Impact of Co-morbidities and Patient Characteristics on International Normalized Ratio Control Over Time in Patients With Nonvalvular Atrial Fibrillation




This study determined the association between co-morbidities, including heart failure (HF) and time in therapeutic range (TTR), in patients with nonvalvular atrial fibrillation. Longitudinal patient-level anticoagulation management records collected from 2006 to 2010 were analyzed. Adult patients with nonvalvular atrial fibrillation who used warfarin for a 12-month period with no gap of >60 days between visits were identified. TTR <55% was defined as “lower” TTR. CHADS 2 score of ≥2 was defined as “higher” CHADS 2 . Logistic regression analyses were conducted to determine the association between co-morbidities and TTR. A total of 23,425 patients met the study criteria. The mean age ± SD was 74.8 ± 9.7 years, with 84.8% aged ≥65 years. The most common co-morbidities were hypertension (41.7%), diabetes (24.1%), HF (11.7%), and previous stroke (11.1%). The mean TTR ± SD was 67.3 ± 14.4%, with 18.6% of patients in the lower TTR range. In multivariate analyses using age, gender, hypertension, diabetes, stroke, and region as covariates, HF (adjusted odds ratio [OR] 1.41, 95% confidence interval [CI] 1.28 to 1.56; p <0.001), diabetes (OR 1.28, 95% CI 1.19 to 1.38; p <0.001), and previous stroke (OR 1.15, 95% CI 1.04 to 1.27; p <0.001) were associated with lower TTR. In a second set of multivariate analyses using gender and region as covariates, a higher CHADS 2 score was associated with lower TTR (OR 1.11, 95% CI 1.04 to 1.18; p <0.001). In conclusion, HF was associated with the greatest likelihood of a lower TTR, followed by diabetes, then stroke. Anticoagulation control may be more challenging for patients with these conditions.


Until recently, vitamin K antagonists such as warfarin were the only efficacious oral anticoagulants available for the prevention of embolic events in patients with nonvalvular atrial fibrillation (NVAF) at high risk of stroke. For most patients on long-term warfarin therapy, an international normalized ratio (INR) of 2.0 to 3.0 is the recommended range for prevention of stroke and systemic embolism ; this level of anticoagulation has been shown to translate to improved outcomes in patients with NVAF. Time spent in therapeutic range (TTR), a measure used to describe the quality of INR control in clinical practice, also correlates with improved patient outcomes. Thus, characterizing TTR and the variables that can influence it, may be helpful in identifying challenges to optimal anticoagulation and improving anticoagulation strategies. The present analysis sought to determine the association among co-morbidities, patient characteristics, and TTR in patients with NVAF whose INR was managed by anticoagulation clinics in the United States.


Methods


This study used longitudinal patient-level anticoagulation management records collected from 2006 to 2010 by the decision support software CoagClinic (Standing Stone, Inc., Westport, Connecticut). This software is used by a large number of institutions (mostly hospital-based) in 49 states. As of December 2010, this system contained data on ∼400,000 patients; this is the largest database of patients receiving anticoagulation therapy.


Because the data were intended to be used for clinical purposes, the International Classification of Diseases 9th Revision, Clinical Modification codes used for medical claims were not included. Therefore, all the data fields were converted into International Classification of Diseases 9th Revision, Clinical Modification format to extract co-morbidity information.


Adult patients with NVAF who used warfarin for ≥1 year with no gap of >60 days between anticoagulation clinic visits were identified; this criterion is in alignment with standard clinical practice, in which regular weekly, bimonthly, or monthly visits are recommended. Subjects with valvular atrial fibrillation were excluded. TTR was calculated according to the Rosendaal method, which uses linear interpolation to assign an INR value to each day between successive observed INR values. This approach, which assumes that INR is gradually increasing or decreasing between measurements, will produce a percentage of days when the INR measurements are within a prespecified range. TTR was calculated for interpolated INR values within the recommended therapeutic range of 2.0 to 3.0.


Two sets of independent logistic regression analyses were conducted. The first set was conducted to determine the association between TTR and co-morbidities, including heart failure (HF), hypertension, diabetes, and previous stroke. “Lower” TTR was defined as <55%. The second set was conducted to determine the association between TTR and CHADS 2 score—a cumulative point-based scoring system. We used CHADS 2 scoring rather than CHA 2 DS 2 -VASc, as it is more widely used in the United States despite CHA 2 DS 2 -VASc being more inclusive in Europe, and it is stipulated as the primary approach for stratifying stroke risk in patients with NVAF in the most current American College of Chest Physicians guidelines.


