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- Albers, GW, et al.
(författare)
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Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation - A Randomized trial
- 2005
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Ingår i: JAMA: The Journal of the American Medical Association. - 1538-3598. ; 293:6, s. 690-698
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Tidskriftsartikel (refereegranskat)abstract
- Context Inpatients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use. Objective To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism. Design, Setting, and Participants Double-blind, randomized, multicenter trial (20002001) conducted at 409 North American sites, involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors. Interventions Adjusted-dose warfarin (aiming for an international normalized ratio [INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily. Main Outcome Measures The primary end point was all strokes (ischemic or hemorrhagic) and systemic embolic events. The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0% per year according to the intention-to-treat model. Results During 6405 patient-years (mean 20 months) of follow-up, 88 patients experienced primary events. The mean (SD) INR with warfarin (2.4 [0.8]) was within target during 68% of the treatment period. The primary event rate with ximelagatran was 1.6% per year and with warfarin was 1.2% per year (absolute difference, 0.45% per year; 95% confidence interval, -0.13% to 1.03% per year; P<.001 for the pre-defined noninferiority hypothesis). When all-cause mortality was included in addition to stroke and systemic embolic events, the rate difference was 0.10% per year (95% confidence interval, -0.97% to 1.2% per year; P=.86). There was no difference between treatment groups in rates of major bleeding, but total bleeding (major and minor) was lower with ximelagatran (37% vs 47% per year; 95% confidence interval for the difference, -14% to -6.0% per year; P<.001). Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0% of patients treated with ximelagatran, usually within 6 months and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other suggestive case occurred. Conclusions The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.
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- Albers, WM, et al.
(författare)
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Design of novel molecular wires for realizing long-distance electron transfer
- 1997
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Ingår i: Bioelectrochemistry and bioenergetics (Print). - : ELSEVIER SCIENCE SA LAUSANNE. - 0302-4598 .- 1872-8049. ; 42:1, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- Novel heteroarene oligomers, consisting of two pyridinium groups, linked by thiophene units of variable length, thienoviologens, are described as promising candidates for molecular wires. Two representative thienoviologens were coated by adsorption from micromolar concentrations in ethanol onto octadecylmercaptan (ODM)-coated gold electrodes and induced a gradual restoration of the electrochemistry with hexacyanoferrate as a function of molecular wire concentration. Glucose oxidase and choline oxidase showed strong adsorption to these conductive layers, but showed striking differences in adsorption to the different thienoviologen layers. The measurements support the hypothesis that the molecules are incorporated in the ODM layer in a different fashion. Also the complex formation of an engineered azurin redox protein with water-soluble pyridyl ligands is presented in relation to a possible application of the thienoviologens as conductive spacers, in which the contact with the redox protein is achieved via complex formation with a free pyridine nitrogen. (C) 1997 Elsevier Science S.A.
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