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J Stroke Cerebrovasc Dis. 2015 Oct;24(10):2223-8. doi: 10.1016/j.jstrokecerebrovasdis.2015.05.017. Epub 2015 Jul 29.

International Normalized Ratio Variability: A Measure of Anticoagulation Quality or a Powerful Mortality Predictor.

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CASMU Arrhythmia Service, Montevideo, Uruguay; Department of Cardiology, British Hospital, Montevideo, Uruguay. Electronic address:



As atrial fibrillation (AF) carries twice the mortality hazard when compared with a similar population without diagnosed AF, the importance of risk stratifying is obvious. Several variables are related to outcome: age, comorbidities, and use of several medications, particularly oral anticoagulants. The CHA2DS2VASc score is an extremely useful tool to predict thromboembolic events and also mortality. The international normalized ratio (INR) variability is a treatment efficacy variable also associated with morbidity in patients receiving warfarin. The objective of the study is to compare the prognostic value of the CHA2DS2VASc versus the INR variability or its combination to predict mortality.


In this observational study, we analyzed 589 patients from our Atrial Fibrillation Cohort, all on warfarin for more than 1 year and had more than 5 INRs performed in the last 2 years. The CHA2DS2VASc, HAS-BLED, and SAMe-TT2R2 scores were calculated as well as the INR variability using the time-in-therapeutic-range (TTR), the percentage of INRs (%INRs) within range, and the standard deviation of the INRs (SDINRs). Kaplan-Meier survival curves were plotted via different cutoff points.


The mean TTR was 53 ± 23%; 34.6% of the patients had a TTR above 64%. The mean %INRs in range was 50.2 ± 20.2; 17.3% of the population had %INRs in range above 70%. The mean SDINRs was .84 ± .54, and 38.4% had SDINRs below .79. Of 598, 139 (22%) discontinued warfarin treatment. Death was responsible for almost 50% of treatment discontinuation. Of 598, 68 patients died during the study period (11.5 %); the most frequent causes of death were heart failure (30%), bleeding (17%), and ischemic stroke (15%). Patient survival had a correlation with TTR, %INRs in range, SDINRs, left ventricular ejection fraction, CHA2DS2VASc, and the combination of CHA2DS2VASc + SDINRs (cutoff >1 and >.79, respectively).


INR variability is an extremely useful tool to assess anticoagulation quality. Calculation of both CHA2DS2VASc and INR variability appears to be extremely useful to predict mortality in patients with AF receiving warfarin. The SDINRs emerges as a strong mortality predictor compared to the other INR variability indexes.


Atrial fibrillation; anticoagulants; mortality; therapeutics; warfarin

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