Therapeutic Range Of Warfarin Research Articles

Review of time in therapeutic range of warfarin in a tertiary centre in Malaysia

Anticoagulation management is a recognized challenge in medical care. Complications of supratherapeutic anticoagulation are hemorrhagic stroke, major bleeding, and death. There is an even greater risk of ischemic stroke in AF, worsening of VTE associated with subtherapeutic dosing.

The Prevalence and Risks of Inappropriate Combination of Aspirin and Warfarin in Clinical Practice: Results From WARFARIN-TR Study

Background:The use of warfarin and aspirin in combination is restricted to limited patients under relevant guidelines.Aims:To evaluate the prevalence of the inappropriate combination of aspirin and warfarin therapy in daily practice and its risks.Study Design:Cross-sectional study.Methods:The awareness, efficacy, safety, and time in the therapeutic range of warfarin in the Turkish population study is a multi-center observational study that includes 4987 patients using warfarin for any reason between January 1, 2014, and December 31, 2014. To determine the prevalence of inappropriate combination use in daily practice, all patients who had a history of atherosclerotic disease (ischemic heart disease, peripheral artery disease) or cerebrovascular disease (n=1498) were excluded. The data of 3489 patients were analyzed. We defined inappropriate combination as all patients who received aspirin and warfarin regardless of the indication for warfarin use, under the direction of the European Society of Cardiology guideline recommendation.Results:The mean age of patients was 59.2±13.8 years (41.8% male). The prevalence of the inappropriate use of warfarin and aspirin combination was 20.0%. The prevalence of combination therapy in patients with a primary indication for mechanical heart valve, non-valvular atrial fibrillation, and other reasons was 20.5%, 18.7%, and 21.0%, respectively. Multivariate logistic regression analysis revealed that age (odds ratio, 1.009; 95% confidence interval, 1.002-1.015; p=0.010), heart failure (odds ratio, 1.765; 95% confidence interval, 1.448-2.151; p<0.001), smoking (odds ratio, 1.762; 95% confidence interval, 1.441-1.153; p<0.010), chronic kidney disease (odds ratio, 2.057; 95% confidence interval, 1.494-2.833; p<0.001), and deep vein thrombosis (odds ratio, 0.463; 95% confidence interval, 0.229-0.718; p=0.001) were independent predictors of combination therapy (r2=0.66). The mean time in therapeutic range of patients receiving combination therapy was significantly lower than in those on warfarin monotherapy (51.6±27.05 vs. 54.7±23.93; p=0.006). Overall, 19.4% (n=677) of patients had a bleeding event (major bleeding 13.0%, n=88) within a year. Percentages of patients with combination therapy were significantly higher in patients with major bleeding than in patients without major bleeding (29.5% vs. 19.7%; p=0.023).Conclusion:Our study demonstrated that 20.0% of patients taking warfarin use concomitant aspirin inappropriately in daily practice. Patients receiving aspirin with warfarin were demonstrated to have more comorbidities, lower time in therapeutic range levels, and higher bleeding rates.

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.

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.

The awareness, efficacy, safety, and time in therapeutic range of warfarin in the Turkish population: WARFARIN-TR.

