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- Diener, Hans-Christoph, et al.
(författare)
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Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial : a double-blind, active and placebo-controlled study.
- 2008
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 7:10, s. 875-884
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.METHODS: Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT00153062.FINDINGS: 20,332 patients (mean age 66 years) were randomised and followed-up for a median of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0.38), or with telmisartan versus placebo (p=0.61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups.INTERPRETATION: Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan.
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| 2. |
- Feuerbacher, Michael, et al.
(författare)
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The Samson phase, β-Mg2Al3, revisited
- 2007
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Ingår i: Zeitschrift fur Kristallographie. - : Walter de Gruyter GmbH. - 0044-2968. ; 222:6, s. 259-288
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Forskningsöversikt (refereegranskat)abstract
- The Al-Mg phase diagram has been reinvestigated in the vicinity of the stability range of the Samson phase, β-Mg2Al3 (cF1168). For the composition Mg38.5Al61.5, this cubic phase, space group Fd3̄m (no 227), a = 28.242(1) Å, V = 22526(2) Å3, undergoes at 214°C a first-order phase transition to rhombohedral β′-Mg2Al3, (hR293), a = 19.968(1) Å, c = 48.9114(8) Å, V = 16889(2) Å3, (i.e. 22519 Å3 for the equivalent cubic unit cell) space group R3m (no 160), a subgroup of index four of Fd3̄m. The structure of the β-phase has been redetermined at ambient temperature as well as in situ at 400°C. It essentially agrees with Samson's model, even in most of the many partially occupied and split positions. The structure of β′-Mg 2Al3 is closely related to that of the β-phase. Its atomic sites can be derived from those of the β-phase by group-theoretical considerations. The main difference between the two structures is that all atomic sites are fully occupied in case of the β′-phase. The reciprocal space, Bragg as well as diffuse scattering, has been explored as function of temperature and the β- to β′-phase transition was studied in detail. The microstructures of both phases have been analyzed by electron microscopy and X-ray topography showing them highly defective. Finally, the thermal expansion coefficients and elastic parameters have been determined. Their values are somewhere in between those of Al and Mg.
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| 5. |
- Weber, Michael A, et al.
(författare)
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A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension : a randomised, double-blind, placebo-controlled trial
- 2009
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 374:9699, s. 1423-1431
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHypertension cannot always be adequately controlled with available drugs. We investigated the blood-pressure-lowering effects of the new vasodilatory, selective endothelin type A antagonist, darusentan, in patients with treatment-resistant hypertension.MethodsThis randomised, double-blind study was undertaken in 117 sites in North and South America, Europe, New Zealand, and Australia. 379 patients with systolic blood pressure of 140 mm Hg or more (≥130 mm Hg if patient had diabetes or chronic kidney disease) who were receiving at least three blood-pressure-lowering drugs, including a diuretic, at full or maximum tolerated doses were randomly assigned to 14 weeks' treatment with placebo (n=132) or darusentan 50 mg (n=81), 100 mg (n=81), or 300 mg (n=85) taken once daily. Randomisation was made centrally via an automated telephone system, and patients and all investigators were masked to treatment assignments. The primary endpoints were changes in sitting systolic and diastolic blood pressures. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00330369.FindingsAll randomly assigned participants were analysed. The mean reductions in clinic systolic and diastolic blood pressures were 9/5 mm Hg (SD 14/8) with placebo, 17/10 mm Hg (15/9) with darusentan 50 mg, 18/10 mm Hg (16/9) with darusentan 100 mg, and 18/11 mm Hg (18/10) with darusentan 300 mg (p<0·0001 for all effects). The main adverse effects were related to fluid accumulation. Oedema or fluid retention occurred in 67 (27%) patients given darusentan compared with 19 (14%) given placebo. One patient in the placebo group died (sudden cardiac death), and five patients in the three darusentan dose groups combined had cardiac-related serious adverse events.InterpretationDarusentan provides additional reduction in blood pressure in patients who have not attained their treatment goals with three or more antihypertensive drugs. As with other vasodilatory drugs, fluid management with effective diuretic therapy might be needed.
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