Achieving therapeutic anticoagulation with warfarin is complicated by substantial inter-patient and intra-patient variability with numerous factors known to influence dose requirements. Obesity is one factor for which there remains no study to date investigating its initial effect on warfarin response assessed by INR, stratified by BMI category in hospitalized patients. To compare initial warfarin response between obese and non-obese patients by evaluating average daily dose (ADD), time required to attain therapeutic INR, and mean discharge dose (MDD), stratified by BMI category. A retrospective review was conducted to evaluate initial warfarin response in hospitalized patients of different BMI categories initiated on warfarin with ≥4 consecutive days of therapy and managed by pharmacy dosing service. 211 patients were included (10 underweight, 45 normal weight, 48 overweight, 71 obese, 37 morbidly obese). Across BMI categories, the percentage of patients attaining therapeutic INR prior to discharge differed (p = 0.0004) with 71.1 % of normal weight therapeutic compared to 42.3 % of obese and 38 % of morbidly obese. Within BMI categories, when comparing ADD between patients therapeutic and subtherapeutic at discharge, no differences were observed, except among overweight patients (5.6 ± 0.3 vs. 7 ± 0.4 mg, p = 0.0143). Compared to normal weight, obese and morbidly obese required a significantly longer median time to achieve therapeutic INR (8 and 10 days vs. 6 days) and a higher ADD (6.6 ± 0.3 and 7.6 ± 0.5 vs. 5 ± 0.3 mg) and MDD (6.7 ± 0.5 and 6.7 ± 0.7 vs. 4.4 ± 0.5 mg). Compared to normal weight, obese and morbidly obese patients had a decreased initial response to warfarin.
Warfarin Obesity Initial dosing
This is a preview of subscription content, log in to check access.
Financial support for this project was provided in part by the University of Tennessee Health Science Center and Methodist University Hospital.
Conflict of interest
The authors declare that they have no conflict of interest.
Oake N, Fergusson DA, Forster AJ, van Walraven C (2007) Frequency of adverse events in patients with poor anticoagulation: a meta-analysis. CMAJ 176:1589–1594PubMedGoogle Scholar
Holbrook A, Schulman S, Witt DM et al (2012) Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141:152S–184SCrossRefGoogle Scholar
Garcia D, Regan S, Crowther M, Hughes RA, Hylek EM (2005) Warfarin maintenance dosing patterns in clinical practice: implications for safer anticoagulation in the elderly population. Chest 127:2049–2056PubMedCrossRefGoogle Scholar
Aithal GP, Day CP, Kesteven PJ, Daly AK (1999) Association of polymorphisms in cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 353:717–719PubMedCrossRefGoogle Scholar
Schwarz UI, Ritchie D, Bradford Y, Li C, Dudek SM, Frye-Anderson A, Kim RB, Roden DM, Stein CM (2008) Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med 358:999–1008PubMedCrossRefGoogle Scholar
Gage BF, Eby C, Milligan PE, Banet GA, Duncan JR, McLeod HL (2004) Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin. Thromb Haemost 91:87–94PubMedGoogle Scholar
Eichenger S, Hron G, Bialonczyk C et al (2008) Overweight, obesity and the risk of recurrent venous thromboembolism. Arch Intern Med 168(15):1678–1683CrossRefGoogle Scholar
Zu Schwabedissen CM, Schmitz VMF, Woodruff S et al (2006) Obesity is associated with a slower response to initial phenprocoumon therapy whereas CYP2C9 genotypes are not. Eur J Clin Pharmacol 62:713–720CrossRefGoogle Scholar
National Institutes of Health (1998) Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. Obes Res 6(Suppl 2):51S–209SGoogle Scholar
Kamali F, Khan TI, King BP et al (2004) Contribution of age, body size, and CYP2C9 genotype to anticoagulant response to warfarin. Clin Pharmacol Ther 75:204–212PubMedCrossRefGoogle Scholar
Ageno W, Steid L, Ultori C et al (2003) The initial phase of oral anticoagulation with warfarin in outpatients with deep venous thrombosis. Blood Coagul Fibrinolysis 14:11–14PubMedCrossRefGoogle Scholar
Gage BF, Eby C, Johnson JA et al (2008) Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther 84:326–331PubMedCrossRefGoogle Scholar