Time In Therapeutic Range Values Research Articles

SAMe-TT2R2 in tunisian population: Results from the NATURE AF registry

Identifying patients who are likely to achieve and maintain a therapeutic international normalized ratio when prescribed a vitamin K antagonist (VKA) for stroke prevention in atrial fibrillation (AF) is challenging. The SAMe-TT 2 R 2 score was developed on the basis of common clinical factors that can highlight patients who may be unable to achieve and maintain good anticoagulation control. Our objective was to validate this score in a nationwide cohort of non-valvular AF patients. We studied a cohort of consecutive Tunisian patients with non-valvular AF who had oral anticoagulation. The baseline and 6-months SAMe-TT2R2 score was calculated. We included 915 patients, of whom 440 (48.1%) were male. Their median age was 65 years, median Cardiac failure or dysfunction, Hypertension, Age over 75 years [Doubled], Diabetes, Stroke [Doubled] - Vascular disease, Age between 65–74 and Sex category [Female] (CHA2DS2-VASc) score was 2 (0–9), and median Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score was 1 (0–5). The median SAME-TT2R2 score was 2 (0–8). At 12 months, the mean ± standard deviation time in therapeutic range was 48.9% ± 28.7% overall, and 110 patients (12.0%) had a time in therapeutic range value > 65%. Patients with a SAME-TT2R2 score 0 to 1 had a mean time in therapeutic range of 49.3% ± 30.4%, whereas patients with a SAME-TT2R2 score ≥ 2 had a mean time in therapeutic range of 48.7% ± 28.0% ( P 0.871). The odds ratio for having a low time in therapeutic range value was 1 (95% confidence interval, 0.9–1.0; P 0.871) for those patients with a SAME-TT2R2 score ≥ 2. In a “real-world” cohort of patients with atrial fibrillation and oral anticoagulation with VKA, there was no clinical value evidence of the SAME-TT2R2 score for the identification of patients who would have poor-quality anticoagulation.

Quality of anticoagulation with warfarin in rural Chhattisgarh, India

Background & objectives:In most of rural India, warfarin is the only oral anticoagulant available. Among patients taking warfarin, there is a strong association between poor control of the international normalized ratio (INR) and adverse events. This study was aimed to quantify INR control in a secondary healthcare system in rural Chhattisgarh, India.Methods:The INR data were retrospectively obtained from all patients taking warfarin during 2014-2016 at a secondary healthcare system in rural Chhattisgarh, India. Patients attending the clinic had their INR checked at the hospital laboratory and their warfarin dose adjusted by a physician on the same day. The time in therapeutic range (TTR) was calculated for patients who had at least two INR visits.Results:The 249 patients had 2839 INR visits. Their median age was 46 yr, and the median body mass index was 17.7 kg/m2. They lived a median distance of 78 km (2-3 h of travel) from the hospital. The median INR was 1.7 for a target INR of 2.0-3.0 (n=221) and 2.1 for a target of 2.5-3.5 (n=28). The median TTR was 13.0 per cent, and INR was subtherapeutic 66.0 per cent of the time. Distance from the hospital was not correlated with TTR.Interpretation & conclusions:INR values were subtherapeutic two-thirds of the time, and TTR values were poor regardless of distance from the health centre. Future studies should be done to identify interventions to improve INR control.

Variability in the Calculation of Time in Therapeutic Range for the Quality Control Measurement of Warfarin.

Time in therapeutic range (TTR), a well-recognized performance metric of oral anticoagulation, measures the time when patients’ international normalized ratios (INRs) are within the desired range. The TTR value can vary significantly depending on the type of method used and can be a skewed indicator of the overall quality of anticoagulation. As such, the present study was designed to compare three methods for TTR calculation (cross-sectional, traditional, and Rosendaal) to quantify their differences, biases, and trends. As part of this investigation, a 21-week retrospective analysis of patients on warfarin was conducted to compare TTR values obtained by these three methods. Paired t-tests, correlation studies between size and bias, and Bland–Altman plots were performed using SAS 9.4 (SAS Institute, Cary, NC, USA). It was revealed that the TTR values for the cross-sectional, Rosendaal, and traditional methods were 65.97, 58.12, and 51.55, respectively. The addition of tolerances to INR ranges of ± 0.2 and ± 0.5 increased TTR values to 81.79 and 91.53, respectively, for the cross-sectional method, and 66.86 and 82.69, respectively, for the traditional method. The use of the traditional method resulted in significantly higher TTR values than did use of the Rosendaal method, with high variability between the methods in both positive and negative directions. There was a demonstrated lack of independence between the methods, and zero bias could not be assumed. In conclusion, the different methods considered in the present study do not accurately measure whether a patient is in or out of the therapeutic range, and the addition of tolerances can further distort the perception of anticoagulation achieved. We recommend a standardized TTR calculation method as well as a uniform tolerance for use in clinical trials and quality control efforts.

