Publications (53)353.03 Total impact
-
Article: The analysis of bleeding risk-prediction scores should include all major bleeds.
Journal of the American College of Cardiology 01/2013; 61(4):481-2. · 14.16 Impact Factor -
Article: Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation.
[show abstract] [hide abstract]
ABSTRACT: Recent studies have investigated alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation (AF), but whether these alternatives are cost-effective is unknown. On the basis of the results from Randomized Evaluation of Long Term Anticoagulation Therapy (RE-LY) and other trials, we developed a decision-analysis model to compare the cost and quality-adjusted survival of various antithrombotic therapies. We ran our Markov model in a hypothetical cohort of 70-year-old patients with AF using a cost-effectiveness threshold of $50 000/quality-adjusted life-year. We estimated the cost of dabigatran as US $9 a day. For a patient with an average risk of major hemorrhage (≈3%/y), the most cost-effective therapy depended on stroke risk. For patients with the lowest stroke rate (CHADS2 stroke score of 0), only aspirin was cost-effective. For patients with a moderate stroke rate (CHADS2 score of 1 or 2), warfarin was cost-effective unless the risk of hemorrhage was high or quality of international normalized ratio control was poor (time in the therapeutic range <57.1%). For patients with a high stroke risk (CHADS(2) stroke score ≥3), dabigatran 150 mg (twice daily) was cost-effective unless international normalized ratio control was excellent (time in the therapeutic range >72.6%). Neither dabigatran 110 mg nor dual therapy (aspirin and clopidogrel) was cost-effective. Dabigatran 150 mg (twice daily) was cost-effective in AF populations at high risk of hemorrhage or high risk of stroke unless international normalized ratio control with warfarin was excellent. Warfarin was cost-effective in moderate-risk AF populations unless international normalized ratio control was poor.Circulation 06/2011; 123(22):2562-70. · 14.74 Impact Factor -
Article: Genetic warfarin dosing: tables versus algorithms.
[show abstract] [hide abstract]
ABSTRACT: The aim of this study was to compare the accuracy of genetic tables and formal pharmacogenetic algorithms for warfarin dosing. Pharmacogenetic algorithms based on regression equations can predict warfarin dose, but they require detailed mathematical calculations. A simpler alternative, recently added to the warfarin label by the U.S. Food and Drug Administration, is to use genotype-stratified tables to estimate warfarin dose. This table may potentially increase the use of pharmacogenetic warfarin dosing in clinical practice; however, its accuracy has not been quantified. A retrospective cohort study of 1,378 patients from 3 anticoagulation centers was conducted. Inclusion criteria were stable therapeutic warfarin dose and complete genetic and clinical data. Five dose prediction methods were compared: 2 methods using only clinical information (empiric 5 mg/day dosing and a formal clinical algorithm), 2 genetic tables (the new warfarin label table and a table based on mean dose stratified by genotype), and 1 formal pharmacogenetic algorithm, using both clinical and genetic information. For each method, the proportion of patients whose predicted doses were within 20% of their actual therapeutic doses was determined. Dosing methods were compared using McNemar's chi-square test. Warfarin dose prediction was significantly more accurate (all p < 0.001) with the pharmacogenetic algorithm (52%) than with all other methods: empiric dosing (37%; odds ratio [OR]: 2.2), clinical algorithm (39%; OR: 2.2), warfarin label (43%; OR: 1.8), and genotype mean dose table (44%; OR: 1.9). Although genetic tables predicted warfarin dose better than empiric dosing, formal pharmacogenetic algorithms were the most accurate.Journal of the American College of Cardiology 02/2011; 57(5):612-8. · 14.16 Impact Factor -
Article: Cost of dabigatran for atrial fibrillation.
BMJ (Clinical research ed.). 01/2011; 343:d6980. -
Article: Statistical design of personalized medicine interventions: the Clarification of Optimal Anticoagulation through Genetics (COAG) trial.
