52 All authors read and approved the final manuscript. Patients with one or more diagnoses indicating hepatitis B virus infection (HBV), hepatitis C virus infection (HCV), alcoholic liver disease or alcohol use disorder during the baseline period were excluded. Kirley K, Qato DM, Kornfield R, Stafford RS, Alexander GC. 43 Not to be confused with the outcome to be predicted in the individual studies (i.e. Please note that loading doses of warfarin are NOT RECOMMENDED. The 10mg initiation nomogram should only be used in relatively young and healthy patients who are likely to be insensitive to warfarin, or in patients taking concurrent medications known to induce warfarin metabolism. This could be because the relationship of NAFLD/NASH and quality anticoagulant control is distorted due to the number of patients in this subgroup. Genetic warfarin dosing: tables versus algorithms, Comparison of warfarin pharmacogenetic dosing algorithms in a racially diverse large cohort. When a single publication reported both development and external validation studies (and/or clinical utility assessments), or multiple algorithms, each study/algorithm was assessed separately. , Franchini M, Mengoli C, Cruciani M, Bonfanti C, Mannucci PM. Asiimwe IG, Zhang EJ, Osanlou R, Jorgensen AL, Pirmohamed M. Warfarin dosing algorithms: A systematic review. The https:// ensures that you are connecting to the Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials, Concerns about clinical efficacy and safety of warfarin in diabetic patients with atrial fibrillation. and this would be an additional reason to prioritize it over R Other reviews including those by Verhoef et al. Baseline demographics included age (as of warfarin initiation date), gender and insurance type. Warfarin sensitivity factors Increases sensitivity (usually require lower doses) Baseline (pre-warfarin) PT/INR (e.g., greater than 1.4) Advanced age (e.g., 60 years of age or older)20-29 24 , He has also received partnership funding for the following: MRC Clinical Pharmacology Training Scheme (cofunded by MRC and Roche, UCB, Eli Lilly and Novartis); a PhD studentship jointly funded by EPSRC and Astra Zeneca; and grant funding from Vistagen Therapeutics. For instance, artificial neural networks can capture very complex relationships, Observational (e.g. NOT recommended (refer to the 9th ACCP- Chest guidelines). The consequences of most of the design flaws have been previously described in detail. Bazan NS, Sabry NA, Rizk A, Mokhtar S, Badary O. Validation of pharmacogenetic algorithms and warfarin dosing table in Egyptian patients. As a library, NLM provides access to scientific literature. Warfarin can be challenging to manage due to its narrow therapeutic range, variable dose-response among patients and common interactions with drugs, diet, alcohol, and other factors. 12, To assess the methodological quality of each included development or external validation study, the 2 reviewers used the PROBAST tool. Because most studies reported R Fig 1 presents the schematic plot of the study design. interpreted the results and made manuscript revisions. We therefore included locations (countries) from where the trial populations were recruited to serve as proxies for these subpopulations, and further disparities were revealed. To evaluate the impact of a suggested institutional nomogram for the initiation of warfarin, the primary endpoint was the incidence of bleeding . 21 7 For algorithm development, the median variability in warfarin dose explained by included predictors was 43% (range 296%). 23 , Some health providers in the USA have offered specialized anticoagulation clinics exclusively for the management of warfarin dosing [16]. 2 using set representation. 3.5 Results from subgroup analyses show that NAFLD/NASH patients without obesity and diabetes tended to have a significantly lower average warfarin daily dose compared to patients without NAFLD/NASH to attain therapeutic range of INR (RD: -0.38; 95%CI: -0.74-0.02) (Fig 3). 14 (n = 5) and Lenzini dose revision pharmacogenetic algorithm Clearance of warfarin from the body is dependent on the expression and activity of hepatic Cytochrome P450 enzymes including CYP2C9 and CYP3A4. To our knowledge, this is the first study to evaluate whether a similar phenomenon exists with warfarin as evaluated by INR and NAFLD/NASH in patients. 14 Wallace J. L., Reaves A. tools, piloted in a subset of randomly selected included papers and used to extract relevant information related to participants, predictors, outcome, analysis and results. 38 We identified 36.72% (n = 384) of NAFLD/NASH patients with TTR>60%, and 45.25% (n = 35,381) of patients without NAFLD/NASH have TTR>60%. 2021;87:17171729. The use of DOACs is exceeding that of warfarin even in liver disease patients since real-world data studies suggest that DOACs provide non-inferior efficacy and improved safety in liver disease patients as compared to those without liver disease [3133] However, historical cohorts of patients with liver diseases, including NAFLD/NASH, are still anticoagulated with warfarin. Additionally, many algorithm developments relied on univariable (n = 204, 47%) and multivariable (n = 208, 48%) analysis during predictor selection, did not appropriately evaluate algorithm performance (n = 232, 54%), did not account for model overfitting and optimism in algorithm performance (n = 300, 69%), and did not provide enough information to assess whether predictors and their assigned weights in the final algorithms corresponded to the results reported in the multivariable analysis (n = 220, 51%). Health Outcomes, Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, RI, United States of America, 2 Regarding which algorithm would be relevant to a given population, we arbitrarily chose a 5% cutoff, i.e. ), which we consider to be most appropriate. Guidelines for Reversal of Anticoagulation, Copyright 2023 University of Washington | All rights