Renal Dysfunction Affects Anticoagulation Control With Warfarin and Outcomes in Japanese Elderly Patients With Non-Valvular Atrial Fibrillation.

It is unclear whether renal dysfunction affects warfarin control in patients with non-valvular atrial fibrillation (NVAF). Methods and Results: Using a dataset from the J-RHYTHM Registry, time in therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time, and creatinine clearance (CrCl) were determined in elderly patients aged ≥70 years. Target INR values were 1.6-2.6 following Japanese guidelines. Incidences of thromboembolism, major hemorrhage, and all-cause death were determined over 2 years. Of 7,406 NVAF patients enrolled in the registry, 2,782 elderly patients (mean age, 75 years) had data for CrCl measured at baseline and TTR. TTR values were lower in the lower CrCl groups (P<0.001 for trend). CrCl <30 mL/min was independently associated with TTR <65% (odds ratio, 1.49; 95% confidence interval, 1.13-1.95; P=0.004). In the multivariate analysis, TTR <65% was independently associated with thromboembolism (hazard ratio, 2.26; 95% confidence interval, 1.37-3.72; P=0.001), but CrCl was not (CrCl <30 mL/min, 1.68, 0.41-6.85, P=0.473). However, CrCl <30 mL/min and TTR <65% were independently associated with all-cause death (5.32, 1.56-18.18, P=0.008 and 1.60, 1.07-2.38, P=0.022, respectively) and the composite event (thromboembolism, major hemorrhage and all-cause death) (2.03, 1.10-3.76, P=0.024 and 1.58, 1.22-2.04, P=0.001, respectively). Elderly NVAF patients with renal dysfunction had poor warfarin control, which was associated with higher risk of thromboembolism and all-cause death.

Impact of provision of time in therapeutic range value on anticoagulation management in atrial fibrillation patients on warfarin

IntroductionThe importance of time in therapeutic range (TTR) in patients prescribed warfarin therapy for stroke prevention in atrial fibrillation (AF) cannot be overemphasised.AimTo evaluate the impact of provision of TTR...

Potential factors affecting the anticoagulation control in patients treated with warfarin: Results WARFARIN-TR study

Background: In the present study, we aimed to evaluate the factors that might be caused by adequate anticoagulation control in patients treated with warfarin for any reason. Methods: The WARFARIN-TR (The Awareness, Efficacy, Safety, and Time in Therapeutic Range of Warfarin in Turkish Population) study included 4987 patients using warfarin between January 1, 2014 and December 31, 2014. Time in therapeutic range (TTR) was calculated according to F. R. Roosendaal's algorithm with linear interpolation. The study population divided into two groups; adequate international normalized ratio (INR) control when TTR ≥70% (Group 1, n = 1068, 21.4%) and inadequate INR control when TTR <70% (Group 2, n = 3919, 78.6%). All demographic and clinic characteristics of the patients were compared to determine possible factors that might be cause adequate warfarin use. Results: The mean age of the study population was 60.7 ± 13.5 years, and there was no significant difference between groups. The mean TTR value of Group 1 was significantly higher than Group 2 (80 ± 8.5 vs. 40.9 ± 17.2; P < 0.001). The traditional cardiovascular risk factors were similar between groups except hypertension (Group 1 51.4% and Group 2 56.4%; P = 0.004) and chronic kidney disease (Group 1 8.3% and Group 2 5.5%; P = 0.001). There were no significant differences between groups regarding bleeding. The awareness of warfarin use was significantly higher in Group 1 patients than Group 2 patients. Multivariate logistic regression analysis revealed that age (odds ratio [OR], 1.007; P = 0.014), hypertension (OR, 0.821; P = 0.01), atrial fibrillation (OR, 1.180; P = 0.033), chronic kidney disease (OR, 1.697; P < 0.001), to know warfarin use reason (OR, 1.699; P < 0.001), and know to food-drug interaction with warfarin (OR, 1.583; P < 0.001) were independent predictors of adequate coagulation. Conclusion: Our study demonstrated that a low proportion of patients taking warfarin achieve an adequate TTR in daily practice. Furthermore, the patients with adequate TTR are more aware of warfarin use.

