Whether warfarin is taken in the morning or the evening makes no meaningful difference in time in therapeutic range

Reference

Garrison SR, Green L, Kolber MR, et al. The effect of warfarin administration time on anticoagulation stability (INRange): a pragmatic randomized controlled trial. Ann Fam Med 2020;18(1):42-49.

Synopsis

Warfarin is typically administered at the end of the day to shorten the interval between international normalized ratio results and dosing adjustments. To figure out if there was anything more than pragmatism guiding this practice, these researchers conducted a trial in real world primary care settings in western Canada. They randomized patients who take warfarin in the evening (with at least 3 months of monitoring data and no immediate plans to stop) to either morning administration (n = 109) or continued evening administration (n = 108). Although patients knew what intervention they received (by the way, this could have been easily fixed by providing placebo doses), the outcome evaluators did not. At baseline, patients in each group spent 72% of their time in the therapeutic range (a bit higher than the 67% typically found). After 7 months, there were no significant departures from baseline trends in time in the therapeutic range. Three patients who took warfarin in the morning had an adverse event (one had gastrointestinal bleeding, one had a thromboembolic stroke, and one had a deep vein thrombosis) compared with 2 in the evening group (one had a thromboembolic stroke, and one had a deep vein thrombosis, an acute arterial occlusion, and a myocardial infarction).