A New Regimen for Starting Warfarin Therapy in Out-Patients

Abstract

Aims Oral anticoagulation is increasingly used in elderly patients with atrial fibrillation to prevent embolic phenomena. The use of anticoagulants in this population is prophylactic rather than therapeutic and so there is no urgency to establish anticoagulation within the desired therapeutic range. The aim of the study was to develop an out-patient regimen for initiation of oral anticoagulation with warfarin which requires only weekly monitoring of the International Normalized Ratio (INR). Methods The study was undertaken in two phases. In the first phase, factors which predict the final maintenance dosage of warfarin were defined and used to build a decision tree and dosage algorithm. In the second study the algorithm was tested. Patients were given 2 mg warfarin daily for 2 weeks and the INR at this time was used to predict the maintenance dose. Patients then attended for weekly measurements of the INR until steady state had been reached. Dosage adjustments were not made unless the INR was >4.0 or <1.5 for 2 consecutive weeks. The accuracy of the prediction was measured by calculating the mean INR of weeks 6-8 and the number of patients in the target range 2.0-3.0 was determined. Results One hundred and seven consecutive out-patients (mean age 70 years range 64-86) completed the first study. The age, sex, height, weight, alcohol intake, number of cigarettes smoked, concomitant medication, clinical evidence of right heart failure, liver failure, abnormalities in liver enzyme estimations, baseline INR and INR after 2 weeks of 2 mg warfarin daily were used in a polytomous logistic regression analysis with stepwise inclusion of factors to determine which factors influenced the eventual maintenance dosage of warfarin. The INR after 2 weeks of 2 mg warfarin therapy predicted 70% of the variability of the maintenance dose. Of other factors only the sex of the patient had a large enough effect to be included in the prediction algorithm. One hundred and six patients (mean age 71 years range 50-85 years) completed the second study. Only one patient needed a dose adjustment in the first 2 weeks of warfarin 2 mg daily (INR 4.4). Overall, 60% patients were in the narrow target range (INR 2.0-3.0) at steady state. In five patients the INR was >4.0 at any visit after the second week and needed dosage adjustment. In four patients the INR was <1.5 at steady state. Conclusions We have developed a method of predicting the maintenance dose of warfarin in an elderly population based on the INR after 2 weeks of warfarin 2 mg daily, and the sex of the patient. This is a safe and convenient way of initiating warfarin therapy as an out-patient which requires only weekly INR checks.

Assessment of an Age-Adjusted Warfarin Initiation Protocol

“…[8][9][10][11] Comparisons of efficacy between studies is difficult because of different endpoints. We manage a primarily elderly population and prefer the approach of measuring consecutive INRs after each of the first 4 doses during initiation of warfarin therapy.…”

Pharmacogenetics of warfarin: regulatory, scientific, and clinical issues

“…In an attempt to decrease the toxicity of warfarin induction, several clinical dosing algorithms have been proposed [27][28][29][30][31][32], but none has been well accepted. A major barrier to their use is that they were developed for middle-aged inpatients who could tolerate doses of 5-10 mg warfarin daily and who had daily monitoring of the INR [27,28].…”

“…Today, the typical person taking warfarin is elderly [7,[33][34][35]. Because warfarin dose requirements decrease with age [36], use of existing algorithms tends to overdose the elderly [29][30][31][32]. A second factor that increases the risk of overdose is that many patients now begin warfarin in the outpatient setting, where daily INR monitoring is not feasible.…”

Impact of introducing anticoagulation-related prescribing guidelines in a hospital setting using academic detailing

“…Warfarin initiation approaches that were previously successful are now clearly too aggressive, and likely to overanticoagulate the patient (Roberts et al 1999; Gedge et al 2000). A number of more appropriate methods of warfarin initiation have since been developed (Oates et al 1998; Tait and Sefcick 1998, Crowther et al 1999; Roberts et al 1999). …”