Objective:The awareness, time in therapeutic range (TTR), and safety of warfarin therapy were investigated in the adult Turkish population.Methods:This multicenter prospective study includes 4987 patients using warfarin and involved regular international normalized ratio (INR) monitoring between January 1, 2014 and December 31, 2014. TTR was calculated according to F.R. Roosendaal’s algorithm. Awareness was evaluated based on the patients’ knowledge of warfarin’s affect and food–drug interactions.Results:The mean TTR of patients was 49.52±22.93%. The patients with hypertension (55.3%), coronary artery disease (23.2%), congestive heart failure (24.5%), or smoking habit (20.8%) had significantly lower TTR levels than the others. Of the total number of patients, 42.6% had a mechanical valve, 38.4% had non-valvular atrial fibrillation (AF), and 19% had other indications for warfarin. Patients with other indications had lower TTR levels than those with mechanical valve and non-valvular AF (p=0.018). Warfarin awareness decreased in higher age groups. The knowledge of warfarin’s food–drug interactions was 55%. People with higher warfarin awareness had higher TTR levels. Patients with ≤8 INR monitoring/year had lower TTR levels (46.4±25.3 vs. 51.1±21.3, respectively, p<0.001) and lower awareness (44.6% vs. 60.6%, p<0.001) than patients with ≥8 INR monitoring/year. In this study, 20.1% of the patients had a bleeding event (major bleeding 15.8%, minor bleeding 84.2%) within a year.Conclusion:Both the mean TTR ratios and awareness of the Turkish population on warfarin therapy were found to be low. It was thought that low TTR levels of the Turkish population may be caused by the low awareness of warfarin, warfarin’s food–drug interactions, and high rates of concomitant diseases. (Anatol J Cardiol 2016; 16: 595-600)

GENDER BASED DIFFERENCES IN BENEFIT FROM NOVEL ORAL ANTICOAGULANT DRUGS COMPARED TO WARFARIN IN ATRIAL FIBRILLATION: AN ANALYSIS OF PUBLISHED STUDIES

Women develop atrial fibrillation at an older age and have a higher risk of stroke than men. Female gender is an independent risk factor for not being in the therapeutic range of warfarin in the recently published SAMe-TT2R2 score. Even within the therapeutic range of warfarin, women remain at

PCV94 - Novel Oral Anticoagulants Versus Warfarin – A Business Case Analysis

The decision on whether to use more expensive novel oral anticoagulants (NOACs) or invest resources for quality improvement of warfarin therapy requires inputs of both clinical and economic outcome analyses. Outcomes of NOACs comparing to warfarin therapy at various levels of patient-time in therapeutic range (TTR) in patients with atrial fibrillation were examined from health care provider’s perspective. A Markov model was designed to compare life-long economic and treatment outcomes of warfarin and NOACs in a hypothetical cohort of 65-year-old atrial fibrillation patients with CHADS2score 2 or above. Model inputs were derived from clinical trials published in literature. Outcome measure was incremental cost per quality-adjusted life-year (QALY) gained (ICER). Expected cost and QALYs of NOACs were USD96,602 and 9.957, correspondingly, in base-case analysis. Using USD50,000 as the threshold of willingness-to-pay per QALY, NOACs therapy was cost-effective when TTR of warfarin therapy was 60%, or monthly cost of warfarin management increased by 1.5-fold or above to achieve 70% TTR. Warfarin therapy was cost-effective when TTR of warfarin was 70% with no increment in monthly cost of care, or when TTR reached 75% with monthly cost of warfarin care increased up to 2.5-fold. At TTR 60%, 70% and 75%, NOACs was cost-effective when monthly drug cost was <USD208, <USD135-200 and <USD96-160, respectively. 10,000 Monte Carlo simulations showed NOACs to be cost-effective in 77.2%, 52.7% and 31.7% of time at TTR of 60%, 70% and 75%, respectively. Acceptance of NOACs as cost-effective was highly depended upon drug cost, anticoagulation control for warfarin, and anticoagulation service cost.

Novel Oral Anticoagulants Versus Warfarin Therapy at Various Levels of Anticoagulation Control in Atrial Fibrillation—A Cost-Effectiveness Analysis

