How to Calculate Time in Therapeutic Range (TTR)
The recommended method for calculating TTR is the Rosendaal method of linear interpolation between consecutive INR values, which is the validated standard for assessing anticoagulation quality in patients on warfarin. 1
The Rosendaal Method
The Rosendaal method calculates TTR by performing linear interpolation between two consecutive INR measurements to estimate the INR value for each day between measurements. 1
Key Technical Points:
- Linear interpolation assumes the INR changes at a constant rate between two measured values 1
- INR measurements separated by >42 days should not be interpolated due to large uncertainties in INR fluctuation during extended intervals 1
- The method calculates the proportion of days (expressed as a percentage) when the interpolated INR falls within the target therapeutic range 1
Target INR Range
- The therapeutic INR range for most indications (atrial fibrillation, venous thromboembolism) is 2.0 to 3.0 1
- For mechanical heart valves, a higher target range of 2.5 to 3.5 may be used 1
Alternative Methods (Not Recommended as Primary)
While other calculation methods exist, they are not equivalent to the Rosendaal method and should not be used interchangeably: 1
- Percentage of INRs within range: Simply counts what proportion of measured INR values fall within the therapeutic range, but ignores the time between measurements 1
- Cross-sectional method: Research shows this produces significantly different TTR values (65.97%) compared to Rosendaal (58.12%) 2
- Traditional method: Yields even lower TTR values (51.55%) with high variability 2
Clinical Significance of TTR
A TTR of ≥65% should be the treatment target to maximize efficacy and safety, though ≥70% is associated with even better outcomes. 1
Outcomes Based on TTR:
- TTR ≥65%: Associated with lower rates of stroke/systemic embolism (HR 2.55 for TTR <65%), all-cause mortality (HR 2.39), and major bleeding (HR 1.54) 1
- TTR <65%: Significantly increases risk of adverse events and may warrant consideration of switching to direct oral anticoagulants 1
Common Pitfalls to Avoid
- Do not use "percentage of INRs in range" interchangeably with TTR - these are highly correlated but mathematically different measures 1
- Avoid interpolating INRs >42 days apart - this introduces excessive uncertainty 1
- Do not rely on single "one-off" INR values to assess anticoagulation quality - TTR over time is the validated performance metric 1
- Adding tolerances (±0.2 or ±0.5 to the INR range) artificially inflates TTR values and distorts the true quality of anticoagulation 2
Practical Implementation
The Rosendaal method is the quality and performance measure of choice for specialized anticoagulation clinics and has been validated to predict adverse events in patients receiving warfarin. 1 Most anticoagulation management software incorporates this calculation method automatically. 1