Warfarin Control In Patients Research Articles

Association Between Warfarin Control Metrics and Atrial Fibrillation Outcomes in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation

Bleeding and thrombotic events (eg, stroke and systemic embolism) are common in patients with atrial fibrillation (AF) taking warfarin sodium despite a well-established therapeutic range. To evaluate whether history of therapeutic warfarin control in patients with AF is independently associated with subsequent bleeding or thrombotic events. In this multicenter cohort study of 176 primary care, cardiology, and electrophysiology clinics in the United States, data were obtained during 51 830 visits among 10 137 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry; 5545 patients treated with warfarin were included in the bleeding analysis, and 5635 patients were included in the thrombotic event analysis. Patient follow-up was performed from June 29, 2010, to November 30, 2014. Data analysis was performed from August 4, 2016, to February 15, 2019. Multiple measures of warfarin control within the preceding 6 months were analyzed: time in therapeutic range of 2.0 to 3.0, most recent international normalized ratio (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. Association of INR measures, alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the subsequent 6 months was assessed post hoc using logistic regression models. A total of 5545 patients (mean [SD] age, 74.5 [9.8] years; 3184 [57.4%] male) with AF were included in the major bleeding analysis and 5635 patients (mean [SD] age, 74.5 [9.8] years; 3236 [57.4%] male) in the thrombotic event analysis. During a median follow-up of 1.5 years (interquartile range, 1.0-2.5 years), there were 339 major bleeds (6.1%) and 51 strokes (0.9%). Multiple metrics of warfarin control were individually associated with subsequent bleeding. After adjustment for clinical bleeding risk, 3 measures-time in therapeutic range (per 1-SD increase ≤55: adjusted odds ratio [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)-remained associated with bleeding risk. Adding INR variance to a clinical risk model slightly increased the C statistic from 0.68 to 0.69 and had a net reclassification improvement index of 0.028 (95% CI, -0.029 to 0.067). No INR measures were associated with subsequent stroke risk. Three metrics of prior warfarin control were associated with bleeding risk but only marginally more so than traditional clinical factors. This study did not identify any measures of INR control that were significantly associated with stroke risk.

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.

Warfarin control in patients transitioning to warfarin after non-vitamin K oral anticoagulant (NOAC) therapy.

Warfarin has long been the most widely prescribed oral anticoagulant. Introduction of non-vitamin K oral anticoagulants (NOACs) has provided anticoagulant options but also presented the potential challenge of transitioning between agents. Changes from NOACs to warfarin are particularly problematic with delays to therapeutic effect and limited real-world data regarding the impact on warfarin control. The aim of this study was to investigate the frequency of switching anticoagulants and the effect on warfarin control. Retrospective data was collected for patients at a warfarin program in Queensland Australia who had exited the program for NOACs plus those who had reverted to warfarin. Data included documented reasons for change and International Normalised Ratio (INR) results with time in therapeutic range (TTR) calculated as a measure of warfarin control. Over 5years, a total of 3036 patients ceased warfarin to commence a NOAC but 142 (4.7%) reverted to warfarin. Majority of patients (60.6%) reverted to warfarin within 6months of trialling NOACs with a median of 6days to therapeutic INR. There was no significant difference in warfarin control before changing to NOACs and after reverting to warfarin (mean TTR 75%) but significantly more frequent testing and lower doses were required to achieve this control. Transitions from warfarin to NOACs results in almost a week to therapeutic effect and warfarin therapy may be further complicated by a need for increased frequency of testing. Further studies are required to refine transition strategies particularly from warfarin to NOAC and minimise potential risks to patients.

Heart Failure Severity and Quality of Warfarin Anticoagulation Control (From the WARCEF Trial)

Previous studies in patients with atrial fibrillation showed that a history of heart failure (HF) could negatively impact anticoagulation quality, as measured by the average time in therapeutic range (TTR). Whether additional markers of HF severity are associated with TTR has not been investigated thoroughly. We aimed to examine the potential role of HF severity in the quality of warfarin control in patients with HF with reduced ejection fraction. Data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction Trial were used to investigate the association between TTR and HF severity. Multivariable logistic regression models were used to examine the association of markers of HF severity, including New York Heart Association (NYHA) class, Minnesota Living with HF (MLWHF) score, and frequency of HF hospitalization, with TTR ≥70% (high TTR). We included 1,067 participants (high TTR, N = 413; low TTR, N = 654) in the analysis. In unadjusted analysis, patients with a high TTR were older and less likely to have had strokes or receive other antiplatelet agents. Those patients also had lower NYHA class, better MLWHF scores, greater 6-minute walk distance, and lower frequency of HF hospitalizations. Multivariable analysis showed that NYHA class III and/or IV (Odds ratio [OR] 0.68 [95% confidence intervals [CIs] 0.49 to 0.94]), each 10-point increase in MLWHF score (i.e., worse health-related quality of life) (OR 0.92 [0.86 to 0.99]), and higher number of HF hospitalization per year (OR0.45 [0.30 to 0.67]) were associated with decreased likelihood of having high TTR. In HF patients with systolic dysfunction, NYHA class III and/or IV, poor health-related quality of life, and a higher rate of HF hospitalization were independently associated with suboptimal quality of warfarin anticoagulation control. These results affirm the need to assess the new approaches, such as direct oral anticoagulants, to prevent thromboembolism in this patient population.