[show abstract] [hide abstract]
ABSTRACT: There is currently much interest in pharmacogenetics: determining variation in genes that regulate drug effects, with a particular emphasis on improving drug safety and efficacy. The ability to determine such variation motivates the application of personalized drug therapies that utilize a patient's genetic makeup to determine a safe and effective drug at the correct dose. To ascertain whether a genotype-guided drug therapy improves patient care, a personalized medicine intervention may be evaluated within the framework of a randomized controlled trial. The statistical design of this type of personalized medicine intervention requires special considerations: the distribution of relevant allelic variants in the study population; and whether the pharmacogenetic intervention is equally effective across subpopulations defined by allelic variants. The statistical design of the Clarification of Optimal Anticoagulation through Genetics (COAG) trial serves as an illustrative example of a personalized medicine intervention that uses each subject's genotype information. The COAG trial is a multicenter, double blind, randomized clinical trial that will compare two approaches to initiation of warfarin therapy: genotype-guided dosing, the initiation of warfarin therapy based on algorithms using clinical information and genotypes for polymorphisms in CYP2C9 and VKORC1; and clinical-guided dosing, the initiation of warfarin therapy based on algorithms using only clinical information. We determine an absolute minimum detectable difference of 5.49% based on an assumed 60% population prevalence of zero or multiple genetic variants in either CYP2C9 or VKORC1 and an assumed 15% relative effectiveness of genotype-guided warfarin initiation for those with zero or multiple genetic variants. Thus we calculate a sample size of 1238 to achieve a power level of 80% for the primary outcome. We show that reasonable departures from these assumptions may decrease statistical power to 65%. In a personalized medicine intervention, the minimum detectable difference used in sample size calculations is not a known quantity, but rather an unknown quantity that depends on the genetic makeup of the subjects enrolled. Given the possible sensitivity of sample size and power calculations to these key assumptions, we recommend that they be monitored during the conduct of a personalized medicine intervention. clinicaltrials.gov: NCT00839657.Trials 11/2010; 11:108. · 2.02 Impact Factor -
Article: Gamma-glutamyl carboxylase and its influence on warfarin dose.
[show abstract] [hide abstract]
ABSTRACT: Via generation of vitamin K-dependent proteins, gamma-glutamyl carboxylase (GGCX) plays a critical role in the vitamin K cycle. Single nucleotide polymorphisms (SNPs) in GGCX, therefore, may affect dosing of the vitamin K antagonist, warfarin. In a multi-centered, cross-sectional study of 985 patients prescribed warfarin therapy, we genotyped for two GGCX SNPs (rs11676382 and rs12714145) and quantified their relationship to therapeutic dose. GGCX rs11676382 was a significant (p=0.03) predictor of residual dosing error and was associated with a 6.1% reduction in warfarin dose (95% CI: 0.6%-11.4%) per G allele. The prevalence was 14.1% in our predominantly (78%) Caucasian cohort, but the overall contribution to dosing accuracy was modest (partial R2 = 0.2%). GGCX rs12714145 was not a significant predictor of therapeutic dose (p = 0.26). GGCX rs11676382 is a statistically significant predictor of warfarin dose, but the clinical relevance is modest. Given the potentially low marginal cost of adding this SNP to existing genotyping platforms, we have modified our non-profit website (www.WarfarinDosing.org) to accommodate knowledge of this variant.Thrombosis and Haemostasis 10/2010; 104(4):750-4. · 5.04 Impact Factor -
Article: Cost-effectiveness of outpatient cardiac monitoring to detect atrial fibrillation after ischemic stroke.
[show abstract] [hide abstract]
ABSTRACT: Extending the duration of continuous electrocardiography after ischemic stroke detects more new cases of atrial fibrillation, which is an important and treatable cause of stroke, but the cost-effectiveness of this approach is unknown. Therefore, we performed a cost-utility analysis of outpatient cardiac monitoring after ischemic stroke. Using a Markov model, we determined the lifetime cost and utility of warfarin therapy in a hypothetical cohort of 70-year-old patients with atrial fibrillation, prior stroke, and no contraindication to warfarin therapy. Meta-analysis was used to determine the yield of outpatient cardiac monitoring. Outpatient cardiac monitoring would detect 44 new cases of atrial fibrillation for every 1000 patients monitored. This would result in a gain of 34 quality-adjusted life-years at a net cost of $440,000. Therefore, the cost-utility ratio of outpatient cardiac monitoring would be $13,000 per quality-adjusted life-years gained. Outpatient monitoring remained cost-effective throughout a wide range of model inputs in sensitivity analyses, including changes in the cost and yield of monitoring. By identifying patients with paroxysmal atrial fibrillation who will benefit from anticoagulation, outpatient cardiac monitoring is cost-effective after ischemic stroke over a wide range of model inputs. The optimal duration and method of monitoring is unknown.Stroke 07/2010; 41(7):1514-20. · 5.73 Impact Factor -
Article: Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups.