Quality of oral anticoagulation with vitamin K antagonists in 'real-world' patients with atrial fibrillation: a report from the prospective multicentre FANTASIIA registry.

The efficacy and safety of oral anticoagulation (OAC) using the vitamin K antagonists (VKA) are closely associated with the quality of anticoagulation, reflected by time in therapeutic range (TTR). The SAMe-TT2R2 is a risk score developed to predict the quality of anticoagulation control among VKA users. To analyse the quality of anticoagulation and its clinical determinants based on different methods in a prospective cohort of atrial fibrillation patients on VKA treatment participating in the multicentre Spanish observational registry FANTASIIA. Estimated TTR was calculated from Rosendaal, direct method, international normalized ratio variability, and NICE criteria. Time in therapeutic range values were compared for those patients with a SAMe-TT2R2 score 0-2 and >2. One thousand four hundred and seventy patients were analysed (56.4% male, mean age 74.1 ± 9.5 years). Mean TTR was 61.5 ± 25.1 with Rosendaal and 64.7 ± 24.2 with direct method. There was a high correlation between both methods (ρ = 0.805). The prevalence of poor anticoagulation control was 55%. Diabetes mellitus [odds ratio (OR) 1.38; P = 0.008], peripheral artery disease (PAD, OR 1.62; P = 0.048), and HAS-BLED (OR 1.13; P = 0.022) were independently associated with TTR < 70%. SAMe-TT2R2 score 0-2 had a higher mean TTR than patients with SAMe-TT2R2 >2 (P = 0.044), with a specificity of > 90% for predicting TTR < 70%. Patients with TTR < 70% had higher risk of events (21.7 vs. 16.8%; P = 0.021). In a multicentre prospective registry, 55% of AF patients had poor anticoagulation control with diabetes mellitus, PAD, and HAS-BLED being independently associated with TTR < 70%. A high SAMe-TT2R2 scores had a high specificity for predicting a TTR < 70% as an indicator of poor quality anticoagulation.

The Time in Therapeutic Range and Bleeding Complications of Warfarin in Different Geographic Regions of Turkey: A Subgroup Analysis of WARFARIN-TR Study.

Background: The time in therapeutic range values may vary between different geographical regions of Turkey in patients vitamin K antagonist therapy.Aims: To evaluate the time in therapeutic range percentages, efficacy, safety and awareness of warfarin according to the different geographical regions in patients who participated in the WARFARIN-TR study (The Awareness, Efficacy, Safety and Time in Therapeutic Range of Warfarin in the Turkish population) in Turkey.Study Design: Cross-sectional study.Methods: The WARFARIN-TR study includes 4987 patients using warfarin and involved regular international normalized ratio monitoring between January 1, 2014 and December 31, 2014. Patients attended follow-ups for 12 months. The sample size calculations were analysed according to the density of the regional population and according to Turkish Statistical Institute data. The time in therapeutic range was calculated according to F.R. Roosendaal’s algorithm. Awareness was evaluated based on the patients’ knowledge of the effect of warfarin and food-drug interactions with simple questions developed based on a literature review. Results: The Turkey-wide time in therapeutic range was reported as 49.5%±22.9 in the WARFARIN-TR study. There were statistically significant differences between regions in terms of time in therapeutic range (p<0.001). The highest rate was reported in the Marmara region (54.99%±20.91) and the lowest was in the South-eastern Anatolia region (41.95±24.15) (p<0.001). Bleeding events were most frequently seen in Eastern Anatolia (41.6%), with major bleeding in the Aegean region (5.11%) and South-eastern Anatolia (5.36%). There were statistically significant differences between the regions in terms of awareness (p<0.001).Conclusion: Statistically significant differences were observed in terms of the efficacy, safety and awareness of warfarin therapy according to different geographical regions in Turkey.

Anticoagulation control among patients with nonvalvular atrial fibrillation: A single tertiary cardiac center experience.