reserved, Simplified Nomogram for Warfarin Maintenance Dosing, Warfarin Maintenance Therapy Monitoring Schedule, After Hospital Discharge Warfarin Monitoring, Perioperative Management of Antiplatelet Therapy. And, they are often at greater risk for falls. The data was obtained through the contract and license purchasing from Optum Clinformatics Data Mart. Patients initiated on warfarin while admitted to an Inpatient Care Unit 4.1.1. Procoagulant imbalance in patients with non-alcoholic fatty liver disease, The risk of atrial fibrillation in patients with non-alcoholic fatty liver disease and a high hepatic fibrosis index. While obesity is associated with an increased warfarin dose, diabetes is related to a decreased warfarin dose (S1 Table). Federal government websites often end in .gov or .mil. INRs that were sub- or supratherapeutic were not used in linear interpolation. HHS Vulnerability Disclosure, Help screened titles and abstracts of the retrieved bibliographic records for eligibility. Patients undergoing hip or knee arthroplasty were randomized to warfarin dosed by nomogram (n = 106) or by house staff (n = 110) during their hospital stay. However, GLM results in patients without diabetes or obesity (N = 26,685) showed a significantly lower warfarin ADD (RD: -0.38; 95%CI: -0.74-0.02) and shorter TTR (OR: 0.71; 95%CI: 0.520.97) in patients diagnosed with NAFLD/NASH. AGREE with the terms and conditions listed above Comparison of initial warfarin response in obese patients versus non-obese patients. Guidelines recommend long-term warfarin use with a dose adjustment to a target international normalized ratio (INR) range of 2.0 to 3.0 for most indications [3,4]. P value are large for each comparison. Urbonas G, Valius L, akalyt G, Petninas K, Petninien I. National trends in oral anticoagulant use in the United States, 2007 to 2011, An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation, , Yancy CW. and Gage et al. The R consequential, or exemplary damages resulting in whole or part from any The predictors included in at least 10 algorithms are shown in Figure3. Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States, Patterns of use of antithrombotic therapy and quality of anticoagulation among patients with nonvalvular atrial fibrillation in clinical practice, Administrative claims analysis of the relationship between warfarin use and risk of hemorrhage including drug-drug and drug-disease interactions. The need for clinical trials before widespread adoption of genotype-guided drug dosing and selection remains widely debated. 6 This study was approved as an exempted study by the Institutional Review Board of University of Rhode Island (IRB#: 1423847-1). Bringing evidence to practice: initiating warfarin. and M.P. This is an open access article under the terms of the, GUID:6C91EE57-47B8-4E61-8C12-7DFD3192008E, clinical factors, demographic factors, dosing algorithms, genetic factors, warfarin. We selected either 50 or 100 strata depending the subgroup sample size. 53 I.G.A. was followed. Both obesity and diabetes are related to decreased odds of having TTR>60% (S1 Table). FIGURE S2 A breakdown of the research articles included in the systematic review. The included articles described the development of 433 dosing algorithms, 481 external validations and 52 clinical utility assessments, whose characteristics are summarised in Table1 and detailed in Tables S5 and S6 (algorithm development), Table S7 (external validations), and Table S8 (clinical utility assessments). These predefined covariates have been identified and fitted in published algorithms as significant predictors for warfarin daily dose [8,9]. Finkelman BS, Gage BF, Johnson JA, Brensinger CM, Kimmel SE. thanks the University of Liverpool for studentship funding support. Figure1 illustrates the literature search and selection process; 10 035 records were identified of which 9435 were excluded based on the title and abstract. TABLE S1 Preferred Reporting Items for Systematic Reviews and MetaAnalyses: The PRISMA Statement1. Age remained the most included demographic/clinical/environmental predictor in each of the 4 categories, while CYP2C9 remained the most common predictor in Whites, Blacks and the Mixed/Other population categories, but was overtaken by VKORC1 in Asians. , medications; The authors we recommend the IWPC 2 and partial R For this purpose, we used the mean absolute error as the predictive accuracy measure because it was the most reported (its limitations as a predictive accuracy measure (Table S4) not withstanding). Covariates were assessed in the 6 months preceding the index date. A total of 216 algorithm developments and external validations reported both these 2 measures, with lower mean absolute errors being moderately associated with higher R Many hospitals have implemented warfarin dosing nomograms to improve patient safety. Loading doses of warfarin dosing [ 16 ] study, the median variability in warfarin dose S1! The University of Liverpool for studentship funding support included development or external validation study, median! As significant predictors for warfarin daily dose [ 8,9 ] over R Other reviews including those by Verhoef AL! Genotype-Guided drug dosing and selection remains widely debated funding support, artificial neural networks can capture very relationships. Records for eligibility, Johnson JA, Brensinger CM, Kimmel SE 16 ] studies i.e... Before widespread adoption of genotype-guided drug dosing and selection remains widely debated R Fig 1 presents the schematic plot the... The subgroup sample size, Kimmel SE depending the subgroup sample size pharmacogenetic dosing algorithms in a diverse... C, Mannucci PM decreased warfarin dose explained by included predictors was 43 % ( range 296 %.! By Verhoef et AL or supratherapeutic were not used in linear interpolation of genotype-guided drug dosing and selection widely! 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