[show abstract] [hide abstract]
ABSTRACT: Warfarin-dosing algorithms incorporating CYP2C9 and VKORC1 -1639G>A improve dose prediction compared with algorithms based solely on clinical and demographic factors. However, these algorithms better capture dose variability among whites than 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 single nucleotide polymorphisms (SNPs) and haplotypes on warfarin dose used both univariate and multi variable linear regression. VKORC1 -1639G>A and 1173C>T individually explained the greatest variance in dose in all 3 racial groups. Incorporation of additional VKORC1 SNPs or haplotypes did not further improve dose prediction. VKORC1 explained greater variability in dose among whites than blacks and Asians. Differences in the percentage of variance in dose explained by VKORC1 across race were largely accounted for by the frequency of the -1639A (or 1173T) allele. Thus, clinicians should recognize that, although at a population level, the contribution of VKORC1 toward dose requirements is higher in whites than in nonwhites; genotype predicts similar dose requirements across racial groups.Blood 03/2010; 115(18):3827-34. · 9.90 Impact Factor -
Article: THROMBOSIS AND HEMOSTASIS Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups
Blood 01/2010; 115(18):3827-3834. · 9.90 Impact Factor -
Article: Interactive modeling for ongoing utility of pharmacogenetic diagnostic testing: application for warfarin therapy.
[show abstract] [hide abstract]
ABSTRACT: The application of pharmacogenetic results requires demonstrable correlations between a test result and an indicated specific course of action. We developed a computational decision-support tool that combines patient-specific genotype and phenotype information to provide strategic dosage guidance. This tool, through estimating quantitative and temporal parameters associated with the metabolism- and concentration-dependent response to warfarin, provides the necessary patient-specific context for interpreting international normalized ratio (INR) measurements. We analyzed clinical information, plasma S-warfarin concentration, and CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genotypes for 137 patients with stable INRs. Plasma S-warfarin concentrations were evaluated by VKORC1 genotype (-1639G>A). The steady-state plasma S-warfarin concentration was calculated with CYP2C9 genotype-based clearance rates and compared with actual measurements. The plasma S-warfarin concentration required to yield the target INR response is significantly (P < 0.05) associated with VKORC1 -1639G>A genotype (GG, 0.68 mg/L; AG, 0.48 mg/L; AA, 0.27 mg/L). Modeling of the plasma S-warfarin concentration according to CYP2C9 genotype predicted 58% of the variation in measured S-warfarin concentration: Measured [S-warfarin] = 0.67(Estimated [S-warfarin]) + 0.16 mg/L. The target interval of plasma S-warfarin concentration required to yield a therapeutic INR can be predicted from the VKORC1 genotype (pharmacodynamics), and the progressive changes in S-warfarin concentration after repeated daily dosing can be predicted from the CYP2C9 genotype (pharmacokinetics). Combining the application of multivariate equations for estimating the maintenance dose with genotype-guided pharmacokinetics/pharmacodynamics modeling provides a powerful tool for maximizing the value of CYP2C9 and VKORC1 test results for ongoing application to patient care.Clinical Chemistry 09/2009; 55(10):1861-8. · 7.91 Impact Factor -
Article: Anemia: an independent predictor of death and hospitalizations among elderly patients with atrial fibrillation.
[show abstract] [hide abstract]
ABSTRACT: Anemia and atrial fibrillation (AF) are common among the elderly. Anemia is an independent predictor of mortality and morbidity for numerous cardiovascular and noncardiovascular diseases, but the association of anemia with mortality and hospitalizations in patients with AF requires clarification. Subjects were 13,067 Medicare beneficiaries hospitalized with AF and included in the National Registry of Atrial Fibrillation II data set. Index hospitalization hematocrit (Hct) was obtained by structured chart abstraction. Cox proportional hazards models quantified the association of Hct with mortality and re-hospitalizations during a median follow-up period of 12 months. The mean age was 79.8 years, 58% were women, and the mean Hct was 39.2%. Hematocrit was significantly (P < .0001) associated with risk of death and of rehospitalization even after adjustment for demographic information, comorbid conditions, and use of cardiovascular medications. As compared to a Hct of 40% to 44.9%, the adjusted hazard ratios for mortality were 1.66 for Hct <25%, 1.50 for 25% to 29.9%, 1.28 for 30% to 34.9%, 1.07 for 35% to 39.9%, 1.03 for 45% to 49.9%, and 1.10 for > or = 50%. The association between anemia and mortality was significant in men and women but stronger in men (P = .006 for interaction). Compared to the category 40% to 44.9%, the risk of rehospitalization was increased to 28% (adjusted hazard ratio 1.28, 95% CI 1.15-1.43) in the Hct category 25% to 29.9%. Anemia is an independent predictor of mortality and of hospitalizations in elderly patients with AF. Studies are needed to assess the effect of treatment of anemia on clinical outcomes.American heart journal 06/2009; 157(6):1057-63. · 4.65 Impact Factor -
Article: Cost-effectiveness of using pharmacogenetic information in warfarin dosing for patients with nonvalvular atrial fibrillation.
