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Biomedical subjects

J J Ferguson

Publications and source records attributed to J J Ferguson.

At least 19 recordsLinked to original sources
PubMed2001

Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention.

OBJECTIVES: The goal of this study was to test: 1) if platelet glycoprotein IIb/IIIa (GP IIb/IIIa) blockade with abciximab bolus plus 12-h infusion reduces mortality after percutaneous coronary intervention (PCI); 2) if prevention of early myocardial infarction (MI) after PCI is a mechanism for reducing mortality; and 3) for risk factors for mortality after PCI. BACKGROUND: Studies of PCI suggest that MI after intervention is predictive of mortality. Abciximab, a platelet GP IIb/IIIa receptor inhibitor, has consistently reduced the incidence of MI among PCI patients in several trials. The presumed mechanism is prevention of platelet thrombus associated with vessel wall injury and downstream embolization into the microcirculation. METHODS: In eight trials, 5,154 patients were randomized to a regimen comprising conventional therapy plus a bolus of abciximab within 1 h before PCI followed by a 12-h infusion; 4,136 controls were randomized to conventional therapy alone. Patient follow-up from six months to three years was available. Survival differences are examined using proportional hazards regression and survival curves. RESULTS: A hazard ratio of 0.71 (95% confidence interval 0.57 to 0.89; p = 0.003) suggests a mortality benefit with abciximab. The absolute reduction in mortality was estimated to be 0.5% through 30 days, 0.7% through six months, 0.9% through one year and 1.8% through three years. Early MI explained 18% of the observed mortality benefit at one year. Multivariate regression suggests that patients with advanced cardiovascular disease may derive the greatest mortality benefit from abciximab. CONCLUSIONS: The evidence from 9,290 randomized PCI patients shows a mortality benefit provided by abciximab bolus plus 12-h infusion.

Abciximab↗
PubMed2001

Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention.

Randomized controlled trials of patients with non-ST segment elevation acute coronary syndromes have established the superiority of enoxaparin (versus unfractionated heparin) for reducing adverse ischemic outcomes. Furthermore, adjunctive abciximab therapy during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. Since algorithms for integrating these pharmacotherapies have not been determined, patients undergoing elective PCI were enrolled into 2 distinct and separate studies conducted by the National Investigators Collaborating on Enoxaparin (NICE) study groups (NICE 1 and NICE 4 studies). Patients in NICE 1 were administered enoxaparin 1.0 mg/kg intravenously (without abciximab) and those enrolled in NICE 4 were administered a reduced dose (0.75 mg/kg) of enoxaparin in combination with standard-dose abciximab intravenously during PCI. Bleeding events and ischemic outcomes assessed in-hospital and at 30-days post-PCI were infrequent with either pharmacologic regimen. In the dose regimens studied, enoxaparin with or without abciximab appears to provide safe and effective anticoagulation during PCI. The combination of reduced-dose enoxaparin and abciximab was associated with a low incidence of adverse outcomes (bleeding or ischemic events). Additional studies may be required to establish the relative safety and efficacy of this new adjunctive pharmacologic strategy when compared with the combination of low-dose, weight-adjusted unfractionated heparin and abciximab.

Abciximab↗
PubMed2000

Endoluminal reconstruction of the arterial wall with endothelial cell/glue matrix reduces restenosis in an atherosclerotic rabbit.

OBJECTIVES: The objectives of this study were 1) to improve the attachment of reimplanted endothelial cells (EC) using a fibrin glue, and 2) to assess the impact of endothelial reseeding on restenosis eight weeks after balloon angioplasty. BACKGROUND: A possible mechanism contributing to restenosis after balloon angioplasty is the loss of the EC lining. Previous attempts to reseed EC had little effect due to rapid loss of the seeded cells. METHODS: Twelve atherosclerotic rabbits were subjected to angioplasty of iliac arteries and reseeding procedure. One iliac artery was subjected to EC/glue reconstruction and a contralateral site to EC seeding without glue. The animals were sacrificed after 4 h. In another series 12 rabbits were treated in the same fashion and were restudied at eight weeks. Additionally, in 10 animals one iliac was subjected to glue treatment, and another served as control. RESULTS: Histological examination demonstrated the ability of this method to reattach the EC/glue matrix circumferentially to 68.0 +/- 6.7% of the arterial wall in comparison with 13.5 +/- 3.9% reattachment after EC seeding. Morphometry at eight weeks showed that the lumen area was significantly greater in the EC/glue group (1.23 +/- 0.35 mm2) than in the EC seeding alone (0.65 +/- 0.02 mm2) and 0.72 +/- 0.41 mm2 in the glue group. This was principally accounted for by the statistically significant differences in the intimal area (0.76 +/- 0.18 mm vs. 1.25 +/-0.26 mm2 and 1.01 +/- 0.53 mm2, respectively). CONCLUSIONS: The attachment of EC after angioplasty can be greatly improved with fibrin glue matrix. The near 70% endothelial coverage achieved by this method resulted in a significant reduction of restenosis in atherosclerotic rabbit.

