Warfarin Control Metrics Associated with Subsequent Bleeding Risks

July 6, 2019

An analysis that included data on more than 50,000 patients found that multiple metrics of warfarin control were individuals associated with subsequent bleeding.

A recent study has found that among patients with atrial fibrillation (Afib) taking warfarin, clinical risk scores for major bleeding and thrombotic events were more strongly associated with future events than any international normalized ratio (INR) metrics for warfarin.

After examining more data from more than 50,000 investigators determined that past INR variability was associated with future bleeding events but no INR metric was associated with subsequent thrombotic events.

Investigators sought to determine whether metrics of INR control are associated with bleeding and thrombotic events beyond clinical risk scores for patients with Afib taking warfarin sodium. In order to assess the potential association, investigators identified 10,137 patients with Afib from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry.

Of the 10,137 patients included, 5455 patients treated with warfarin were included in the bleeding analysis and 5635 patients were included in the thrombotic event analysis. Patients were excluded if they had a life expectancy less than 6 months or were not capable of at least 2 years of follow-up.

Main exposures within the study were multiple measures of warfarin control within the preceding 6 months were analyzed. Those included time in therapeutic range of 2.0 to 3.0, most recent INR percentage of time that a patient had interpolated INR values less than 2.0 or greater than 3.0, INR variance, INR range, and percentage of INR values in therapeutic range.

The study’s main outcome measures were association of INR measures, whether alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the proceeding 6-month period, which was investigators assessed via a post hoc analysis using regression models. All analyses were performed using SAS statistical software and all P values were 2 sided and P < .05 was considered to be statistically significant.

Of the 5545 patients included in the b leading analysis, the mean age was 74.5 and 57.4% (n=3184) were male. Of the 5635 patients in the thrombotic event analyses, the mean age was 74.5 and 57.4% (n=3236) were male. Patients included in analyses had a medical CHA2DS2-VASc score of 4.0 and median ORBIT-AF bleeding score of 2.0.

During the follow-up period, investigators noted 339 major bleeding events and 51 strokes. After analyses, investigators found that multiple metrics of warfarin control were individually associated with subsequent bleeding.

After performing adjustments for clinical bleeding risk, there was 3 measures that remained associated with bleeding risk. Those measures were time in therapeutic range (aOR, 1.16; 95% CI, 1.02-1.32), variation in INR values (aOR, 1.32; 95% CI, 1.19-1.47), and maximum INR (aOR, 1.20; 95% CI, 1.10-1.31).

Additionally, investigators found that adding INR variance to clinical risk models slightly increased the C statistic from 0.68 to 0.69. No INR measures were associated with subsequent stroke.

Investigators noted several limitations within the analysis. Target INR for patients was not known, the ORBIT-AF may not representative of all practitioners, INR values at the time of bleed or stroke were not known. Only 51 thrombotic events were included in the current ORBIT-AF analysis. Investigators listed multiple other limitations within their study.

This study, titled “Association Between Warfarin Control Metrics and Atrial Fibrillation Outcomes in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation,” is published in JAMA Cardiology.