[show abstract] [hide abstract]
ABSTRACT: Variants in genes involved in warfarin metabolism and sensitivity affect individual warfarin requirements and the risk for bleeding. Testing for these variant alleles might allow more personalized dosing of warfarin during the induction phase. In 2007, the U.S. Food and Drug Administration changed the labeling for warfarin (Coumadin, Bristol-Myers Squibb, Princeton, New Jersey), suggesting that clinicians consider genetic testing before initiating therapy. To examine the cost-effectiveness of genotype-guided dosing versus standard induction of warfarin therapy for patients with nonvalvular atrial fibrillation. Markov state transition decision model. MEDLINE searches and bibliographies from relevant articles of literature published in English. Outpatients or inpatients requiring initiation of warfarin therapy. The base case was a man age 69 years with newly diagnosed nonvalvular atrial fibrillation and no contraindications to warfarin therapy. Lifetime. Societal. Genotype-guided dosing consisting of genotyping for CYP2C9*2, CYP2C9*3, and/or VKORC1 versus standard warfarin induction. Effectiveness was measured in quality-adjusted life-years (QALYs), and costs were in 2007 U.S. dollars. In the base case, genotype-guided dosing resulted in better outcomes, but at a relatively high cost. Overall, the marginal cost-effectiveness of testing exceeded $170 000 per QALY. On the basis of current data and cost of testing (about $400), there is only a 10% chance that genotype-guided dosing is likely to be cost-effective (that is, <$50 000 per QALY). Sensitivity analyses revealed that for genetic testing to cost less than $50 000 per QALY, it would have to be restricted to patients at high risk for hemorrhage or meet the following optimistic criteria: prevent greater than 32% of major bleeding events, be available within 24 hours, and cost less than $200. Few published studies describe the effect of genotype-guided dosing on major bleeding events, and although these studies show a trend toward decreased bleeding, the results are not statistically significant. Warfarin-related genotyping is unlikely to be cost-effective for typical patients with nonvalvular atrial fibrillation, but may be cost-effective in patients at high risk for hemorrhage who are starting warfarin therapy.Annals of internal medicine 01/2009; 150(2):73-83. · 16.73 Impact Factor -
Article: Performance of commercial platforms for rapid genotyping of polymorphisms affecting warfarin dose.
[show abstract] [hide abstract]
ABSTRACT: Initiation of warfarin therapy is associated with bleeding owing to its narrow therapeutic window and unpredictable therapeutic dose. Pharmacogenetic-based dosing algorithms can improve accuracy of initial warfarin dosing but require rapid genotyping for cytochrome P-450 2C9 (CYP2C9) *2 and *3 single nucleotide polymorphisms (SNPs) and a vitamin K epoxide reductase (VKORC1) SNP. We evaluated 4 commercial systems: INFINITI analyzer (AutoGenomics, Carlsbad, CA), Invader assay (Third Wave Technologies, Madison, WI), Tag-It Mutation Detection assay (Luminex Molecular Diagnostics, formerly Tm Bioscience, Toronto, Canada), and Pyrosequencing (Biotage, Uppsala, Sweden). We genotyped 112 DNA samples and resolved any discrepancies with bidirectional sequencing. The INFINITI analyzer was 100% accurate for all SNPs and required 8 hours. Invader and Tag-It were 100% accurate for CYP2C9 SNPs, 99% accurate for VKORC1 -1639/3673 SNP, and required 3 hours and 8 hours, respectively. Pyrosequencing was 99% accurate for CYP2C9 *2, 100% accurate for CYP2C9 *3, and 100% accurate for VKORC1 and required 4 hours. Current commercial platforms provide accurate and rapid genotypes for pharmacogenetic dosing during initiation of warfarin therapy.American Journal of Clinical Pathology 07/2008; 129(6):876-83. · 2.60 Impact Factor -
Article: CYP4F2 genetic variant alters required warfarin dose.
