How to manage warfarin therapy.
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ABSTRACT:
SUBMITTER: Tideman PA
PROVIDER: S-EPMC4653986 | biostudies-literature | 2015 Apr
REPOSITORIES: biostudies-literature
Publications
How to manage warfarin therapy.
Tideman Philip A PA Tirimacco Rosy R St John Andrew A Roberts Gregory W GW
Australian prescriber 20150401 2
Long-term treatment with warfarin is recommended for patients with atrial fibrillation at risk of stroke and those with recurrent venous thrombosis or prosthetic heart valves. Patient education before commencing warfarin - regarding signs and symptoms of bleeding, the impact of diet, potential drug interactions and the actions to take if a dose is missed - is pivotal to successful use. Scoring systems such as the CHADS2 score are used to determine if patients with atrial fibrillation are suitabl ...[more]
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| S-EPMC10287501 | biostudies-literature
Project description:Warfarin is the most widely used oral anticoagulant in clinical practice. The cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex 1 (VKORC1), and cytochrome P450 4F2 (CYP4F2) genotypes are associated with warfarin dose requirements in China. Accurate genotyping is vital for obtaining reliable genotype-guided warfarin dosing information. The current method for individualized dosing gene polymorphism detection for warfarin has the disadvantages of being easily contaminated, time-consuming, expensive, and unsuitable for clinical use. Herein, we present a novel application, a multiplex fluorescent melting curve assay of whole-blood direct amplification of nested polymerase chain reaction (PCR), to genotyping single-nucleotide polymorphism (SNPs) rapidly that affect warfarin efficacy. This method requires only 1 µL of whole blood, no DNA extraction, takes less than 2 h, costs less than $1, and is able to accurately distinguish between different SNP sites. Polymorphic loci were detected in whole blood specimens of 181 clinical warfarin-administered patients through nested blood direct PCR fluorescence melting curve analysis and gene sequencing. The results of the nested blood direct PCR multiplex fluorescence melting curve technology were 100% consistent with those of sequencing-characterized by high accuracy and high specificity. The allele frequencies were 94.5% for A and 5.5% for C at CYP2C9*3 (rs1057910), 7.5% for G and 92.5% for A at VKORC1 (rs9923231), and 77.1% for G and 22.9% for A at CYP4F2*3 (rs2108622). For CYP2C9*2 (rs1799853), only allele C was detected, with a frequency of 100%. Warfarin doses were lower in the CYP2C9*1*1 genotype population than in the CYP2C9*1*3 population, lower in the VKORC1 (AA) population than in the VKORC1 (GG) population, and higher in individuals with the CYP4F2*3 mutation (GA/AA) compared with those with wild-type (GG). In summary, the detection and genotyping of four polymorphic SNP sites using a multiplex fluorescent melting curve assay of whole blood direct amplification through nested PCR is highly importance for guiding personalized warfarin anticoagulant therapy.
| S-EPMC11686395 | biostudies-literature
Project description:pilot project for the co-creation of genomics-informed best management practices for timber conservation and extraction under global change in French Guiana
| PRJEB83334 | ENA
Project description:Most patients receiving warfarin are managed in outpatient office settings or anticoagulation clinics that require frequent visits for monitoring.To measure the amount and value of time required of patients for chronic anticoagulation therapy with warfarin./Participants. Prospective observation of a cohort of adult patients treated at a university-based anticoagulation program. Measurements. Participants completed a questionnaire and a prospective diary of the time required for 1 visit to the anticoagulation clinic, including travel, waiting, and the clinic visit. The authors reviewed subjects' medical records to obtain additional information, including the frequency of visits to the anticoagulation clinic. They used the human capital method to estimate the value of time.Eighty-five subjects completed the study. The mean (median) total time per visit was 147 minutes (123). Subjects averaged 15 visits per year (14) and spent 39.0 hours (29.3) per year on their visits. Other anticoagulation-related activities, such as communication with providers, pharmacy trips, and extra time preparing food, added an average of 52.7 hours (19.0) per year. The mean annual value of patient time spent traveling, waiting, and attending anticoagulation visits was $707 (median $591). The mean annual value when also including other anticoagulation-related activities was $1799 (median $1132).The time required of patients for anticoagulation visits was considerable, averaging approximately 2.5 hours per visit and almost 40 hours per year.for reducing patient time requirements, such as home-based testing, could reduce costs for patients, employers, and companions.