There is a limited knowledge about the predictors of anticoagulation control in patients with nonvalvular atrial fibrillation (NVAF). Furthermore, few reports addressed the role of time in therapeutic range (TTR) that could reflect the safety and efficacy of anticoagulation therapy. We aimed to assess factors that affect the quality of anticoagulation therapy utilizing TTR in patients with NVAF. A retrospective observational study was conducted for patients with NVAF who were maintained on warfarin >6 months at a tertiary cardiac care hospital. Patients were categorized according to the TTR status (≥65% vs. <65%). A total of 241 eligible patients were identified. A high-quality anticoagulation based on TTR values ≥65% was found in 157 (65.1%) patients; the remaining (34.9%) patients represented the low-quality anticoagulation group (TTR <65%). Demographics and clinical characteristics were comparable in the two TTR groups. Both groups were comparable in terms of warfarin dose and medications use. When compared to patients with high-quality anticoagulation, patients in the low-quality anticoagulation group were more likely to seek outpatient warfarin clinic visits more frequently (22.3 ± 5.5 vs. 18 ± 4.4, P = 0.001) and to have higher rate of polypharmacy (57.1% vs. 42%, P = 0.03). Of note, patients in both groups had similar major bleeding events (P = 0.41). After adjusting for age and sex, polypharmacy use was a predictor of poor coagulation control (odds ratio = 1.89, 95% confidence interval: 1.03–3.33; P = 0.03). In NVAF patients, TTR is generally high in our cohort. Patients with polypharmacy and frequent clinic visits have lower TTR. High-quality oral anticoagulation could be achieved through optimizing TTR without a significant risk of major bleeding.

Time to Revisit the Time in the Therapeutic Range.

In recent clinical trials, the \"quality\" of warfarin management has been characterized by the time in therapeutic range (TTR) -- with the therapeutic range being an INR between 2.0 and 3.0. In many reviews of recent clinical trials, differences in the TTR have been used comparatively to critique and contrast the trials. However, TTR is a more complex measurement than is commonly appreciated, and many factors that underlie the TTR calculation, which can differ from trial to trial, have not been adequately addressed. This manuscript attempts to explain these issues so as to help the reader understand the factors that contribute to TTR and to understand the limitations of TTR so as to better understand anticoagulation trial results. It also addresses the issue of INRs below or above the therapeutic range, that can differ among trials, that are not provided simply by presenting a TTR value, but that can in a substantial way affect the bleeding risk and embolism-prevention likelihood of anticoagulation in a trial.

Improvement of time in therapeutic range with warfarin by pharmaceutical intervention.

Background Anticoagulation therapy with warfarin is highly effective for prevention and treatment of thromboembolic disorders. Nevertheless, its management is challenging especially in developing countries, where the medical access is difficult and patient education is poor. Objective To determine the effect of pharmaceutical intervention (PI) on the time in therapeutic range (TTR) of a group of anticoagulated patients from our referral center. Method A group of consecutive outpatients previously treated by usual medical care underwent PI. The intervention consisted in the identification and avoidance of food and drug interactions, the confection of medication schedule charts and education to patients regarding side effects and drug monitoring. Mean TTR before and after PI was compared through the Wilcoxon test for repeated measures. Regression analyses were performed to assess the relationship between a TTR level under 65% and potential explanatory variables. Results Mean TTR before PI was 37.4±23.5% and after PI it raised to 67.0±24.9%. Mean change in TTR was +29.5% (95% CI 14.5-44.6; p<0.001). Before PI only 4 patients had TTR values above 65%, in contrast to 18 patients after PI. Conclusion Our findings support the efficacy of PI to improve TTR values in patients treated with warfarin.

Right Ventricular Dysfunction Complicates Time in Therapeutic Range in Heart Failure Patients Receiving Warfarin

Aim: We aimed to evaluate the effect of echocardiographically demonstrated right ventricular dysfunction (RVD) on time in therapeutic range (TTR) in heart failure (HF) patients receiving warfarin therapy. Methods: A total of 893 consecutive HF patients were included and classified into 4 different subgroups: HF with preserved ejection fraction (HFpEF) without RVD (n = 373), HF with reduced EF (HFrEF) without RVD (n = 215), HFpEF with RVD (n = 106) and HFrEF with RVD (n = 199). Groups were compared according to baseline, demographic and clinical data and the characteristics of warfarin therapy. Results: Presence of RVD yielded lower median TTR values both in HFpEF and HFrEF patients. RVD, current smoking, New York Heart Association functional class III/IV, hypertension, diabetes mellitus, pulmonary disease, prior transient ischemic attack or stroke, chronic kidney disease (CKD) stage 4/5 and CKD stage 3 were found to be independent predictors of poor anticoagulation control in multivariate logistic regression analysis. Conclusions: The present study demonstrated that presence of RVD in HF increases the risk for poor anticoagulation.

