title: Effect of Left Ventricular Systolic Dysfunction on Response to Warfarin.
abstract: Candidates for chronic warfarin therapy often have co-morbid conditions, such as heart failure, with reduced left ventricular ejection fraction. Previous reports have demonstrated an increased risk of over-anticoagulation due to reduced warfarin dose requirement in patients with decompensated heart failure. However, the influence of left ventricular systolic dysfunction (LVSD), defined as left ventricular ejection fraction <40%, on warfarin response has not been evaluated. Here, we assess the influence of LVSD on warfarin dose, anticoagulation control (percent time in target range), and risk of over-anticoagulation (international normalized ratio >4) and major hemorrhage. Of the 1,354 patients included in this prospective cohort study, 214 patients (16%) had LVSD. Patients with LVSD required 11% lower warfarin dose compared with those without LVSD (p <0.001) using multivariate linear regression analyses. Using multivariate Cox proportional hazards model, patients with LVSD experienced similar levels of anticoagulation control (percent time in target range: 51% vs 53% p = 0.15), risk of over-anticoagulation (international normalized ratio >4; hazard ratio 1.01, 95% confidence interval 0.82 to 1.25; p = 0.91), and risk of major hemorrhage (hazard ratio 1.11; 95% confidence interval 0.70 to 1.74; p = 0.66). Addition of LVSD variable in the model increased the variability explained from 35% to 36% for warfarin dose prediction. In conclusion, our results demonstrate that patients with LVSD require lower doses of warfarin. Whether warfarin dosing algorithms incorporating LVSD in determining initial doses improves outcomes needs to be evaluated.
authors.affiliation: Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Alabama.
authors.forename: Sameer
authors.initials: S
authors.lastname: Ather
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Alabama.
authors.forename: Aditi
authors.initials: A
authors.lastname: Shendre
authors.affiliation: Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Alabama.
authors.forename: T Mark
authors.initials: TM
authors.lastname: Beasley
authors.affiliation: Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Alabama.
authors.forename: Todd
authors.initials: T
authors.lastname: Brown
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Hill
authors.affiliation: Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Alabama.
authors.forename: Sumanth D
authors.initials: SD
authors.lastname: Prabhu
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Alabama. Electronic address: nlimdi@uab.edu.
authors.forename: Nita A
authors.initials: NA
authors.lastname: Limdi
mesh_terms: D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D015331:Cohort Studies; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D005260:Female; D006333:Heart Failure / Q000453:epidemiology / Q000503:physiopathology*; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D019934:International Normalized Ratio; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000188:drug therapy / Q000453:epidemiology; D058729:Peripheral Arterial Disease / Q000188:drug therapy / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D013318:Stroke Volume; D054556:Venous Thromboembolism / Q000188:drug therapy / Q000453:epidemiology; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology / Q000503:physiopathology*; D016277:Ventricular Function, Left; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin