| 1. |
- Diener, Hans-Christoph, et al.
(författare)
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Stroke prevention using the oral direct thrombin inhibitor ximelagatran inpatients with nonvalvular atrial fibrillation. Pooled analysis from the SPORTIF III ad V studies.
- 2006
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 21:4, s. 279-293
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Tidskriftsartikel (refereegranskat)abstract
- Background: To show results of a prespecified pooled analysis of the studies SPORTIF III (open-label) and SPORTIF V (double-blind), to assess the homogeneity of the results and to explore subgroup analyses and adverse events. Methods and Results: 7,329 patients with atrial fibrillation (AF) and 1 additional stroke risk factor were randomized to warfarin (international normalized ratio 2.0-3.0) or ximelagatran (36 mg twice daily). Over 11,346 patient-years (mean 18.5 months/patient), 184 patients developed primary events of stroke and systemic embolism (ximelagatran 1.62 vs. warfarin 1.65%/year; p = 0.94). Heterogeneity between trials with respect to the primary event rate (study-by-treatment interaction p = 0.026) was found. This could not be explained statistically by baseline patient characteristics or by treatment (except perhaps by the better anticoagulation with warfarin in SPORTIF V) and was not evident for secondary end-points. There was no conclusive difference in major bleeding rates (ximelagatran 1.88 vs. warfarin 2.46%/year; p = 0.054), but combined minor plus major bleeding was lower with ximelagatran (31.7 vs. 38.7%/year; p < 0.0001). Elevation of liver enzymes occurred more frequently in patients taking ximelagatran (6.1% vs. warfarin 0.8%; p < 0.0001) and was reversible except in rare cases. Conclusions: Fixed-dose oral ximelagatran without coagulation monitoring prevented stroke and systemic embolism as effectively as warfarin in patients with AF. Differences in the results of the two trials might relate to consistency of warfarin anticoagulation, different degree of blinding in the two trials, other concomitant therapies or chance. Further investigation is required to explore the long-term safety profile of ximelagatran.
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| 2. |
- Kirchhof, Paulus, et al.
(författare)
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Outcome parameters for trials in atrial fibrillation: executive summary
- 2007
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 28:22, s. 2803-2817
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Forskningsöversikt (refereegranskat)abstract
- Atrial fibrillation (AF), the most common atrial arrhythmia, has a complex aetiology and causes relevant morbidity and mortality due to different mechanisms, including but not limited to stroke, heart failure, and tachy- or bradyarrhythmia. Current therapeutic options (rate control, rhythm control, antithrombotic therapy, 'upstream therapy') only prevent a part of this burden of disease. Several new treatment modalities are therefore under evaluation in controlled trials. Given the multifold clinical consequences of AF, trials in AF patients should assess the effect of therapy in each of the main outcome domains. This paper describes an expert consensus of required outcome parameters in seven relevant outcome domains, namely death, stroke, symptoms and quality of life, rhythm, left ventricular function, cost, and emerging outcome parameters. In addition to these 'requirements' for outcome assessment in AF trials, further, more detailed outcome parameters are described. In addition to a careful selection of a relevant primary outcome parameter, coverage of outcomes in all major domains of AF- related morbidity and mortality is desirable for any clinical trial in AF.
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| 3. |
- Kirchhof, Paulus, et al.
(författare)
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Outcome parameters for trials in atrial fibrillation - Recommendations from a consensus conference organized by the German atrial fibrillation competence NETwork and the European Heart Rhythm Association
- 2007
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Ingår i: Europace. - : Oxford University Press (OUP). - 1532-2092 .- 1099-5129. ; 9:11, s. 1006-1023
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Forskningsöversikt (refereegranskat)abstract
- Atrial fibrillation (AF), the most common atria[ arrhythmia, has a complex aetiology and causes relevant morbidity and mortality due to different mechanisms, including but not limited to stroke, heart failure, and tachy- or bradyarrhythmia. Current therapeutic options (rate control, rhythm control, antithrombotic therapy, 'upstream therapy') only prevent a part of this burden of disease. New treatment modalities are therefore currently under evaluation in clinical trials. Given the multifold clinical consequences of AF, controlled trials in AF patients should assess the effect of therapy in each of the main outcome domains. This paper describes an expert consensus of required outcome parameters in seven relevant outcome domains, namely death, stroke, symptoms and quality of life, rhythm, left ventricular function, cost, and emerging outcome parameters. In addition to these 'requirements' for outcome assessment in AF trials, further outcome parameters are described in each outcome domain. In addition to a careful selection of a relevant primary outcome parameter, coverage of outcomes in all major domains of AF-related morbidity and mortality is desirable for any clinical trial in AF.
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