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- Baruch, Lawrence, et al.
(författare)
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Can patients at elevated risk of stroke treated with anticoagulants be further risk stratified?
- 2007
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 38:9, s. 2459-2463
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose - Patients with atrial fibrillation have a varied risk of stroke, depending on age and comorbid conditions. The objective of this study was to assess the predictive value of stroke risk classification schemes and to identify patients with atrial fibrillation who are at substantial risk of stroke despite optimal anticoagulant therapy. Methods - Seven recognized classification schemes - the American College of Chest Physicians 2001, American College of Chest Physicians 2004, Stroke Prevention in Atrial Fibrillation (SPAF), Atrial Fibrillation Investigators, Framingham, van Walraven, and CHADS(2) - were compared for their ability to predict ischemic stroke in patients receiving anticoagulant therapy. Data came from the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation III and V trials, which compared the efficacy of adjusted-dose warfarin and the direct thrombin inhibitor ximelagatran (36 mg twice daily) in preventing thromboembolic events in 7329 patients with chronic or paroxysmal nonvalvular atrial fibrillation who were at moderate or high risk of ischemic stroke. The main outcome measure was ischemic stroke, as determined by a central event adjudication committee. Results - During 11 245 patient-years of follow-up, 159 patients had an ischemic stroke (1.4%/year). As indicated by c statistics and hazard ratios, 3 of the classification schemes predicted stroke significantly better than chance: Framingham (c = 0.64), CHADS2 (c = 0.65), and SPAF (c = 0.61). Conclusions - In a large cohort of atrial fibrillation patients at moderate or high risk of ischemic stroke treated with warfarin or ximelagatran, the CHADS2, SPAF, and Framingham schemes had greater predictive accuracy than chance. This predictive ability may allow clinicians to target high-risk patients for more aggressive intervention.
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| 2. |
- Limdi, Nita A., et al.
(författare)
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Warfarin pharmacogenetics : a single VKORC1 polymorphism is predictive of dose across three racial groups
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:18, s. 3827-3834
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Tidskriftsartikel (refereegranskat)abstract
- Warfarin dosing algorithms incorporating CYP2C9 and VKORC1-1639G>A improve dose prediction compared to algorithms based solely on clinical and demographic factors. However these algorithms better capture dose variability among Whites compared to Asians or Blacks. Herein we evaluate whether other VKORC1 polymorphisms and haplotypes explain additional variation in warfarin dose beyond that explained by VKORC1-1639G>A among Asians (n=1103), Blacks (n=670) and Whites (n=3113). Participants were recruited from 11 countries as part of the International Warfarin Pharmacogenetics Consortium effort. Evaluation of the effects of individual VKORC1 SNPs and haplotypes on warfarin dose employed both univariate and multivariable linear regression. VKORC1-1639G>A and 1173C>T individually explained the greatest variance in dose in all three racial groups. Incorporation of additional VKORC1 SNPs or haplotypes did not further improve dose prediction. VKORC1 explained greater variability in dose among Whites as compared to Blacks and Asians. Differences in the percent variance in dose explained by VKORC1 across race was largely accounted for by the frequency of the -1639 A (or 1173 T) allele. Thus, clinicians should recognize that although at a population level, the contribution of VKORC1 towards dose requirements is higher in Whites compared to non-whites; genotype predicts similar dose requirements across racial groups.
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