Journal of thrombosis and thrombolysis
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J. Thromb. Thrombolysis · Jul 2012
Randomized Controlled Trial Multicenter Study Comparative StudyBleeding-associated outcomes with preoperative clopidogrel use in on- and off-pump coronary artery bypass.
Clopidogrel use prior to coronary artery bypass graft surgery in patients presenting with acute coronary syndromes is associated with a greater incidence of procedural related morbidity. We studied the impact of clopidogrel pre-treatment in patients undergoing off-pump versus on-pump coronary revascularization. This report describes a post hoc analysis of 431 on-pump and 165 off-pump cases from a retrospective multicenter study of the impact of preoperative (within 5 days) clopidogrel use on bleeding related outcomes and surgical reintervention. ⋯ After multivariable adjustment, the odds ratio of major bleeding (1.76, 95% confidence interval 0.88-3.52 on-pump; 2.37, 95% confidence interval 1.06-5.30 off-pump) and reoperation (4.52, 95% confidence interval 0.58-36.6 in on-pump; 7.05, 95% confidence interval 0.82-60.5 in off-pump) was increased in clopidogrel-treated patients compared to no clopidogrel. Major bleeding and reoperation did not differ significantly between patients undergoing on- or off-pump surgery. Clopidogrel treatment within 5 days prior to surgery increased the risk of bleeding and reoperation in all CABG patients irrespective of whether surgery was performed on- or off-pump.
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J. Thromb. Thrombolysis · Jul 2012
Randomized Controlled Trial Multicenter StudyPharmacodynamic effects of cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials.
Cangrelor is an intravenous antagonist of the P2Y(12) receptor characterized by rapid, potent, predictable, and reversible platelet inhibition. However, cangrelor was not superior to clopidogrel in reducing the incidence of ischemic events in the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. A prospectively designed platelet function substudy was performed in a selected cohort of patients to provide insight into the pharmacodynamic effects of cangrelor, particularly in regard to whether cangrelor therapy may interfere with the inhibitory effects of clopidogrel. ⋯ A rapid platelet inhibitory effect was achieved during cangrelor infusion and a rapid offset of action after treatment discontinuation. This CHAMPION platelet function substudy represents the largest pharmacodynamic experience with cangrelor, demonstrating its potent P2Y(12) receptor inhibitory effects, and rapid onset/offset of action. Although there was no significant pharmacodynamic interaction when transitioning to clopidogrel therapy, further studies are warranted given that enrollment in this study was limited due to premature interruption of the main trial.
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J. Thromb. Thrombolysis · Aug 2011
Randomized Controlled Trial Multicenter StudyChromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban--an oral, direct and selective factor Xa inhibitor.
An ability to readily determine an anticoagulant effect with an emerging class of direct, active site, oral factor Xa inhibitors is viewed by the medical community as attractive and by some as an absolute requirement for their use in clinical practice. We performed a pharmacokinetic and pharmacodynamic substudy in APPRAISE-1-a study of apixaban in patients with acute coronary syndrome(ACS). A total of 1691 patients had blood sampled for apixaban plasma concentrations using mass spectrometry/high performance liquid chromatography and anti-Xa activity using a chromogenic assay employing either low molecular weight heparin or apixaban as reference standards. ⋯ The correlations for each method were equally strong at low (<100 ng/ml) (r = 0.86, P < 0.0001; r = 0.85, P < 0.0001), intermediate(100-200 ng/ml) (r = 0.73, P < 0.0001; r = 0.69, P < 0.0001) and high (>200 ng/ml) (r = 0.91, P < 0.0001; r = 0.91, P < 0.0001) plasma concentrations of apixaban, respectively. Our pharmacokinetic and pharmacodynamic substudy suggests that an apixaban-mediated anticoagulant effect can be detected even at very low plasma concentrations using a standard laboratory chromogenic anti-Xa assay with either LMWH or apixaban calibrators. While establishing parameters for safety and efficacy will require further investigation, an ability to discern the presence of a drug effect may provide clinically useful information.
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J. Thromb. Thrombolysis · May 2011
Randomized Controlled Trial Multicenter StudyExtended-duration rivaroxaban thromboprophylaxis in acutely ill medical patients: MAGELLAN study protocol.
Patients with acute medical illnesses are at increased risk of venous thromboembolism (VTE), a significant cause of morbidity and mortality. Thromboprophylaxis is recommended in these patients but questions remain regarding the optimal duration of therapy. The aim of this study is to determine whether oral rivaroxaban is non-inferior to standard-duration (approximately 10 days) subcutaneous (s.c.) enoxaparin for the prevention of VTE in acutely ill medical patients, and whether extended-duration (approximately 5 weeks) rivaroxaban is superior to standard-duration enoxaparin. ⋯ As of July 2010, 8,101 patients from 52 countries have been randomized. These patients have a broad range of medical conditions: approximately one-third were diagnosed with acute heart failure, just under one-third were diagnosed with acute infectious disease, and just under one-quarter were diagnosed with acute respiratory insufficiency. MAGELLAN will determine the efficacy, safety, and pharmacological profile of oral rivaroxaban for the prevention of VTE in a diverse population of medically ill patients and the potential of extended-duration therapy to reduce incidence of VTE.
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J. Thromb. Thrombolysis · Jan 2011
Multicenter StudyImprovement of hemodialysis catheter function with tenecteplase: a phase III, open-label study: TROPICS 4.
Hemodialysis (HD) catheters are prone to thrombotic occlusion. We evaluated tenecteplase, a thrombolytic, for the treatment of dysfunctional HD catheters. Patients with tunneled HD catheters and blood flow rate (BFR) <300 mL/min received open-label tenecteplase (2 mg/lumen) for a 1 h intracatheter dwell. ⋯ Reported targeted adverse events included five catheter-related bloodstream infections and one thrombosis. No intracranial hemorrhage, major bleeding, embolic events, or catheter-related complications were reported. Tenecteplase administered as a 1 h or 1 h plus extended dwell was associated with improved HD catheter function in the TROPICS 4 trial.