| S-EPMC4181607 | biostudies-literature
Project description:BackgroundAlthough warfarin has been extensively studied in clinical trials, little is known about rates of hemorrhage attributable to its use in routine clinical practice. Our objective was to examine incident hemorrhagic events in a large population-based cohort of patients with atrial fibrillation who were starting treatment with warfarin.MethodsWe conducted a population-based cohort study involving residents of Ontario (age ≥ 66 yr) with atrial fibrillation who started taking warfarin between Apr. 1, 1997, and Mar. 31, 2008. We defined a major hemorrhage as any visit to hospital for hemorrage. We determined crude rates of hemorrhage during warfarin treatment, overall and stratified by CHADS(2) score (congestive heart failure, hypertension, age ≥ 75 yr, diabetes mellitus and prior stroke, transient ischemic attack or thromboembolism).ResultsWe included 125 195 patients with atrial fibrillation who started treatment with warfarin during the study period. Overall, the rate of hemorrhage was 3.8% (95% confidence interval [CI] 3.8%-3.9%) per person-year. The risk of major hemorrhage was highest during the first 30 days of treatment. During this period, rates of hemorrhage were 11.8% (95% CI 11.1%-12.5%) per person-year in all patients and 16.7% (95% CI 14.3%-19.4%) per person-year among patients with a CHADS(2) scores of 4 or greater. Over the 5-year follow-up, 10 840 patients (8.7%) visited the hospital for hemorrhage; of these patients, 1963 (18.1%) died in hospital or within 7 days of being discharged.InterpretationIn this large cohort of older patients with atrial fibrillation, we found that rates of hemorrhage are highest within the first 30 days of warfarin therapy. These rates are considerably higher than the rates of 1%-3% reported in randomized controlled trials of warfarin therapy. Our study provides timely estimates of warfarin-related adverse events that may be useful to clinicians, patients and policy-makers as new options for treatment become available.
| S-EPMC3563912 | biostudies-literature
Project description:High variability in drug response and a narrow therapeutic index complicate warfarin therapy initiation. No existing algorithm provides recommendations on refining the initial warfarin dose based on genetic variables, clinical data, and international normalized ratio (INR) values. Our goal was to develop such an algorithm. We studied 92 patients undergoing primary or revision total hip or knee replacement. From each patient we collected a blood sample, clinical variables, current medications, and preoperative and postoperative laboratory values. We genotyped for polymorphisms in the cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase (VKORC1) genes. Using stepwise regression, we developed a model for refining the warfarin dose after the third warfarin dose. The algorithm explained four fifths of the variability in therapeutic dose (R(2)(adj) of 79%). Significant (P > .05) predictors were INR value after 3 doses (47% reduction per 0.25-unit rise), first warfarin dose (+7% per 1 mg), CYP2C9*3 and CYP2C9*2 genotype (-38% and -17% per allele), estimated blood loss (interacting with INR(3)), smoking status (+20% in current smokers), and VKORC1 (-11% per copy of haplotype A). If validated, this model should provide a safer, more effective process for initiating warfarin therapy.
| S-EPMC1975838 | biostudies-literature
Project description:BACKGROUND:A combination of warfarin, aspirin and clopidogrel is indicated after percutaneous coronary intervention (PCI) in some patients, despite the higher risk of bleeding inferred by this triple therapy. OBJECTIVES:Whether the treatment quality of warfarin measured by iTTR (individual time within therapeutic INR range) is associated with bleeding complications during triple therapy after PCI. METHODS:A retrospective register study consisting of 601 triple treated PCI patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). The cohort was cross-matched with the Swedish Patient Registry for background characteristics and bleeding complications up to 6 months after PCI using ICD10 codes, the Prescribed Drug Registry for ongoing medications, and the national oral anticoagulation registry Auricula for warfarin treatment quality. The patients were grouped into four iTTR groups: <50%, 50-69.9%, 70-84.9% and >85% as well as iTTR above or below 70%. RESULTS:Of 601 patients, 39 (6.5%) had a bleeding complication (type 2 according to BARC). Bleeding was more common for iTTR<70% compared to iTTR>70%, 28 (9.3%) vs. 11 (3.7%) (p = 0.005). The bleeding frequency increased gradually from the best group, iTTR>85% with four bleeders (3.3%) up to 17 bleeders (13.3%) in the worst group with iTTR<50% (p = 0.003), with a corresponding bleeding rate per 100 treatment years of 8.0 and 44.9, respectively. In multivariate analysis low BMI, HR 1.11 (95% CI 1.01-1.22), a medical history of anemia HR 3.17 (1.16-8.69) and iTTR < 70% HR 2.86 (1.25-6.53) increased the risk of bleeding. CONCLUSION:Triple therapy after PCI confers a high risk of bleeding events. Warfarin treatment quality measured by iTTR as well as a medical history of anemia are strong independent predictors of bleeding in these patients. Physicians should pay more attention to iTTR after PCI.