Angioplasty, Balloon↗
PubMed2000

New insights in cardiac structural changes in patients with Fabry's disease.

BACKGROUND: Fabry's disease is an X-linked recessive genetic deficiency of the enzyme alpha-galactosidase leading to the pathologic intracellular deposition of neutral glycosphingolipids. Although cardiac involvement is frequent, there is controversy regarding the character of the associated left ventricular (LV) changes and the severity of valvular involvement. METHODS: Clinical evaluation (disease severity scaling, laboratory tests, and echocardiography) was performed in 13 hemizygous men (mean age 39 +/- 10 years) and 17 heterozygous women (mean age 35 +/- 19 years). RESULTS: LV hypertrophy (LVH) was frequent in subjects older than 30 years, more often in men (61%) than in women (18%, P <.001). The degree of LVH was independently associated with age and the logarithm of alpha-galactosidase activity (r(2) = 0.70, P <.001). The predominant LV geometric patterns were concentric LVH and remodeling, both present in 11 subjects (36%). Three patients had an asymmetric septal hypertrophy mimicking hypertrophic cardiomyopathy. In most subjects with LVH, the systolic function was normal and severe diastolic dysfunction (restrictive pattern) was not noted. Minor structural abnormalities of the mitral valve were found in 17 subjects (57%). The aortic valve was affected in 14 patients (47%). Valvular abnormalities were frequently accompanied by regurgitation of minor to mild degree. The presence of LVH or valvular changes was associated with increased disease severity. CONCLUSIONS: Echocardiographically detectable cardiac involvement is frequent with Fabry's disease, particularly in older subjects, and more pronounced in affected hemizygous men than in heterozygous women. LVH is frequently observed but usually not associated with significant systolic or restrictive diastolic dysfunction. Concentric LVH and remodeling appear to be the major manifestations of LV structural alteration. The frequently noted valvular abnormalities were not associated with a significant degree of regurgitation. Valvular and especially LV structural changes may serve as a useful marker of disease severity.

Adolescent↗
PubMed2000

Combining low-molecular-weight heparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: the NICE 3 story. National Investigators Collaborating on Enoxaparin.

In recent years, a number of new therapies have become available that have significantly improved the care of patients with acute coronary syndromes (ACS). A number of studies have documented the significant superiority of the low-molecular-weight heparin (LMWH), enoxaparin, over unfractionated heparin (UFH) in the treatment of ACS. However, there are insufficient data regarding the safety of using LMWH in combination with glycoprotein (GP) IIb/IIIa antagonists. The NICE 3 study is an open-labeled, non-randomized, observational study examining the feasibility, safety, and preliminary efficacy of the LMWH, enoxaparin, in combination with each of the three commercially available GP IIb/IIIa antagonists in ACS patients. Approximately 600 patients at 45 clinical centers in North America will be divided between the three arms of the trial, representing each of the three GP IIb/IIIa antagonists. Once therapy is initiated, patients will receive no UFH (unless they require a coronary artery bypass graft) and will continue treatment even if invasive cath lab procedures are necessary. NICE 3 builds on the previous experiences of NICE 1 and NICE 4 with LMWH in the cath lab (with or without GP IIb/IIIa antagonists) to more aggressively extend the use of LMWHs into the medical management of ACS patients.

Abciximab↗
PubMed1999

Differences between men and women in the management of unstable angina pectoris (The GUARANTEE Registry). The GUARANTEE Investigators.

