revascularization individually. Subgroups having refractory unstable angina or evolving myocardial infarction and having different elevations of creatine kinase during initial angioplasty were analyzed. RESULTS: At 3 years, composite end points occurred in 41.1% of those receiving abciximab bolus plus infusion; 47.4% of those receiving abciximab bolus only; and 47.2% of those receiving placebo only (for abciximab bolus plus infusion vs placebo, P=.009). Death occurred in 6.8%, 8.0%, and 8.6%, respectively (for abciximab bolus plus infusion vs placebo, P=.20); myocardial infarction in 10.7%, 12.2%, and 13.6%, respectively (for abciximab bolus plus infusion vs placebo, P=.08); and revascularization in 34.8%, 38.6%, and 40.1%, respectively (for abciximab bolus plus infusion vs placebo, P=.02). Among those with refractory unstable angina or evolving myocardial infarction, death occurred in 5.1%, 9.2%, and 12.7%, respectively (for abciximab bolus plus infusion vs placebo, P=.01). Death rates increased as periprocedural creatine kinase levels increased. CONCLUSIONS: Abciximab bolus with infusion given at the time of coronary angioplasty improves outcomes as long as 3 years after the procedure.

Abciximab↗
PubMed1997

Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]).

Despite the potential for reduced morbidity and mortality, aggressive intervention against mild to moderate hypercholesterolemia in patients with coronary heart disease (CHD) remains controversial and infrequently practiced. Eligible patients in the 2.5-year Lipoprotein and Coronary Atherosclerosis Study were men and women aged 35 to 75 years with angiographic CHD and mean low-density lipoprotein (LDL) cholesterol of 115 to 190 mg/dl despite diet. Patients (n = 429; 19% women) were randomized to fluvastatin 20 mg twice daily or placebo. One fourth of patients were also assigned open-label adjunctive cholestyramine up to 12 g/day because prerandomization LDL cholesterol remained > or = 160 mg/dl. The primary end point, assessed by quantitative coronary angiography, was within-patient per-lesion change in minimum lumen diameter (MLD) of qualifying lesions. Across 2.5 years, mean LDL cholesterol was reduced by 23.9% in all fluvastatin patients (+/- cholestyramine) (146 to 111 mg/dl) and by 22.5% in the fluvastatin only subgroup (137 to 106 mg/dl). Primary end point analysis (340 patients) showed significantly less lesion progression in all fluvastatin versus all placebo patients, deltaMLD -0.028 versus -0.100 mm (p <0.01), and for fluvastatin alone versus placebo alone, deltaMLD -0.024 versus -0.094 mm (p <0.02). A consistent angiographic benefit with treatment was seen whether baseline LDL cholesterol was above or below 160 or 130 mg/dl. Beneficial trends with treatment were also consistently seen in clinical event rates but were not statistically significant. Thus, lipid lowering by fluvastatin in patients with mildly to moderately elevated LDL cholesterol significantly slowed CHD progression.

Adult↗
PubMed1997

Standard versus low-dose weight-adjusted heparin in patients treated with the platelet glycoprotein IIb/IIIa receptor antibody fragment abciximab (c7E3 Fab) during percutaneous coronary revascularization. PROLOG Investigators.

Blockade of the platelet glycoprotein IIb/IIIa receptor by abciximab (c7E3 Fab) during coronary intervention reduces the incidence of ischemic complications, but has been associated with a doubling of the risk for bleeding complications. The present pilot study investigated whether modification of heparin dosing and/or early sheath removal would reduce the hemorrhagic complications associated with abciximab. One hundred three patients undergoing coronary intervention received abciximab (0.25 mg/kg bolus, 10 microg/min infusion for 12 hours) and aspirin and were randomized by a 2 x 2 factorial design to 1 of 2 weight-adjusted heparin doses and to 1 of 2 strategies for heparin discontinuation and vascular sheath removal. In the "standard-dose heparin" group, an initial bolus of 100 U/kg was administered to achieve a procedural activated clotting time (ACT) > or = 300 seconds; in the "low-dose heparin" group, an initial bolus of 70 U/kg was administered without adjustment for ACT. In the "late sheath removal" arm, heparin infusion was continued for the 12-hour duration of abciximab infusion, followed by sheath removal; in the "early sheath removal" group, heparin was stopped after the interventional procedure and sheaths were removed during the abciximab infusion. There were no apparent differences between patients randomized to the different treatment groups with regard to the occurrence of ischemic end points. Rates of bleeding and blood transfusion were reduced by low-dose heparin and early sheath removal and were lowest when both strategies were combined. Reduction and weight adjustment of heparin dose and early sheath removal in the setting of platelet inhibition with abciximab during coronary intervention may be useful in diminishing the incidence of hemorrhagic complications without loss of clinical efficacy.

Abciximab↗
PubMed1996

Effects of integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina. A randomized multicenter trial.

BACKGROUND: Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina. METHODS AND RESULTS: Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms. CONCLUSIONS: Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.

Adult↗