Determinants of Time in Therapeutic Range in Patients Receiving Oral Anticoagulants (A Substudy of IMPACT)

Implanted cardiac arrhythmia devices can detect atrial tachyarrhythmias (atrial high-rate episodes [AHREs]) that are considered to correlate with atrial fibrillation and risk of stroke. In the IMPACT trial, oral anticoagulation was initiated when AHREs were detected by implanted cardioverter-defibrillators and withdrawn when they abated, according to a protocol accounting both for AHRE duration as detected by remote device monitoring and stroke risk assessment. In this analysis, we ascertained determinants of time in therapeutic range (TTR) among protocol-determined vitamin K antagonist-treated patients during the trial. We enrolled 2,718 patients with at least 1 additional stroke risk factor (CHADS2 score ≥1) at 104 arrhythmia centers. The sex, age <60, medical history, treatments interacting with VKA, tobacco use (2 points) and race (2 points for non-Caucasian) (SAMe-TT2R2) score is a simple clinical-derived score designed to aid decision-making on whether a patient is likely to achieve good anticoagulation control on vitamin K antagonist (e.g., warfarin), which was calculated and related to TTR achieved using the Rosendaal method. We analyzed 229 patients (mean age 66.7years; mean CHADS2 score 2.85 [SD 1.1]) with mean TTR of 0.536 (SD 0.23) overall. Univariate analysis identified 5 variables associated with differences in mean TTR. Mean TTR was lower in those who were women (p= 0.031), of black race (p= 0.005) and in New York Heart Association class IV (p= 0.014), whereas hemoglobin >13.5g/dl (p= 0.010) and New York Heart Association class I (p= 0.037) were associated with higher mean TTR. There was a significant difference in mean TTR value between US and non-US sites (Canada and Germany) (mean TTR for US: 0.513 vs non-US: 0.686; p <0.0001). Mean TTR was significantly lower (Δ= 0.1382, 95% CI 0.0382 to 0.2382) for patients with SAMe-TT2R2 scores of 4 (p= 0.007) and higher (Δ= 0.0612, 95% CI 0.0005 to 0.1219) for patients with SAMe-TT2R2 scores of 1 (p= 0.048). Linear regression confirmed a significant association between lower SAMe-TT2R2 score and improved anticoagulation control (p= 0.0021) with a 1-unit decrease in SAMe-TT2R2 score associated with an increase in TTR of 0.0404 (95% CI 0.0149 to 0.0659). In conclusion, clinical, geographical, and demographic factors were associated with the quality of anticoagulation control as reflected by TTR. Although overall TTR in this population was poor, lower SAMe-TT2R2 scores were associated with better TTR.

Abstract 132: Comparing Time in Therapeutic Range between Point of Care and Tele-Management Patients

Introduction: A strong relationship exists between the Time in Therapeutic Range (TTR), bleeding and thromboembolic events. The TTR percentage can be calculated by the following three methods. The Rosendaal method assumes a linear relationship between two INR values, the Cross Section method uses INR values that are within a specified range and at a specific point in time, and the Fraction of INR Results method measures the number of INRs in a specified range over the total number of INRs. Objectives: Compare the TTR between Point of Care (POC) and Tele-Management (TELE) Non-Valvular Atrial Fibrillation (NVAF) patients calculated by the Rosendaal, Cross Section, and Fraction of INR Results methods. Methods: Data was collected retrospectively during the 2014 calendar year for 100 randomly selected patients ≥ 18 years, received warfarin without interruption, and were monitored by the Penn State Hershey Medical Center Anticoagulation Clinic. INR lab values were obtained 14 days after initiating warfarin therapy and the interval between 2 consecutive INR lab values was ≤ 56 days. All patients in this study had a target INR range of (2.0-3.0). There was a total number of 1,889 INR lab values collected for the POC (n=826) and TELE (n=1,063) cohort groups respectively. The mean TTR value was calculated for each patient. When comparing TTR between the POC and TELE cohorts, the two-sample t-test was used for both the Rosendaal and Fraction of INR Results methods and the Chi-Square test was used for the Cross Section method. Results: Illustrated in Table 1, the mean TTR for the entire study sample (n=100) was (72.4%, 70.0%, and 67.6%) for the Rosendaal, Cross Section, and Fraction of INR Results methods respectively. When comparing between the POC and TELE cohorts, the TTR was 72.8% for the POC cohort and 72.0% for the TELE cohort by the Rosendaal method (p=0.81); the TTR was 64.0% for the POC cohort and 76.0% for the TELE cohort by the Cross Section method (p=0.19); and the TTR was 68.3% for the POC cohort and 67.0% for the TELE cohort by the Fraction of INR Results method (p=0.69). Conclusion: The mean TTR percentage did not provide a consistent pattern among the different TTR calculation methods or between the POC and TELE cohort groups. The differences observed between the POC and TELE cohort groups were not statistically significant (all p &gt; 0.05).