[show abstract] [hide abstract]
ABSTRACT: Warfarin is an effective, commonly prescribed anticoagulant used to treat and prevent thrombotic events. Because of historically high rates of drug-associated adverse events, warfarin remains underprescribed. Further, interindividual variability in therapeutic dose mandates frequent monitoring until target anticoagulation is achieved. Genetic polymorphisms involved in warfarin metabolism and sensitivity have been implicated in variability of dose. Here, we describe a novel variant that influences warfarin requirements. To identify additional genetic variants that contribute to warfarin requirements, screening of DNA variants in additional genes that code for drug-metabolizing enzymes and drug transport proteins was undertaken using the Affymetrix drug-metabolizing enzymes and transporters panel. A DNA variant (rs2108622; V433M) in cytochrome P450 4F2 (CYP4F2) was associated with warfarin dose in 3 independent white cohorts of patients stabilized on warfarin representing diverse geographic regions in the United States and accounted for a difference in warfarin dose of approximately 1 mg/day between CC and TT subjects. Genetic variation of CYP4F2 was associated with a clinically relevant effect on warfarin requirement.Blood 05/2008; 111(8):4106-12. · 9.90 Impact Factor -
Article: Pharmacogenetics of warfarin: regulatory, scientific, and clinical issues.
[show abstract] [hide abstract]
ABSTRACT: Using pharmacogenetics-based therapy, clinicians can estimate the therapeutic warfarin dose by genotyping patients for single nucleotide polymorphisms (SNPs) that affect warfarin metabolism or sensitivity. SNPs in the cytochrome P450 complex (CYP2C9) affect warfarin metabolism: patients who have the CYP2C9*2 and/or CYP2C9*3 variants metabolize warfarin slowly and are more likely to have an elevated International Normalized Ratio INR or to hemorrhage during warfarin initiation than patients without these variants. SNPs in vitamin K epoxide reductase (VKORC1) correlate with warfarin sensitivity. Patients who are homozygous for a common VKORC1 promoter polymorphism, -1639 G>A (also designated as VKOR 3673, haplotype A, or haplotype*2), are warfarin sensitive and typically require lower warfarin doses. By providing an estimate of the therapeutic warfarin dose, pharmacogenetics-based therapy may improve the safety of anticoagulant therapy. To improve drug safety, the FDA updates labels of previously approved drugs as new clinical and genetic evidence accrues. The labels of medical products serve to inform prescribers and patients about potential ways to improve the benefit/risk ratio and/or optimize doses of medical products. On August 16, 2007, the FDA updated the label of warfarin to include information on pharmacogenetic testing and to encourage, but not require, the use of this information in dosing individual patients initiating warfarin therapy. The FDA completed the label update in August 2007.Journal of Thrombosis and Thrombolysis 03/2008; 25(1):45-51. · 1.48 Impact Factor -
Article: Optimal initial dose adjustment of warfarin in orthopedic patients.
[show abstract] [hide abstract]
ABSTRACT: Warfarin sodium is commonly prescribed for the prophylaxis and treatment of venous thromboembolism. Dosing algorithms have not been widely adopted because they require a fixed initial warfarin dose (eg, 5 mg) and are not tailored to other factors that may affect the international normalized ratio (INR). To develop an algorithm that could predict a therapeutic warfarin dose based on drug interactions, INR response after the initial warfarin doses, and other clinical factors. We used stepwise regression to quantify the relationship between these factors in patients beginning prophylactic warfarin therapy immediately prior to joint replacement. In the derivation cohort (n = 271), we separately modeled the therapeutic dose after 2 and 3 initial doses. We prospectively validated these 2 models in an independent cohort (n = 105). About half of the therapeutic dose variability was predictable after 3 days of therapy: R2 was 53% in the derivation cohort and 42% in the validation cohort. INR response after 3 warfarin doses (INR3) inversely correlated with therapeutic dose (p < 0.001). Intraoperative blood loss transiently, but significantly, elevated the postoperative INR values. Other significant (p < 0.03) predictors were the first and second warfarin doses (+7% and +6%, respectively, per 1 mg), and statin use (-15.0%). The model derived after 2 warfarin doses explained 32% of the variability in therapeutic dose. We developed and validated algorithms that estimate therapeutic warfarin doses based on clinical factors and INR response available after 2-3 days of warfarin therapy. The algorithms are implemented online at www.WarfarinDosing.org.Annals of Pharmacotherapy 12/2007; 41(11):1798-804. · 2.13 Impact Factor -
Article: Genetic-based dosing in orthopedic patients beginning warfarin therapy.