| S-EPMC6298652 | biostudies-literature
Project description:Background and aimWarfarin is the most frequently prescribed anticoagulant worldwide. However, warfarin therapy is associated with a high risk of bleeding and thromboembolic events because of a large interindividual dose-response variability. We investigated the effect of genetic and non genetic factors on warfarin dosage in a South Italian population in the attempt to setup an algorithm easily applicable in the clinical practice.Materials and methodsA total of 266 patients from Southern Italy affected by cardiovascular diseases were enrolled and their clinical and anamnestic data recorded. All patients were genotyped for CYP2C9 2, 3, CYP4F2 3, VKORC1 -1639 G>A by the TaqMan assay and for variants VKORC1 1173 C>T and VKORC1 3730 G>A by denaturing high performance liquid chromatography and direct sequencing. The effect of genetic and not genetic factors on warfarin dose variability was tested by multiple linear regression analysis, and an algorithm based on our data was established and then validated by the Jackknife procedure.ResultsWarfarin dose variability was influenced, in decreasing order, by VKORC1-1639 G>A (29.7%), CYP2C9 3 (11.8%), age (8.5%), CYP2C9 2 (3.5%), gender (2.0%) and lastly CYP4F2 3 (1.7%); VKORC1 1173 C>T and VKORC1 3730 G>A exerted a slight effect (<1% each). Taken together, these factors accounted for 58.4% of the warfarin dose variability in our population. Data obtained with our algorithm significantly correlated with those predicted by the two online algorithms: Warfarin dosing and Pharmgkb (p<0.001; R(2)?=?0.805 and p<0.001; R(2)?=?0.773, respectively).ConclusionsOur algorithm, which is based on six polymorphisms, age and gender, is user-friendly and its application in clinical practice could improve the personalized management of patients undergoing warfarin therapy.
| S-EPMC3753327 | biostudies-literature
Project description:BackgroundStroke prevention by warfarin, a vitamin K antagonist, has been an integral part in the management of atrial fibrillation. Vitamin K-dependent matrix Gla protein (MGP) has been known as a potent inhibitor of arterial calcification and osteoporosis. Therefore, we hypothesized that warfarin therapy affects bone mineral metabolism, vascular calcification, and vascular endothelial dysfunction.MethodsWe studied 42 atrial fibrillation patients at high-risk for atherosclerosis having one or more coronary risk factors. Twenty-four patients had been treated with warfarin for at least 12 months (WF group), and 18 patients without warfarin (non-WF group). Bone alkaline phosphatase (BAP) and under carboxylated osteocalcin (ucOC) and receptor activator of nuclear factor-kappa B ligand (RANKL) were measured as bone metabolism markers. Reactive hyperemia-peripheral arterial tonometry (RH-PAT) index measured by Endo-PAT2000 was used as an indicator of vascular endothelial function.ResultsThere were no significant differences in patient background characteristics and other clinical indicators between the two groups. In WF group, the ucOC levels were significantly higher than those in the non-WF group (10.3 ± 0.8 vs. 3.4 ± 0.9 ng/mL; P < 0.01), similarly, the RANKL levels in the WF group were higher than those in the non-WF group (0.60 ± 0.06 vs. 0.37 ± 0.05 ng/mL; P = 0.007). Moreover, RH-PAT index was significantly lower in the WF group compared to those in the non-WF group (1.48 ± 0.11 vs. 1.88 ± 0.12; P = 0.017).ConclusionsLong-term warfarin therapy may be associated with bone mineral loss and vascular calcification in 60-80 year old hypertensive patients.
| S-EPMC4661704 | biostudies-literature
Project description:ObjectiveHealth literacy has been related to health-related conditions and health outcomes. Studies examining the association of health literacy and anticoagulation have had variable results. We sought to investigate the relations of health literacy and percentage of time in therapeutic range (TTR) in a vulnerable Brazilian cohort at two hospital-based anticoagulation clinics.MethodsWe measured health literacy with the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA-18) in 2015-2016. We identified the demographic and clinical characteristics associated with health literacy and related health literacy to TTR.ResultsWe enrolled 422 adults prescribed chronic warfarin therapy in our observational study (median age 62.1 years; 58.8% women; monthly income $200.00). The prevalence of inadequate health literacy (score 0-14 points) was 72.3% with a median score of 12 (quartiles, Q1=10; Q3=15) on the SAHLPA-18. The median TTR was 66.1%. In the multivariable logistic analysis, cognitive impairment and assistance with taking warfarin were associated with inadequate health literacy. Prosthetic heart valves and more school years were associated with adequate health literacy. Our analyses showed no significant relation between health literacy and TTR, analysing health literacy as a categorical (adjusted OR 1.05; 95% CI 0.65 to 1.70) or continuous variable (Spearman's coefficient 0.02; p=0.70).ConclusionsInadequate health literacy was highly prevalent in this impoverished Brazilian cohort receiving anticoagulation with warfarin. However, we did not identify an association between health literacy and TTR. Future investigations may consider the systemic factors that contribute towards successful anticoagulation outcomes for vulnerable patient cohorts with inadequate health literacy.
| S-EPMC5595143 | biostudies-literature