Variability in the Calculation of Time in Therapeutic Range for the Quality Control Measurement of Warfarin

Abstract

Time in therapeutic range (TTR), a well-recognized performance metric of oral anticoagulation, measures the time when patients' international normalized ratios (INRs) are within the desired range. The TTR value can vary significantly depending on the type of method used and can be a skewed indicator of the overall quality of anticoagulation. As such, the present study was designed to compare three methods for TTR calculation (cross-sectional, traditional, and Rosendaal) to quantify their differences, biases, and trends. As part of this investigation, a 21-week retrospective analysis of patients on warfarin was conducted to compare TTR values obtained by these three methods. Paired t-tests, correlation studies between size and bias, and Bland-Altman plots were performed using SAS 9.

Assessment of the quality of anticoagulation management with warfarin in a tertiary care center

“…The TTR has become the most widely accepted and validated method to measure the quality of anticoagulation control and predict adverse events. 8 The Thrombosis Canada Guidelines (2017) state that good INR control is defined arbitrarily as a TTR >60%. 5 The updated chest guidelines and expert panel report (2018) recommend a target TTR ≥70% when adjusting the dose of warfarin to achieve the highest quality of anticoagulation control, and TTRs <65% require therapeutic intervention.…”

TTR: Time in Therapeutic Range or “The Troublesome Report”?

“…Interesting in this respect is an email I received from Fritz Rosendaal himself in June 2017 after he read my editorial in Circulation, 3 in which he stated "I never fully understood why such an absolute meaning has been given to the measure [TTR], which as I am sure you know from our 1993 publication, was not developed for this reason [as a uniform measure of OAC management quality]." Thus, although I agree with the conclusion stated in the Siddiqui et al 1 article that they "recommend a standardized TTR calculation method as well as a uniform tolerance for use in clinical trials and quality control efforts [be developed]," I believe that not only should just one approach to the TTR calculation be used if possible, such as that of Rosendaal et al, 5 but also that additional clinically important information that was used to contribute to the TTR calculation-such as the specifics of the INR values out of range, the number of INR values utilized, and the median INR value present-be provided.…”

“…In the December 2018 issue of the Journal of Innovations in Cardiac Rhythm Management, Saddiqui et al 1 present an interesting discussion regarding comparative approaches in calculating the time in therapeutic range (TTR) measurement, which is the most common metric used to represent the quality of oral anticoagulation (OAC) with vitamin K antagonists (VKAs) such as warfarin. They reported, through the completion of a 21-week retrospective analysis, that the three different methods generally employed in clinical practice and clinical research-specifically, the traditional, cross-sectional, and Rosendaal methods-do not accurately measure whether a patient is in or out of the therapeutic range because there can be inconsistency between their findings for the same patient over the same time period.…”

“…The investigators also noted that the addition of tolerances [ie, small widening of the range by 0.2 and 0.5 at either end beyond the standard 2.0 to 3.0 international normalized ratio (INR)] that has been suggested can further distort the perception of anticoagulation achieved. Moreover, Saddiqui et al 1 recommended that a standardized TTR calculation method as well as a uniform tolerance for use in clinical trials and quality control efforts be implemented.…”

“…Furthermore, perhaps even more troublesome than the above is the fact that the TTR can be misleading to the user, even when its value is considered high-the latter, as Siddiqui et al 1 note, being 50% to 60% in clinical practice or 60% to 69% in clinical research trials. Consider the following: two patients can each have a TTR value of 60% (obtained using the same method to calculate over the same period of time using the same number of measurements).…”