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- Avery, P. J., et al.
(författare)
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A Proposal for an Individualized Pharmacogenetics-Based Warfarin Initiation Dose Regimen for Patients Commencing Anticoagulation Therapy
- 2011
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 90:5, s. 701-706
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Tidskriftsartikel (refereegranskat)abstract
- A significant proportion of the interindividual variability in warfarin dose requirements can be explained on the basis of CYP2C9 and VKORC1 genotypes. We report the development of a novel pharmacogenetics-based 3-day warfarin initiation dose (ID) algorithm based on the International Warfarin Pharmacogenetics Consortium (IWPC) maintenance dose algorithm and the CYP2C9 genotype-based variance in warfarin half-life. The predictive value of the pharmacogenetics-based ID was assessed in a large cohort of 671 newly diagnosed patients with thromboembolic disorders who were about to commence anticoagulation therapy in accordance with standard induction regimens. In patients with mean international normalized ratio (INR)(days 4-7)>4.0 (n = 63) after warfarin initiation, the pharmacogenetics-based ID algorithm predicted a markedly lower dose requirement (median reduction = 4.2 mg), whereas in those with mean INR(days 4-7) < 2.0 (n = 145), the predicted dose requirement was very similar to that in the standard regimen. The use of a pharmacogenetics-based ID may avoid overshooting of INR in warfarin-sensitive patients without unduly affecting the time taken to reach target range in the majority of patients.
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- Danad, Ibrahim, et al.
(författare)
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Carotid artery intima-media thickness, but not coronary artery calcium, predicts coronary vascular resistance in patients evaluated for coronary artery disease
- 2012
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Ingår i: European Heart Journal: Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 13:4, s. 317-323
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Tidskriftsartikel (refereegranskat)abstract
- Aims There is growing evidence that coronary artery disease (CAD) affects not only the conduit epicardial coronary arteries, but also the microvascular coronary bed. Moreover, coronary microvascular dysfunction (CMVD) often precedes the stage of clinically overt epicardial CAD. Coronary artery calcium (CAC) and carotid intima-media thickness (C-IMT) measured with computed tomography (CT) and ultrasound, respectively, are among the available techniques to non-invasively assess atherosclerotic burden. An increased CAC score and C-IMT have also been associated with CMVD. It is therefore of interest to explore and compare the potential of CAC against C-IMT to predict minimal coronary vascular resistance (CVR). Methods and results We evaluated 120 patients (mean age 56 +/- 9 years, 58 men) without a documented history of CAD in whom and results obstructive CAD was excluded. All patients underwent C-IMT measurements, CAC scoring, and vasodilator stress O-15-water positron emission tomography (PET)/CT, during which the coronary flow reserve (CFR) and minimal CVR were analysed. Minimal CVR increased significantly with increasing tertiles of C-IMT (22 +/- 6, 27 +/- 11, and 28 +/- 9 mmHg mL(-1) min(-1) g(-1), P < 0.01), whereas the CFR was comparable across all C-IMT groups (P = 0.50). Minimal CVR increased significantly with an increase in CAC score (23 +/- 9, 27 +/- 8, 32 +/- 10, and 32 +/- 7 mmHg mL(-1) min(-1) g(-1). P < 0.01), whereas the CFR did not show a significant decrease with higher CAC scores (P = 0.18). Multivariable regression analysis revealed that C-IMT (P = 0.03), but not CAC, was independently associated with minimal CVR. Conclusion C-IMT, but not CAC score, independently predicts minimal CVR in patients with multiple cardiovascular risk factors and suspected of CAD.
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- Verhoef, Talitha I, et al.
(författare)
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A systematic review of cost-effectiveness analyses of pharmacogenetic-guided dosing in treatment with coumarin derivatives.
- 2010
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Ingår i: Pharmacogenomics (London). - : Future Medicine Ltd. - 1462-2416 .- 1744-8042. ; 11:7, s. 989-1002
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Tidskriftsartikel (refereegranskat)abstract
- Anticoagulant therapy with coumarin derivatives is often sub- or supra-therapeutic, resulting in an increased risk of thromboembolic events or hemorrhage, respectively. Pharmacogenetic-guided dosing has been proposed as an effective way of reducing bleeding rates. Clinical trials to confirm the safety, efficacy and effectiveness of this strategy are ongoing, but in addition, it is also necessary to consider the cost-effectiveness of this strategy. This article describes the findings of a systematic review of published cost-effectiveness analyses of pharmacogenetic-guided dosing of coumarin derivatives. Similarities and differences in the approaches used were examined and the quality of the analyses was assessed. The results of the analyses are not sufficient to determine whether or not pharmacogenetic-guided dosing of coumarins is cost effective. More reliable cost-effectiveness estimates need to become available before it is possible to recommend whether or not this strategy should be applied in clinical practice.
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- Verhoef, Talitha I, et al.
(författare)
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Cost-effectiveness of pharmacogenetics in anticoagulation: international differences in healthcare systems and costs
- 2012
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Ingår i: Pharmacogenomics (London). - : Future Medicine. - 1462-2416 .- 1744-8042. ; 13:12, s. 1405-1417
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Forskningsöversikt (refereegranskat)abstract
- Genotyping patients for CYP2C9 and VKORC1 polymorphisms can improve the accuracy of dosing during the initiation of anticoagulation with vitamin K antagonists (coumarin derivatives). The anticipated degree of improvement in the safety of anticoagulation with coumarins through genotyping may vary depending on the quality of patient care, which varies both with and among countries. The management and the cost of anticoagulant care can therefore influence the cost effectiveness of genotyping within any given country. In this article, we provide an overview of the cost effectiveness of pharmacogenetics-guided dosing of coumarin derivatives. We describe the organization of anticoagulant care in the UK, Sweden, The Netherlands, Greece, Germany and Austria, where a genotype-guided dosing algorithm is currently being investigated as part of the EU-PACT trial. We also explore the costs of anticoagulant care for the treatment of atrial fibrillation in these countries.
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