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A Way to Start Warfarin in Patients with Atrial Fibrillation
Maintenance vs. Initiation Doses of Warfarin in the Elderly
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Ayumu Ono, MD Otsuki hospital
Send letter to journal:
otsukib{at}sky.quolia.com Ayumu Ono
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To the editor We read with interest the study by Garcia et al(1) on warfarin maintenance dosing patterns in clinical practice. The finding that the maintenance dose of warfarin was lower than 5 mg/day in the majority of patients aged > 70 years suggests that the commonly employed initiating dose of 5 mg/day will lead to overanticoagulation in elderly patients. Higher rates of bleeding and erratic international normalized ratio (INR) values that have been reported in the early phase of warfarin therapy(2) may in part be explained by overly aggressive dosing in the elderly. Moreover, currently available warfarin initiation nomograms are limited by their reliance on frequent laboratory testing that represents a significant burden and may be unrealistic for many elderly patients. A recent guideline also suggests a starting dose of <5 mg/day in elderly patients in order to prevent bleeding complications, but frequent laboratory testing as daily or alternate-day monitoring is still required.(3) Therefore, lower initiating dose without frequent monitoring should be considered for the elderly in the outpatient setting where significant barriers to daily monitoring exist. Although the authors suggest that the median maintenance dose can be an initiating dose, frequent monitoring should be made for warfarin initiation in the patients whose maintenance doses are lower than the median dose. Because anticoagulation is not necessarily urgent for atrial fibrillation (AF),(4) we start warfarin with the lowest maintenance dose (1 to 2 mg/day) without frequent monitoring in elderly outpatients with AF in actual clinical practice. Intervals between the INR tests vary from 1 to 4 weeks according to the decision of each attending physician. Additional dose of warfarin is given at each monitoring when the INR do not reach the target goal (INR: 1.5-2.5) recommended for elderly patients by the Japanese Guidelines for the Management of Stroke.(5) We followed up 37 outpatients (³70 years, mean 78) with AF to evaluate frequency of the INR test and days spent through warfarin initiation and the first achievement of the target goal. Outcomes including ischemic events and bleeding complications were also evaluated during the initiation period. The patients spend 49.6 days on average (7-14 days: 27%; 15-30 days: 19%; 31-60 days: 22%; 61 days²: 32%) and the mean interval of INR test was 14 days (7 days: 22%; 8-14 days: 43%; 15-21 days: 24%; 22-28 days: 11%) until the INR reached the target goal. There was a significant positive relationship between the interval of INR test and days spent for achievement of the target goal (r=0.734, p< 0.001). Ischemic events or bleeding complications did not occur during the initiation period. Although days spent for the first achievement of the target goal varied significantly from less than 2 weeks to more than 2 months, risk of stroke during the short term (up to 2 or 3 months) may be low because the annual stroke risk in most of patients with AF is less than 10%.(4) The mean warfarin dose required to reach the target goal was 2.3 ± 0.7 mg/day (mean ± SD). Overanticoagulation during the initiation period occurred only in 3 (8%) patients (INR: 3.95, 3.04, 2.56). Thus, warfarin initiation with the lowest maintenance dose without frequent monitoring may be a useful option in elderly outpatients with AF who have barriers to daily monitoring and do not need urgent anticoagulation. References 1. Garcia D, Regan S, Crowther M, et al. Warfarin maintenance dosing patterns in clinical practice: implications for safer anticoagulation in the elderly population. Chest 2005;127:2049-2056. 2. Fihn SD, McDonell M, Martin D, et al. Risk factors for complications of chronic anticoagulation. A multicenter study. Warfarin Optimized Outpatient Follow-up Study Group. Ann Intern Med 1993;118:511-520. 3. Ansell J, Hirsh J, Poller L, et al. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:204S-233S. 4. Singer DE, Albers GW, Dalen JE, et al. Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:429S-456S. 5. The Joint Committee on Guidelines for the Management of Stroke. Japanese Guidelines for the Management of Stroke. Tokyo: Kyowa Kikaku, 2004 (in Japanese). |
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Joseph I. Levine, Resident Physician Hennepin County Medical Center, Steven Hillson, MD
Send letter to journal:
levi0161{at}umn.edu Joseph I. Levine, et al.
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After review and discussion of the article entitled, “Warfarin Maintenance Dosing Patterns in Clinical Practice: Implications for Safer Anticoagulation in the Elderly Population” during our resident journal club, we were hoping that its authors would clarify and expand upon several issues. First, the “stable warfarin dose” as defined by the authors is a “dose that was prescribed twice consecutively after two in-range INR measurements” (p 2051). The authors previously state on page 2050 that their subjects “. . . had achieved a stable warfarin dose during the observation period.” We could not tell whether a portion of these patients were observed from initiation of warfarin, or whether all had been receiving warfarin for some time before the study period. Second, the authors suggest that their maintenance dosing results may be used as empiric initiation therapy for elderly patients in whom “daily testing is not possible.” Although appealing, we do not see how the data provided allow the average maintenance dose to be used to predict an individual initial dose. Do the authors have some data available about the initiation phase of the patients in their database, such as initial dosing and INR measures that might lend support to this idea? We are concerned that there may be no initiation strategy that can be considered safe in older patients when access to appropriate INR monitoring is unavailable. Finally, we are concerned about the possible role of body mass as a confounder. The authors did not control for body mass in the multivariate analysis. We suspect that the lower body mass of older patients could account for some or the entire decreased dose requirement. It would be helpful if the authors could repeat the analysis including body mass as a covariate. Thank you very much. Sincerely, Joseph Levine and Steven Hillson |
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