The CHADS 2 system assigns 1 point for each of the following: presence of HF, presence of hypertension, age ≥75 years, and presence of diabetes. Two points are assigned for a history of stroke or a transient ischemic attack. In the present study, a “higher” CHADS 2 score was defined as ≥2.


Sensitivity analyses were conducted using TTR cut-off points at 45%, 50%, 55%, 60%, 65%, and 70% to determine the impact of different definitions of low and high TTR on the relation between CHADS 2 scores and TTR.




Results


A total of 23,425 patients met the study criteria. Patients had a mean age of 74.8 ± 9.7 years, with 84.8% aged ≥65 years. More than 1/2 (53.9%) of patients had a CHADS 2 score <2. Patient demographics are listed in Table 1 .



Table 1

Patient demographic and baseline characteristics











































































Characteristic Total, n = 23,425 (%)
Age (yrs)
18 to <65 3,572 (15.3)
65 to <75 6,432 (27.5)
≥75 13,421 (57.3)
Women 10,864 (46.4)
Men 12,556 (53.6)
CHADS 2 score
0 3,890 (16.6)
1 8,736 (37.3)
2 6,403 (27.3)
3 2,841 (12.1)
4 1,154 (4.9)
5 346 (1.5)
6 55 (0.2)
Co-morbidities
Heart failure 2,733 (11.7)
Hypertension 9,765 (41.7)
Diabetes mellitus 5,636 (24.1)
Previous stroke 2,593 (11.1)
United States region
Northeast 6,447 (27.5)
Midwest 6,673 (28.5)
West 4,385 (18.7)
South 4,965 (21.2)


The most common co-morbidities were hypertension, diabetes, HF, and previous stroke. The mean TTR ± SD was 67.3 ± 14.4%, with 18.6% of patients in the lower TTR range. Using age, gender, hypertension, diabetes, stroke, and region as covariates, multivariate analysis ( Table 2 ) revealed that increased risk for having a lower TTR was significantly and independently associated with HF, diabetes, and previous stroke. Patients in the Western and Southern regions of the United States were significantly more likely to have lower TTR values than those in the Northeast region ( Table 2 ). Male patients had a lower likelihood of having a lower TTR ( Table 2 ); conversely, female patients were at an increased risk for having lower TTR values. Neither older age (≥75 years) nor location in the Midwest (as compared with the Northeast) was independently associated with the likelihood of lower TTR in this analysis.



Table 2

Impact of demographics and co-morbidities on likelihood of lower time in therapeutic range






















































Characteristic OR (95% CI) p
Age ≥75 (vs <75) (yrs) 0.94 (0.88–1.01) NS
Men (vs women) 0.78 (0.73–0.83) <0.001
United States region
Northeast 1.00 (Referent)
West 1.39 (1.26–1.54) <0.001
South 1.38 (1.26–1.52) <0.001
Midwest 1.04 (0.95–1.14) NS
Co-morbidities (vs not present)
Heart failure 1.41 (1.28–1.56) <0.001
Diabetes 1.28 (1.19–1.38) <0.001
Previous stroke 1.15 (1.04–1.27) 0.0075
Hypertension 0.86 (0.80–0.93) <0.001

CI = confidence interval; OR = odds ratio.


A negative correlation between CHADS 2 scores and TTR is shown in Figure 1 ; the highest CHADS 2 score, 6, was associated with the lowest TTR. In the second multivariate analysis using gender and region as covariates ( Table 3 ), a higher CHADS 2 score, defined as ≥2, was significantly associated with a lower TTR. As in the first multivariate analysis, patients in the Western and Southern regions of the United States were significantly more likely to have lower TTR values than those in the Northeast region ( Table 3 ). Male patients also continued to have a lower likelihood of having a lower TTR compared with female patients ( Table 3 ).




Figure 1


The relation between TTR and CHADS 2 score (0 to 6).


Table 3

Impact of CHADS 2 score on likelihood of lower time in therapeutic range




































Characteristic OR (95% CI) p
CHADS 2 score ≥2 (vs <2) 1.11 (1.04–1.18) 0.003
Men (vs women) 0.80 (0.75–0.85) <0.001
United States region
Northeast 1.00 (Referent)
West 1.43 (1.29–1.58) <0.001
South 1.39 (1.27–1.53) <0.001
Midwest 1.06 (0.96–1.16) NS

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Dec 5, 2016 | Posted by in CARDIOLOGY | Comments Off on Impact of Co-morbidities and Patient Characteristics on International Normalized Ratio Control Over Time in Patients With Nonvalvular Atrial Fibrillation

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