The decision as to whether to use more expensive novel oral anticoagulants (NOACs) or invest resources for quality improvement of warfarin therapy requires input from both clinical and economic analyses. Cost-effectiveness of NOACs compared to warfarin therapy at various levels of patient-time in therapeutic range (TTR) in patients with atrial fibrillation was examined, from the healthcare provider's perspective. A Markov model was used to compare life-long economic and treatment outcomes of warfarin and NOACs in a hypothetical cohort of 65-year-old atrial fibrillation patients with CHADS2 scores of 2 or above. Model inputs were derived from clinical trials published in the literature. The outcome measure was incremental cost per quality-adjusted life-year (QALY) gained (ICER). Using United States Dollar (USD) 50,000 as the threshold of willingness-to-pay per QALY, NOACs therapy was cost-effective when TTR of warfarin therapy was 60 % or below, or monthly cost of warfarin management increased by two-fold or more to achieve 70 % TTR. Warfarin therapy was cost-effective when TTR of warfarin was 70 % with up to a 1.5-fold increment in monthly cost of care, or when TTR reached 75 % with monthly cost of warfarin care increased up to three-fold. At TTR 60 %, 70 % and 75 %, NOACs was cost-effective when monthly drug cost was < USD 200, < USD 122-185 and < USD 85-145, respectively. 10,000 Monte Carlo simulations showed NOACs to be cost-effective 83.6 %, 50.7 % and 32.7 % of the time at TTR of 60 %, 70 % and 75 %, respectively. The acceptance of NOACs as cost-effective was highly dependent upon drug cost, anticoagulation control for warfarin, and anticoagulation service cost.

Prediction of the Bleeding Events in Patients with Atrial Fibrillation

Background: Thromboprophylaxis with oral anticoagulation is most effective in reducing stroke but is associated with similar rates of major bleeding in atrial fibrillation (AF) patients. Recently, the European Society of Cardiology provided a novel bleeding risk score named HAS-BLED. This purpose of this study was to validate the predictive value of HAS-BLED and degree of the activities-of-daily-life (ADL) in patients with AF. Methods and Results: From January 2009 to October 2009, 173 consecutive patients with documented AF by ECG at presentation to the emergency department were enrolled. The ADL were dichotomized (preserved or impaired) by the use of a Katz’ ADL scale (1963). During a mean follow-up period of 12 months, 41 (24%) patients experienced bleeding from any cause. There were no significant differences in the age, sex, prevalence of warfarin or antiplatelet use, or target therapeutic range of warfarin (60%) between the patients with and those without bleeding. The patients with bleeding had higher HAS-BLED scores (4.9±1.5 vs. 3.1±1.4, p=0.01) and more impaired ADL (63% vs. 37%, p=0.02) than those without bleeding. A logistic regression analysis revealed that prediction of bleeding events was improved when impaired ADL was considered with the HAS-BLED score (C-statistic: 0.752 vs. 0.786). Conclusion: Impaired ADL, in addition to the HAS-BLED score, was significantly predictive of bleeding in AF patients.

Evaluation of coagulant activity after mechanical heart valve replacement

Long-term oral anticoagulant therapy is required for recipients of mechanical heart valves. In our hospital, the international normalized ratio of prothrombin time (PT-INR) has been set in the range 1.5-2.5 since October 2001. To evaluate whether coagulant activity is fully suppressed by this target range, coagulant activity was evaluated by measuring thrombin-antithrombin III complex (TAT) levels and valve-related complications were investigated retrospectively. Two hundred twenty-three patients who underwent mechanical valve replacement were enrolled in this study. PT-INR and TAT were measured at our outpatient clinic in March 2005 and valve-related complications since October 2001, when we started to control PT-INR in the range 1.5-2.5, were investigated. Under adequate warfarin control, there was no significant correlation between PT-INR and TAT, however nine patients who exhibited a PT-INR of less than 2.0 had high levels of TAT. And in atrial fibrillation (AF) patients after mitral valve replacement (MVR), the level of TAT was significantly high compared with sinus rhythm patients after atrial valve replacement. Valve-related complications were bleeding events at 2.75% per patient year and thromboembolism at 0.32% per patient year. Attention to complications of thromboembolism is necessary when the PT-INR is less than 2.0, especially in AF patients after MVR and in those with a thrombotic past history or high levels of TAT. The monitoring of TAT is useful in detecting potential coagulation factors and to determine the therapeutic range of warfarin that can normalize coagulant activity.