Evaluation of the impact of warfarin time in therapeutic range on outcomes of patients with atrial fibrillation in Turkey: perspectives from the observational, prospective WATER Registry.

Warfarin is highly efficacious in reducing stroke risk in patients with atrial fibrillation (AF). However, its safety and efficacy in stroke prevention is markedly influenced by its time in therapeutic range (TTR). The quality of anticoagulant therapy varies considerably among countries. Representative data concerning the quality of anticoagulant therapy and its effects on clinical outcomes in Turkey are lacking. Warfarin in Therapeutic Range (WATER) registry is a prospective, observational study which followed 572 AF patients (mean age 67.3 ± 12 years; females 60%; 71% non-valvular AF) treated with warfarin. At a median of 22-month follow-up, the mean TTR value was 42.3 ± 18% (median: 40%) for the whole population and lower in non-valvular AF su group than valvular AF subgroup (40.3 ± 18 vs. 46.9 ± 19, respectively, p < 0.001). Death, cardiac hospital-ization and minor bleeding rates were higher in the group with TTR value < 40% than the group with > 40% (3.4% vs. 5.9%; 28.6% vs. 35.4%; 36.5% vs. 41.7%, respectively, all of them p < 0.001). A correlation analysis showed a negative correlation between age and TTR value (r = -0.178, p < 0.001). Mean CHA2DS2VASc score was 3.63 ± 1.5 and mean HASBLED score was 2.38 ± 1.01 in the non-valvular AF group. A negative correlation was observed between TTR levels and CHA2DS2VASc score. WATER provides insight into the anticoagulation control status of AF patients in Turkey. The quality of anticoagulation was poor. Strategies should be undertaken by clinicians and patients to improve TTR. New oral anticoagulant agents may be perfect alternatives for non-valvular AF patients.

The SAMe-TT2R2 Score Predicts Poor Anticoagulation Control in AF Patients: A Prospective ‘Real-world’ Inception Cohort Study

ObjectivesInternational guidelines recommend that an average individual time in therapeutic range should be >65% to 70% for optimal efficacy and safety outcomes while taking a vitamin K antagonist. The Sex, Age (<60 years); Medical history (at least 2 of the following: hypertension, diabetes, coronary artery disease/myocardial infarction, peripheral arterial disease, congestive heart failure, previous stroke, pulmonary disease, hepatic or renal disease); Treatment (interacting drugs, eg, amiodarone for rhythm control) [all 1 point]; and the current Tobacco use (2 points) and Race (non-Caucasian; 2 points) (SAMe-TT2R2) score would help decision making by identifying those patients with newly diagnosed atrial fibrillation who could do well on vitamin K antagonists. The study objective was to validate the predictive value of the SAMe-TT2R2 score for discriminating those who would achieve a high time in the therapeutic range (≥65%) in a prospective “real-world” cohort of patients with atrial fibrillation initiating oral anticoagulation therapy with vitamin K antagonists. MethodsWe studied an inception cohort of consecutive patients with nonvalvular atrial fibrillation who initiated oral anticoagulation in our outpatient anticoagulation clinic. The baseline SAMe-TT2R2 score was calculated. At 6 months, we calculated the time in therapeutic range using a linear method. ResultsWe included 459 patients, of whom 222 (47%) were male. Their median age was 76 years (interquartile range, 70-82 years), median Cardiac failure or dysfunction, Hypertension, Age over 75 years [Doubled], Diabetes, Stroke [Doubled] – Vascular disease, Age between 65-74 and Sex category [Female] (CHA2DS2-VASc) score was 4 (3-5), and median Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score was 3 (2-3). The median SAME-TT2R2 score was 2 (1-2). At 6 months, the mean ± standard deviation time in therapeutic range was 64% ± 17% overall, and 248 patients (54%) had a time in therapeutic range value >65%. Patients with a SAME-TT2R2 score 0 to 1 had a mean time in therapeutic range of 67% ± 18%, whereas patients with a SAME-TT2R2 score ≥2 had a mean time in therapeutic range of 61% ± 16% (P < .001). The odds ratio for having a low time in therapeutic range value was 2.10 (95% confidence interval, 1.44-3.06; P < .001) for those patients with a SAME-TT2R2 score ≥2. ConclusionsIn a prospective “real-world” inception cohort of patients with atrial fibrillation initiating oral anticoagulation with acenocoumarol, we have validated the clinical value of the SAME-TT2R2 score for the identification of patients who would have poor-quality anticoagulation. Thus, rather than imposing a “trial of vitamin K antagonists” for such patients (and exposing such patients to thromboembolic risks), we can a priori identify those patients who can (not cannot) do well on a vitamin K antagonists. Such patients would benefit from additional strategies for improving anticoagulation control with vitamin K antagonists or alternative oral anticoagulant drugs.

