Initiating and Maintaining Patients on Warfarin Anticoagulation: The Importance of Monitoring

BACKGROUND: The VA Stroke Prevention in Nonrheumatic Atrial Fibrillation study was a prospective, randomized, double-blind study comparing low-dose warfarin with placebo in patients with nonrheumatic atrial fibrillation. The trial showed a 79% reduction in stroke rate in warfarin randomized patients without an increase in bleeding complications. We examined the need for frequent prothrombin time monitoring (international normalized ratios INR were not measured directly) in patients receiving warfarin.</P METHODS AND RESULTS: Patients were initiated on 4.0 mg/d warfarin with a goal of maintaining the prothrombin time ratio (PTR) within the range of 1.2-1.5 (estimated INR: 1.4-2.8). PTR monitoring was performed weekly during a 12-week induction period and monthly thereafter for a total follow-up of 3 years. Two hundred sixty patients were randomized to receive warfarin. During the induction period, the proportion of patients whose PTRs were in the desired range increased from 28% at 1 week postrandomization to 65% at 12 weeks postrandomization; the proportion of patients requiring a dose adjustment decreased from 52% to 16% during the same period. During the maintenance period, the mean proportion of patients whose PTRs were within 1.2-1.5 was 60.5% +/- 6.2%. CONCLUSIONS: Low-dose anticoagulation with warfarin in outpatients should be initiated at the anticipated maintainance dose. This approach reduces the chance of being out of range on the high side. Weekly INR estimation during this phase seems optimal. Considerable dose adjusting was required during the maintenance phase to keep patients within range; monthly INRs are required. Because of the need for dose adjustments, fixed-dose warfarin regimens are unlikely to keep patients in the desired narrow therapeutic range.