[show abstract] [hide abstract]
ABSTRACT: 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.Blood 10/2007; 110(5):1511-5. · 9.90 Impact Factor -
Article: The Association of Warfarin Use With Osteoporotic Fracture in Elderly Patients With Atrial Fibrillation-Reply.
Archives of internal medicine 07/2006; 166(14):1525. · 11.46 Impact Factor -
Article: Use and effectiveness of warfarin in Medicare beneficiaries with atrial fibrillation.
[show abstract] [hide abstract]
ABSTRACT: More than 2 million Americans have atrial fibrillation, and without antithrombotic therapy, their stroke rate is increased 5-fold. In randomized controlled trials, warfarin prevented 65% of ischemic strokes (hazard ratio [HR], 0.35; 95% CI, 0.26 to 0.48) compared with no antithrombotic therapy. However, the effectiveness of warfarin therapy outside of clinical trials is unknown, especially in black and Hispanic populations. Our goal was to quantify use of warfarin therapy, frequency of International Normalized Ratio monitoring, and effectiveness for stroke prophylaxis in Medicare beneficiaries with atrial fibrillation. This was a cohort study of Medicare beneficiaries with atrial fibrillation who were hospitalized between March 1998 and April 1999 in all 50 US states. The primary outcome was incident hospitalizations for ischemic stroke based on validated International Classification of Diseases, 9th Revision, Clinical Modification codes. Two thirds of ideal anticoagulation candidates were prescribed warfarin on hospital discharge. In unadjusted analyses, the stroke rates per 100 patient years of warfarin therapy were 5.2 in (non-Hispanic) white Medicare beneficiaries, 10.6 in black beneficiaries, and 12.2 in Hispanic beneficiaries. After adjusting for comorbid conditions, warfarin prescription was more frequent and monitoring more regular in white Medicare beneficiaries than in black or Hispanic beneficiaries (P<0.0001). Warfarin use was associated with 35% fewer ischemic strokes (HR, 0.65; 95% CI, 0.55 to 0.76) compared with no antithrombotic therapy but was less effective in black and Hispanic beneficiaries (P for interaction=0.048). The use, monitoring, and effectiveness of warfarin therapy are suboptimal in Medicare beneficiaries, especially in black and Hispanic beneficiaries.Stroke 05/2006; 37(4):1070-4. · 5.73 Impact Factor -
Article: Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF).
[show abstract] [hide abstract]
ABSTRACT: Although warfarin and other anticoagulants can prevent ischemic events, they can cause hemorrhage. Quantifying the rate of hemorrhage is crucial for determining the risks and net benefits of prescribing antithrombotic therapy. Our objective was to find a bleeding classification scheme that could quantify the risk of hemorrhage in elderly patients with atrial fibrillation. We combined bleeding risk factors from existing classification schemes into a new scheme, HEMORR2HAGES, and validated all bleeding classification schemes. We scored HEMORR2HAGES by adding 2 points for a prior bleed and 1 point for each of the other risk factors: hepatic or renal disease, ethanol abuse, malignancy, older (age > 75 years), reduced platelet count or function, hypertension (uncontrolled), anemia, genetic factors, excessive fall risk, and stroke. We used data from quality improvement organizations representing 7 states to assemble a registry of 3791 Medicare beneficiaries with atrial fibrillation. There were 162 hospital admissions with an International Classification of Diseases, Ninth Revision, Clinical Modification code for hemorrhage. With each additional point, the rate of bleeding per 100 patient-years of warfarin increased: 1.9 for 0, 2.5 for 1, 5.3 for 2, 8.4 for 3, 10.4 for 4, and 12.3 for > or =5 points. In patients prescribed warfarin, HEMORR2HAGES had greater predictive accuracy (c statistic 0.67) than other bleed prediction schemes (P < .001). Adaptations of existing classification schemes, especially a new bleeding risk scheme, HEMORR2HAGES, can quantify the risk of hemorrhage and aid in the management of antithrombotic therapy.American heart journal 04/2006; 151(3):713-9. · 4.65 Impact Factor
Top co-authors
Top Journals
Institutions
-
2002–2011
-
University of Washington Seattle
- • Department of Medicine
- • Division of General Internal Medicine
Seattle, WA, USA
-
-
2004–2010
-
Washington University in St. Louis
- Department of Medicine
Saint Louis, MO, USA
-
-
2009
-
University of Cincinnati
Cincinnati, OH, USA
-
-
2003
-
Barnes Jewish Hospital
Saint Louis, MO, USA
-