Low Dose Oral Vitamin K Does Not Increase Time in Therapeutic Range: Results of a Multicentre Clinical Trial

Warfarin remains the most commonly used oral anticoagulant. Its efficacy is closely correlated with the time in therapeutic range (TTR) of the international normalized ratio (INR). Excellent anticoagulant management systems can achieve TTRs in excess of 80%: however, in day-to-day clinical practice TTR values in the range of 50 to 60% are more commonly seen. Strategies to increase TTR are widely sought; one such intervention is the daily administration of low dose vitamin K (VK) administered to reduce variations in VK intake and thus reduce fluctuations in the INR due to such variability. In this multicentre, blinded, randomized controlled trial we allocated patients on chronic warfarin therapy to receive either 0.150 mg of daily oral VK, or matching placebo. After a one month “run in period” to allow adjustment of the warfarin dose, patients were followed for a maximum of 9 months (mean 6 months), their INR was determined, their TTR calculated and their mean warfarin dose calculated. A total of 253 patients were enrolled at 4 clinical centres between Aug 19, 2010 and Aug 30, 2013; 18 (9 in each group) were excluded from this analysis due to inadequate follow-up data, mostly as a result of withdrawal from the study during the run in period. Of the 117 analyzable patients allocated to VK, 66 were male (average age 66.9 yrs). Of the 118 analyzable patients allocated to placebo 59 were male (average age 65.7 yrs). Indications for warfarin were similar between the two groups, as was the frequency of renal insufficiency and the presence of cancer. Patients allocated to placebo were more likely to report a history of bleeding (7% vs 3%). Mean TTR over the 6 months prior to enrollment to the study was 54.6% in the placebo group, and 51.8% in the VK group. Mean TTR over an average follow-up of 6 months after completion of the 1 month run-in period was 66% in the placebo group, and 65.1% in the VK group. We conclude that inclusion in this study resulted in a statistically (and likely clinically) significant improvement in the TTR. The improvement in the TTR we observed appeared to be predominately as a result of attentive clinical management, rather than administration of VK. Our findings do not support the use of daily, low dose oral vitamin K administered in an effort to improve TTR. DisclosuresCrowther:Portola: Consultancy; Leo: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy; AKP America: Consultancy; Heart and Stroke Foundation: Career Investigator award Other; Celgene: Honoraria; Shire: Honoraria; CSL Behring: Honoraria. Lazo Langer:Pfizer: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; Leo Pharma: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria; Alexion: Research Funding; Daichii Sankyo: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Yeo:Bayer: Honoraria. Schulman:Boehringer Ingelheim: Consultancy, Honoraria, Research Funding; Bayer HealthCare: Consultancy, Honoraria, Research Funding.

Abstract 19108: Anticoagulation Treatment in High-Risk Medicare Advantage Patients with Non-Valvular Atrial Fibrillation

