Low dose regimens – background info

Comments from Ansel et al. 1

Most patients can be started on 5 to 10mg for the first 1-2 days.  Patients who are at an increased risk of bleeding such as the elderly or patients with CHF/ liver dx / debilitated / recent major surgery / or patients receiving medications known to potentiate the action of warfarin, should be started on leq 5mg.  -In all cases, subsequent dosing should be based on the INR response.

Comments from Garcia et al. 2

Patients: A total of 4,616 patients comprised the prospective cohort, and 7,586 patients comprised the retrospective cohort. Of the 12,202 patients, 2,359 were >/= 80 years of age. Measurements: Median weekly and daily maintenance warfarin dose. ”

“Results: The warfarin dose was inversely related to age and was strongly associated with gender. The median weekly dose ranged from 45 mg (6.4 mg/d) for men who were < 50 years of age to 22 mg (3.1 mg/d) for women > 80 years of age. The weekly dose declined by 0.4 mg/yr (95% confidence interval [CI], 0.37 to 0.44; p < 0.001) and women required 4.5 mg less per week than men (95% CI, 3.8 to 5.3; p < 0.001). Among patients who were > 70 years of age, the often-suggested initiation dose of 5 mg/d will be excessive for 82% of women and 65% of men.
Currently, few data are available to guide clinicians in the dosing of warfarin therapy for the very elderly.”

We found highly significant associations between warfarin dose and age, and warfarin dose and gender in two large cohorts. For each additional year of age, the weekly warfarin dose declined by 0.4 mg.

Comments from Janes et al. 3

Direct quotes from Medline abstract:
“A new protocol for initiating warfarin therapy was introduced to reduce the workload in the Anticoagulant Clinic. A total of 200 outpatients, with a median age of 74 years, requiring anticoagulation for atrial fibrillation, commenced warfarin 3 mg daily for 1 week. ”

“Patients were initially seen weekly, and subsequent warfarin doses were dictated by the International Normalized Ratio (INR) on days 8 and 15; 84% of patients followed the protocol correctly: of these 86% had an INR > or =2 by day 15 and >98% had INR >2 by day 22. By day 22, 58% of patients achieved a stable dose, 85% by day 29 and >95% by day 36. Day 8 INR was predictive of the final maintenance dose required. ”

“No patient suffered any thrombotic or haemorrhagic complications in the first month: only three patients had an INR >3 on day 8, and 11 patients had an INR >4 on day 15. Patient age and sex were not sufficiently related to warfarin requirement to provide useful predictive information. ”

“This protocol, requiring only weekly INRs, has proved safe and effective for outpatient warfarinization, and has reduced clinic attendances in this population.”

(outside source – utilizes Janes et al. nomogram)
BPACnz – evidence-based guidelines: Additional guidance
janes nomogram

Comments from Manning DM. 4

“For a warfarin-naïve octogenarian, especially in the presence of polypharmacy and co-morbidities, a more appropriate initiating dose might be 3 or 3.5 mg rather than 5 mg. ”

“Hylek characterized, by age group, the daily warfarin requirements of 1787 outpatients, each with a target INR range 2.0-3.0. Thus, the most commonly encountered daily maintenance dose requirement for patients of age <65 is ~6mg, age 65-75 is ~ 4mg, age 76-80 is ~3.5 mg, and age >80 is ~3 mg.

Hylek EM. Oral anticoagulants: pharmacologic issues for use in the elderly. Clinics in Geriatric Medicine. 2001; 17: 1-12.
The Brody School of Medicine
Department of Family Medicine

Evidence-Based Medicine Resources
Warfarin Initiation Protocols for Elderly Patients