Impact of global geographic region on time in therapeutic range on warfarin anticoagulant therapy: data from the ROCKET AF clinical trial.

Vitamin k antagonist (vka) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. time in therapeutic range (ttr) is a widely cited measure of the quality of vka therapy. we sought to identify factors associated with ttr in a large,international clinical trial. ttr (international normalized ratio [inr] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the rocket af trial. factors associated with ttr at the individual patient level (i-ttr) were determined via multivariable linear regression. among 6983 patients taking warfarin,recruited from 45 countries grouped into 7 regions,the mean i-ttr was 55.2% (sd 21.3%) and the median i-ttr was 57.9% (interquartile range 43.0% to 70.6%). the mean time with inr <2 was 29.1% and the mean time with an inr >3 was 15.7%. while multiple clinical features were associated with i-ttr,dominant determinants were previous warfarin use (mean i-ttr of 61.1% for warfarin-experienced versus 47.4% in vka-naïve patients) and geographic region where patients were managed (mean i-ttr varied from 64.1% to 35.9%). these effects persisted in multivariable analysis. regions with the lowest i-ttrs had inr distributions shifted toward lower inr values and had longer inter-inr test intervals. independent of patient clinical features,the regional location of medical care is a dominant determinant of variation in i-ttr in global studies of warfarin. regional differences in mean i-ttr are heavily influenced by subtherapeutic inr values and are associated with reduced frequency of inr testing. url: clinicaltrials.gov. unique identifier: nct00403767.