OBJECTIVE: Examine anticoagulation (AC) treatment in Medicare Advantage Prescription Drug (MAPD) plan members diagnosed with non-valvular atrial fibrillation (NVAF) and at high risk for stroke. METHODS: A retrospective analysis of claims data from a large US health plan was conducted. Patients with NVAF were identified between 1/1/2011 and 11/30/2013. Index date was based on NVAF diagnosis and patients were required to have ≥18 months of continuous enrollment: 6 months pre-index and 12 months post-index. Pre-index stroke risk was calculated using the CHADS 2 . Patients classified as high risk (CHADS 2 score ≥2) were included in the analysis. Post-index AC treatment options were warfarin and novel oral anticoagulants (NOACs), dabigatran, apixaban, rivaroxaban. The proportion of high-risk patients with time in therapeutic range (TTR)≥60% was calculated among those receiving warfarin with ≥2 INR values within a 3-month period. Adherence among high-risk patients receiving a NOAC or warfarin without available INR values was calculated using the proportion of days covered (PDC)≥80%. Risk for major bleeding was also calculated using the HASBLED score. Descriptive statistics were used to summarize AC treatment. FINDINGS: Of 93,864 patients with NVAF, 70,646 were identified as high risk for stroke. Among them, 36,601 (51.8%) were treated with an AC while 34,045 (48.1%) did not receive any AC treatment during post-index. Of those treated with an AC, 30,802 (84.2%) were treated with warfarin and 5,799 (15.8%) were treated with a NOAC. TTR was calculated for 7,034 (22.8%) of those receiving warfarin, of which 3,215 (45.7%) had a TTR≥60%. PDC≥80% was observed for 13,758 (57.9%) of the remaining warfarin users and 3,353 (58.7%) of NOAC users. A total of 64,191 (90.8%) patients had a HASBLED score ≥3. CONCLUSIONS: A large proportion of NVAF patients at high risk for stroke are untreated or potentially undertreated_as evidenced by the low TTR values and low adherence estimates observed here. These patients’ high risk levels for stroke and major bleeding necessitate optimal prophylactic treatment with AC and careful management. Further research with providers may identify potential causes for non-treatment and undertreatment with AC in high risk NVAF patients.

Estimation of the impact of warfarin’s time-in-therapeutic range on stroke and major bleeding rates and its influence on the medical cost avoidance associated with novel oral anticoagulant use-learnings from ARISTOTLE, ROCKET-AF, and RE-LY trials

Warfarin's time-in-therapeutic range (TTR) is highly variable among patients with nonvalvular atrial fibrillation (NVAF). The objective of this study was to estimate the impact of variations in wafarin's TTR on rates of stroke/systemic embolism (SSE) and major bleedings among NVAF patients in the ARISTOTLE, ROCKET-AF, and RE-LY trials. Additionally, differences in medical costs for clinical endpoints when novel oral anticoagulants (NOACs) were used instead of warfarin at different TTR values were estimated. Quartile ranges of TTR values and corresponding event rates (%/patient - year = %/py) of SSE and major bleedings among NVAF patients treated with warfarin were estimated from published literature and FDA documents. The associations of SSE and major bleeding rates with TTR values were evaluated by regression analysis and then the calculated regression coefficients were used in analysis of medical cost differences associated with use of each NOAC versus warfarin (2010 costs; US payer perspective) at different TTRs. Each 10 % increase in warfarin's TTR correlated with a -0.32%/py decrease in SSE rate (R(2) = 0.61; p < 0.001). Although, the rate of major bleedings decreased as TTR increased, it was not significant (-0.035%/py, p = 0.63). As warfarin's TTR increased from 30 to 90% the estimated medical cost decreased from -$902 to -$83 for apixaban, from -$506 to +$314 for rivaroxaban, and from -$596 to +$223 for dabigatran. Among NVAF patients there is a significant negative correlation between warfarin's TTR and SSE rate, but not major bleedings. The variations in warfarin's TTR impacted the economic comparison of use of individual NOACs versus warfarin.

Effectiveness of Pharmacy Run Anticoagulation Clinics Compared to Large Clinical Trials of New Oral Anticoagulants

Abstract Purpose: The purpose of the study was to assess the quality of anticoagulation with warfarin in patients with non-valvular AF who were managed exclusively in pharmacy run anticoagulation clinics and to evaluate whether these patients would be expected to have the same efficacy and safety profiles as those patients in the RE-LY, ROCKET AF, and ARISTOTLE trials. Methods: This was a retrospective study of 146 patients in 3 pharmacy run anticoagulation clinics who were initiated on anticoagulation with warfarin therapy to prevent stroke associated with atrial fibrillation. International Normalized Ratio (INR) values were collected over a 1-year period and the quality of management was expressed as time in therapeutic range (TTR) calculated by Rosendaal’s linear interpolation method. Results: Forty-six patients from university internal medicine (UIM) clinic, 9 patients from family medicine (FM) clinic, and 91 patients from pharmacotherapy (PCT) clinic were studied. During the 1-year period, the overall mean TTR was 61.1%. The mean TTR in the UIM clinic, the FM clinic, and the PCT clinic was 60.1%, 62.5%, and 61.5%, respectively. Conclusion: The quality of anticoagulation with warfarin, as assessed by TTR, in the 3 pharmacy run anticoagulation clinics was similar to the mean TTR values reported for the warfarin-treated patients in the RE-LY, ROCKET-AF, and ARISTOTLE trials. The results of these studies are applicable to our patient population.