Improving Quality Measurement for Anticoagulation: Adding International Normalized Ratio Variability to Percent Time in Therapeutic Range

Study Questions:

In atrial fibrillation (AF) patients treated with warfarin, is there added predictive ability for adverse events by combining the percent time in therapeutic range (TTR) and the international normalized ratio (INR) variability?


In a group of 40,404 veterans treated with warfarin for stroke prevention in AF patients, TTR and log-transformed INR variability were calculated for each patient. Outcomes measured included ischemic stroke and major bleeding. Cox regression models were performed using TTR and INR variability separately, together, and with an interaction term.


Higher INR variability (unstable control) predicted ischemic strokes (hazard ratio [HR], 1.45; p < 0.001) and major bleeding (HR, 1.57; p < 0.001) independently, regardless of TTR level. The model incorporating an interaction term showed a significantly higher risk for ischemic stroke and major bleeding in high INR variability compared to low INR variability patients at moderate TTR levels (HR, 1.27 and 1.29, respectively) and high TTR levels (HR, 1.55 and HR 1.56, respectively), but not at low TTR levels.


The authors concluded that unstable anticoagulation (as measured by INR variability) predicts adverse events related to anticoagulation independently of TTR. The authors suggest that knowing a patient’s INR variability may help to further risk stratify for adverse events beyond the TTR.


The authors tested an important clinical question and found that INR variability is an independent predictor of adverse events in anticoagulation of AF patients beyond the traditional measure of TTR. Although this analysis was limited to Veterans Administration patients (primarily men) who are managed in anticoagulation clinics, the results are not surprising to anyone who regularly cares for warfarin patients, and likely can be extended to patients treated outside of formal anticoagulation clinics as well. However, both the TTR and the INR variability measures are not available before a patient initiates therapy and therefore are not helpful when deciding between warfarin and a newer target-specific oral anticoagulant (e.g., dabigatran, rivaroxaban, or apixaban). Nonetheless, both of these measures can be useful for large anticoagulation clinics that are implementing quality improvement initiatives to improve the anticoagulation care provided as a means of targeting the most ‘at-risk’ patients.

Clinical Topics: Anticoagulation Management

Keywords: Quality Improvement, Stroke, Veterans, Warfarin, United States Department of Veterans Affairs

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