Warfarin Dose Assessment Every 4 Weeks Versus Every 12 Weeks in Patients With Stable International Normalized Ratios Full Text
Annals of Internal Medicine, 11/18/2011
Schulman S et al. – Assessment of warfarin dosing every 12 weeks seems to be safe and noninferior to assessment every 4 weeks. A comparison of international normalized ratio (INR) testing, patient contact, and warfarin dose assessment every 12 weeks versus every 4 weeks is necessary before INR testing every 12 weeks can be routinely recommended for practice.Methods
- Noninferiority randomized trial.
- The randomization schedule (in a 1:1 ratio) was computer–generated, and allocation was concealed until the database was locked by using a centralized schedule.
- Patients, study and clinical personnel, adjudicators of clinical events, and the study statistician were blinded to treatment assignment.
- Single center in Hamilton, Ontario, Canada.
- 250 patients receiving long–term warfarin therapy, whose dose was unchanged for at least 6 months; 226 completed the study.
- Dosing assessment every 12 weeks (n = 124) compared with every 4 weeks (n = 126) for 12 months.
- Patients in the 12–week group were tested every 4 weeks; sham INRs within the target range were reported for two of the three 4–week periods.
- Percentage of time in the therapeutic range (primary outcome) and number of extreme INRs, changes in maintenance dose, major bleeding events, objectively verified thromboembolism, and death (secondary outcomes).
- The percentage of time in the therapeutic range was 74.1% (SD, 18.8%) in the 4–week group compared with 71.6% (SD, 20.0%) in the 12–week group (absolute difference, 2.5 percentage points [1–sided 97.5% upper confidence bound, 7.3 percentage points]; noninferiority P = 0.020 for a 7.5–percentage point margin).
- Fewer patients in the 12–week group than in the 4–week group had any dose changes (37.1% vs. 55.6%; absolute difference, 18.5 percentage points [95% CI, 6.1 to 30.0 percentage points]; P = 0.004).
- Secondary outcomes did not differ between groups.