Three-monthly warfarin assessment ‘feasible’
MedWire News: Assessment of warfarin dosing every 3 months is not inferior to monthly assessment in terms of the percentage of time spent in the therapeutic international normalized ratio (INR) range, Canadian researchers report.
This contradicts the American College of Chest Physicians recommendation that patients receiving warfarin undergo INR monitoring every 4 weeks, note Sam Schulman and colleagues, from McMaster University in Hamilton, Ontario.
However, a 1998 British guideline suggests that INR monitoring can be extended to 3-monthly intervals for very stable patients, although the evidence supporting this strategy is limited.
Therefore, to evaluate the safety and feasibility of such an extended interval, Schulman and team compared warfarin dose assessment every 4 weeks versus every 3 months in 250 patients whose warfarin maintenance dose had been unchanged in the previous 6 months.
To ensure the study was blinded, all patients attended the clinic every 4 weeks. Those in the 4-week group (n=126) had their true INR recorded at each visit, whereas patients in the 3-month group (n=124) had sham INRs within the target range recorded for two of the three 4-week periods.
The researchers report in the Annals of Internal Medicine that the percentage of time in the therapeutic range (TTR) was 74.1% in the 4-week group compared with 71.6% in the 3-month group. A test for noninferiority showed that a 3-month interval was not inferior to 4 weeks in terms of TTR.
In addition, significantly fewer patients in the 3-month group than in the 4-week group had any dose changes, at 37.1% versus 55.6%.
The higher proportion of dose changes in the 4-week group were probably "attributable to temporary fluctuations in the INR due to deviations in the diet or short-term use of an interacting drug," and may have been "unnecessary" in some cases, say the researchers.
Other secondary outcomes, namely number of extreme INRs, major bleeding events, objectively verified thromboembolism episodes, and death did not differ significantly between the groups.
Schulman et al say their findings suggest that the prolonged period between dose assessments is "safe and feasible." They caution, however, that the ongoing contact every 4 weeks could have increased adherence to treatment more than monitoring and contact every 3 months would have.
Therefore "a phase 3 trial comparing testing and contact every 4 weeks with every 12 weeks would be necessary before prolonged intervals for testing and dose assessment can be recommended for clinical practice," the team concludes.
By Laura Dean