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- Guigliano, Robert P, et al.
(author)
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Early versus delayed, provisional eptifibatide in acute coronary syndromes.
- 2009
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In: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 360:21, s. 2176-2190
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Journal article (peer-reviewed)abstract
- Background Glycoprotein IIb/IIIa inhibitors are indicated in patients with acute coronary syndromes who are undergoing an invasive procedure. The optimal timing of the initiation of such therapy is unknown. Methods We compared a strategy of early, routine administration of eptifibatide with delayed, provisional administration in 9492 patients who had acute coronary syndromes without ST-segment elevation and who were assigned to an invasive strategy. Patients were randomly assigned to receive either early eptifibatide (two boluses, each containing 180 µg per kilogram of body weight, administered 10 minutes apart, and a standard infusion 12 hours before angiography) or a matching placebo infusion with provisional use of eptifibatide after angiography (delayed eptifibatide). The primary efficacy end point was a composite of death, myocardial infarction, recurrent ischemia requiring urgent revascularization, or the occurrence of a thrombotic complication during percutaneous coronary intervention that required bolus therapy opposite to the initial study-group assignment ("thrombotic bailout") at 96 hours. The key secondary end point was a composite of death or myocardial infarction within the first 30 days. Key safety end points were bleeding and the need for transfusion within the first 120 hours after randomization. Results The primary end point occurred in 9.3% of patients in the early-eptifibatide group and in 10.0% in the delayed-eptifibatide group (odds ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P=0.23). At 30 days, the rate of death or myocardial infarction was 11.2% in the early-eptifibatide group, as compared with 12.3% in the delayed-eptifibatide group (odds ratio, 0.89; 95% CI, 0.79 to 1.01; P=0.08). Patients in the early-eptifibatide group had significantly higher rates of bleeding and red-cell transfusion. There was no significant difference between the two groups in rates of severe bleeding or nonhemorrhagic serious adverse events. Conclusions In patients who had acute coronary syndromes without ST-segment elevation, the use of eptifibatide 12 hours or more before angiography was not superior to the provisional use of eptifibatide after angiography. The early use of eptifibatide was associated with an increased risk of non–life-threatening bleeding and need for transfusion.
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- Harrington, Robert A., et al.
(author)
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The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial : study design and rationale
- 2009
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In: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 158:3, s. 327-334
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Journal article (peer-reviewed)abstract
- Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies.
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- Morrow, DA, et al.
(author)
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Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)-TIMI 50 trial
- 2009
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In: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 158:3, s. 335-341
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Journal article (peer-reviewed)abstract
- BACKGROUND: Thrombin potently activates platelets via interaction with the protease-activated receptor 1. SCH 530348 is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin via antagonism of the protease-activated receptor 1. Because SCH 530348 does not interfere with other pathways for hemostasis, it is possible that SCH 530348 reduces thrombosis with less increase in bleeding than do other potent antiplatelet agents. STUDY DESIGN: TRA 2 degrees P-TIMI 50 is a phase III, randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of SCH 530348 during long-term treatment of patients with established atherosclerotic disease receiving standard therapy (up to 27,000). Eligible patients with a history of myocardial infarction, ischemic stroke, or peripheral arterial disease are randomized 1:1 to SCH 530348 2.5 mg daily or matched placebo until the end of study. Randomization is stratified by the qualifying disease and planned use of a thienopyridine. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, or urgent coronary revascularization. The major secondary end point is the composite of cardiovascular death, myocardial infarction, or stroke. The evaluation of long-term safety includes bleeding defined by the GUSTO and TIMI criteria. Recruitment began in September 2007. The trial will continue until 2,279 primary end points and 1,400 secondary end points are recorded with expected completion in 36 to 44 months from first enrollment. CONCLUSIONS: TRA 2 degrees P-TIMI 50 is evaluating whether a new approach to platelet inhibition via interruption of thrombin-mediated platelet activation reduces major cardiovascular events with a favorable safety profile in patients with established atherosclerosis.
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- Perri, S., et al.
(author)
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Magnetic turbulence in space plasmas : Scale-dependent effects of anisotropy
- 2009
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In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 114, s. A02102-
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Journal article (peer-reviewed)abstract
- The presence of a background magnetic field induces anisotropy in magnetic turbulence. Understanding properties of anisotropy is important to characterize turbulence power spectrum. This paper presents a case study of anisotropy by using a minimum variance analysis, in three different regions of the heliosphere, namely in the solar wind, and in the Earth's foreshock and magnetosheath behind a quasiparallel bow shock. A strong anisotropy is found in all cases, with very interesting cross-scale effects at the ion cyclotron frequency. In particular, (1) the eigenvalues of the variance matrix have a strong intermittent behavior, with very high localized fluctuations below the ion cyclotron scale. As a consequence the probability distribution functions are almost Gaussian5 above the ion cyclotron scale and become power laws at smaller scales; (2) the minimum variance direction is almost parallel to the background magnetic field at scales larger than the ion cyclotron scale in the solar wind and in the foreshock, while their probability density functions become broader at smaller scales. In the magnetosheath the minimum variance direction exhibits a tendency to become nearly perpendicular to the large-scale magnetic field below the ion cyclotron scale.
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- Servidio, Sergio, et al.
(author)
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Compressible turbulence in Hall Magnetohydrodynamics
- 2007
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In: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 55:15, s. 2239-2243
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Journal article (peer-reviewed)abstract
- By direct numerical simulations we investigate the nonlinear dynamics of a compressible Hall Magnetohydrodynamic (MHD) plasma. At small scales, where the Hall effect dominates, we found an increase of the compressibility of the system and the breakdown of the strong link between velocity and magnetic fields, typical of usual MHD. Moreover, we find that small-scale fluctuations are characterized by an anti-correlation between density and magnetic field intensity. These features characterize the excitation. of a quasi-perpendicular magnetosonic turbulence that can be interpreted as the small-scale signature of the break-down of the MHD nonlinear energy cascade due to Hall effect. Fluctuations with the same properties, based on measurements by Cluster spacecraft in space plasma turbulence during different magnetopause crossings, have been recently observed.
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