Few data are available in prospectively collected cohorts of patients with unstable angina pectoris or on the use of appropriate medications or interventions. Accordingly, we evaluated 2,948 consecutive patients with unstable angina admitted to 35 hospitals in the United States in 1996, and comparing men and women (39% of the patients were women). Differences were seen in coronary risk profiles with a higher incidence of systemic hypertension, diabetes mellitus, and a family history of coronary disease in women. Women were less likely to receive Agency for Health Care Policy Research (AHCPR) recommended pharmacologic treatment than men. Cardiac catheterization, coronary angioplasty, and bypass was performed less often in women compared with men (44% vs. 53%, p = 0.002; 12% vs. 18%, p = 0.02; 7% vs. 10%, p = 0.001, respectively). At catheterization, women were more likely to have no significant coronary artery disease (25% vs. 14%, p = 0.001). Although fewer women than men fulfilled the AHCPR criteria for cardiac catheterization (54% vs. 64%, p = 0.001), a similar rate of men and women with positive criteria underwent catheterization and angioplasty. However, fewer women with positive criteria underwent bypass surgery (36% vs. 46%, p = 0.03). More men "ruled-in" for a myocardial infarction at admission (13% vs. 8%, p = 0.001), but there was no difference in recurrent angina, in-hospital myocardial infarction, or death. Despite different epidemiologic profiles and less evidence of coronary artery disease by noninvasive and invasive tests, women and men had similar outcomes.

Adult↗
PubMed1999

Platelet-endothelial interactions in atherothrombotic disease: therapeutic implications.

The role of the platelet and the endothelium in the pathogenesis of atherosclerosis and subsequent ischemic events has been the subject of extensive investigation. Arterial sites where endothelial function is severely impaired are often the sites of atheroma development. Lesion evolution impairs endothelial function, leading to a self-perpetuating cycle of growth. During early lesion development, overt thrombotic events are rare. However, rupture of an advanced, necrotic plaque or intimal ulceration triggers arterial thrombosis, at which point the importance of platelet function may be seen clearly. The Antiplatelet Trialists' Collaboration meta-analysis demonstrated the benefit of antiplatelet therapy to patients with atherosclerotic disease. Aspirin is the most widely studied agent and is considered the standard of antiplatelet therapy. Newer agents that intervene at different stages of the platelet activation pathway have been developed. Clopidogrel, a new adenosine diphosphate receptor antagonist, is more effective than aspirin in reducing vascular events in patients with prior myocardial infarction, stroke, or established peripheral arterial disease. The glycoprotein IIb-IIIa antagonists such as abciximab have proven effective in the setting of active arterial thrombosis and percutaneous revascularization, but their value in secondary prevention remains unknown. All patients with atherosclerosis should be treated with an antiplatelet drug. Current evidence suggests that either aspirin or clopidogrel are appropriate first-line agents. There is urgent need for an analysis of the risk/benefit ratio in various populations and clinical settings to determine the most appropriate type and intensity of therapy for a given patient.

Animals↗
PubMed1999

Trials of glycoprotein IIb-IIIa inhibitors in non-ST-segment elevation acute coronary syndromes: applicability to the practice of medicine in the United States.

Platelet-mediated thrombosis has been recognized as the primary pathophysiologic mechanism of acute coronary syndromes (ACS) and acute complications of percutaneous coronary intervention (PCI). Despite the clinical efficacy of the two most widely used antithrombotic agents, aspirin and heparin, each of them has significant therapeutic limitations. As a result, thrombosis and clinical events may occur despite the use of aspirin and heparin. The discovery that the platelet glycoprotein (GP) IIb-IIIa represents the final common pathway to platelet aggregation and the growing recognition of the key role of platelets in the progression of thrombosis prompted the development of several GP IIb-IIIa inhibitors as a potentially more effective form of antithrombotic therapy. Numerous trials of various GP IIb-IIIa inhibitors as adjuncts to PCI have strongly supported this hypothesis. The subject of this supplement is the review of more recent evaluations of GP IIb-IIIa inhibitors in the context of various treatment strategies for the management of patients with unstable angina or non-ST-segment elevation myocardial infarction, collectively known as non-ST-segment elevation ACS. Appropriate translation of these trials into clinical practice requires not only the knowledge of the trials' results but also the understanding of the design of individual studies, most notably the entry criteria and patient management strategies.

Acute Disease↗