Comparison of an age adjusted warfarin loading protocol with empirical dosing and Fennerty's protocol

Roberts, G. W.; Druskeit, Tina; Jorgensen, Lisbeth E; Wing, Lindon; Gallus, Alexander; Miller, Claire Kane; Cosh, David G; Eaton, Vaughn

doi:10.1111/j.1445-5994.1999.tb01623.x

Cited by 55 publications

(47 citation statements)

References 17 publications

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“…In addition, some studies recommend that loading dose should be age adjusted because of concern about warfarin sensitivity. 34 However, we did not observe a disproportional number of elderly patients with excessive anticoagulation with our loading dose regimen, in which some elderly patients were indeed loaded with 10 mg as per genotype. Thus, the present data do not support age-modified loading doses.…”

Section: Discussionmentioning

confidence: 96%

“…1,[34][35][36] Although several of these studies have incorporated loading dose nomograms during initiation, most have been in the setting of VTE, 19,20 and few studies incorporating loading dose strategies for other indications have been reported. 34,37 Pharmacogenomic studies conducted in the last decade have established the contribution of both VKORC1 and CYP2C9 genetic variations to maintenance dose requirements; however, VKORC1 is a more important modulator of early warfarin response than CYP2C9. 24 Not surprisingly, both genes have recently been reported to predict therapeutic doses during the initial weeks of therapy.…”

Section: Discussionmentioning

confidence: 99%

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Prospective evaluation of a pharmacogenetics-guided warfarin loading and maintenance dose regimen for initiation of therapy

Gong

Tirona

Schwarz

et al. 2011

Blood

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Single-nucleotide polymorphisms in genes that affect warfarin metabolism (cytochrome P450 2C9 gene, CYP2C9) and response (vitamin K epoxide reductase complex 1 gene, VKORC1) have an important influence on warfarin therapy, particularly during initiation; however, there is a lack of consensus regarding the optimal pharmacogenetics-based initiation strategy. We conducted a prospective cohort study in which patients requiring warfarin therapy for atrial fibrillation or venous thromboembolism were initiated with a novel pharmacogenetics-initiation protocol (WRAPID, Warfarin Regimen using A Pharmacogenetics-guided Initiation Dosing) that incorporated loading and maintenance doses based on genetics, clinical variables, and response (n ‫؍‬ 167, followed up for 90 days), to assess the influence of genetic variations on anticoagulation responses. Application of the WRAPID algorithm resulted in a negligible influence of genetic variation in VKORC1 or CYP2C9 on time to achievement of first therapeutic response (P ‫؍‬ .52, P ‫؍‬ .28) and risk of overanticoagulation (P ‫؍‬ .64, P ‫؍‬ .96). After adjustment for covariates, time to stable anticoagulation was not influenced by VKORC1 or CYP2C9 genotype. Importantly, time spent within or above the therapeutic range did not differ among VKORC1 and CYP2C9 genotype groups. Moreover, the overall time course of the anticoagulation response among the genotype groups was similar and predictable. We demonstrate the clinical utility of geneticsguided warfarin initiation with the WRAPID protocol to provide safe and optimal anticoagulation therapy for patients with atrial fibrillation or venous thromboembolism. (Blood. 2011;118(11):3163-3171)

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Prospective evaluation of a pharmacogenetics-guided warfarin loading and maintenance dose regimen for initiation of therapy

Gong

Tirona

Schwarz

et al. 2011

Blood

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“…In an attempt to decrease the toxicity of warfarin induction, several dosing algorithms have been proposed, [14][15][16][17][18][19] but none has been widely accepted. A major barrier to their implementation is that most were developed for middleaged inpatients who could tolerate doses of 5-10 mg warfarin daily and who had daily monitoring of the international normalized ratio (INR).…”

Section: Current Approaches To Warfarin Induction Fail To Prevent Advmentioning

confidence: 99%

“…11,20,21 Because warfarin dose requirements decrease with advancing age, 22 use of existing algorithms tends to overdose this growing population. [16][17][18][19] Another problem is that the risk of overdose is increased now that most patients begin warfarin in the outpatient setting, where daily INR monitoring is not feasible (except with patient self-monitoring). The major flaw of existing warfarin algorithms is that they are empiric: they rely on trial-and-error dosing after an initial warfarin dose of 2 to 10 mg, rather than being tailored to individual genetic and clinical factors.…”

Section: Current Approaches To Warfarin Induction Fail To Prevent Advmentioning

confidence: 99%

Pharmacogenetics-Based Coumarin Therapy

Gage¹

2006

Hematology

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To reduce the risk of hemorrhage, experts advocate prescribing the anticipated therapeutic dose to patients who are beginning coumarin therapy, but until now there was no accurate way to estimate that dose. Using pharmacogenetics-based coumarin therapy, clinicians can now estimate the therapeutic dose by genotyping their patients for single nucleotide polymorphisms (SNPs) that affect coumarin metabolism or sensitivity. SNPs in the cytochrome P450 complex (CYP2C9) affect coumarin metabolism. Patients with either of two common variants, CYP2C9*2 or CYP2C9*3, metabolize coumarins slowly and are twice as likely to have a laboratory or clinical adverse event, unless their initial coumarin doses are reduced. SNPs in vitamin K epoxide reductase (VKORC1) correlate with coumarin sensitivity. Patients known to be homozygous for a common VKORC1 promoter polymorphism, −1639 G>A (also designated as VKOR 3673, haplotype A, or haplotype*2), should be started on lower coumarin doses than genotype GG patients. By providing an estimate of the therapeutic coumarin dose, pharmacogenetics-based therapy may improve the safety and effectiveness of coumarin therapy.

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“…Earlier efforts to develop warfarin dosing algorithms have included serial INR measurements in the first days of warfarin use to predict subsequent doses [78,79] and/or limited clinical data (such as sex only) [80]. Such approaches have not been well validated, and are not widely used [40,78,79,81]. One reason for this is that these algorithms do not incorporate other patient, environmental, or genetic factors that alter warfarin dose requirement.…”

Section: Conceptual Framework and Past Experiencementioning

confidence: 99%

Warfarin therapy: in need of improvement after all these years

Kimmel

2008

Expert Opinion on Pharmacotherapy

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Background-Warfarin therapy has been used clinically for over 60 years, yet continues to be problematic because of its narrow therapeutic index and large inter-individual variability in patient response. As a result, warfarin is a leading cause of serious medication-related adverse events, and its efficacy is also suboptimal.Objective-To review factors that are responsible for variable response to warfarin, including clinical, environmental, and genetic factors, and to explore some possible approaches to improving warfarin therapy.Results-Recent efforts have focused on developing dosing algorithms that included genetic information to try to improve warfarin dosing. These dosing algorithms hold promise, but have not been fully validated or tested in rigorous clinical trials. Perhaps equally importantly, adherence to warfarin is a major problem that should be addressed with innovative and cost-effective interventions.Conclusion-Additional research is needed to further test whether interventions can be used to improve warfarin dosing and outcomes.

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Comparison of an age adjusted warfarin loading protocol with empirical dosing and Fennerty's protocol

Cited by 55 publications

References 17 publications

Prospective evaluation of a pharmacogenetics-guided warfarin loading and maintenance dose regimen for initiation of therapy

Prospective evaluation of a pharmacogenetics-guided warfarin loading and maintenance dose regimen for initiation of therapy

Pharmacogenetics-Based Coumarin Therapy

Warfarin therapy: in need of improvement after all these years

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