Dedicated warfarin care programme results in superior warfarin control in Queensland, Australia.

Warfarin is used to prevent stroke in patients with atrial fibrillation (AF). Ongoing monitoring of International normalised ratio (INR) and time in therapeutic range (TTR) commonly used to assess the quality of warfarin management are required. Anticoagulant clinics have demonstrated improved TTRs, particularly in countries with poorer control in primary care settings. Reported TTR in Australia has been relatively high; so, it is unknown if benefit would be seen from dedicated warfarin clinics in Australia. The aim of this study was to compare the level of warfarin control in patients managed by their general practitioner (GP) and a warfarin care programme (WCP) by Sullivan Nicolaides Pathology. Retrospective data were collected for AF patients enrolled in the warfarin care programme at WCP, and included patients with INR tests available while managed by their GP. INR tests were used to calculate TTR and frequency of testing for the time managed by GP and WCP, with mean data used for analysis and comparison. The eligible 200 warfarin patients had a TTR of 69% with GP management and 82% with WCP management (<.0001). Significant differences were also found between GP and WCP management in the percentage of tests in range, total number of tests and frequency of testing. WCP had a reduced time to repeat test at extremes of INR results. Australian warfarin control was good when managed by either GP or WCP, but WCP management increased TTR by 13%. Dedicated warfarin programmes can improve warfarin control and optimise therapy for patients.

A High HASBLED Score Identifies Poor Warfarin Control in Patients Treated for Non-Valvular Atrial Fibrillation in Australia and Singapore.

Warfarin reduces stroke risk in atrial fibrillation (AF) patients. The quality of warfarin control, measured by time in therapeutic range (TTR), impacts outcome and adverse events. One tool evaluating risk of adverse events and potential warfarin control would simplify risk-benefit assessment of warfarin. Recently, HASBLED was demonstrated effective for this purpose, but this was in well-controlled patients with deep vein thrombosis. HASBLED as a predictor of warfarin control has not been validated in other populations including differing indications, warfarin control levels and ethnicities. The aim of this study was to determine whether HASBLED can predict warfarin control in patients with AF in Australia and Singapore. Retrospective data were collected for patients receiving warfarin between January and June 2014 in Australia and Singapore. Patient data were used to calculate HASBLED at the start and end of the study period. TTR was calculated for each patient, and mean TTR used for analysis to stratified HASBLED scores. Of the 4370 patients, there were 3199 in Australia and 1171 in Singapore with mean TTRs of 82% and 58%, respectively. At the start of the study, a HASBLED score ≥3 predicted significantly lower TTR in Singapore, whilst at the end of the study, this score identified patients with poor control in both Australia and Singapore. A HASBLED score ≥3 in patients treated with warfarin can differentiate significantly lower TTRs in Australian and Singapore patients with AF. HASBLED may assess bleed risk and warfarin control, identifying patients at high risk of poor warfarin outcome requiring additional INR monitoring or alternative anticoagulation.

Assessment of TTR on warfarin control in patients with atrial fibrillation in Suzuka General Hospital—impact of secondary prevention for stroke—

Assessment of TTR on warfarin control in patients with atrial fibrillation in Suzuka General Hospital—impact of secondary prevention for stroke—

Surrogate Marker of Warfarin Control in Patients with Atrial Fiblliration

Surrogate Marker of Warfarin Control in Patients with Atrial Fiblliration

Evaluation of des-γ-carboxy prothrombin as a marker protein of hepatocellular carcinoma

We measured des-gamma-carboxyglutamic acid prothrombin (protein induced by vitamin K absence or antagonist-Factor II: [PIVKA-II]) in plasmas of normal subjects, patients with thrombotic disease, those with hepatic disease including hepatocellular carcinoma, and those with carcinoma of other tissues, and compared the results with results of blood coagulation tests used for the examination of hepatic function. In addition, in the patients with hepatic disease, PIVKA-II and alpha-fetoprotein (AFP) levels were compared. The PIVKA-II level was frequently high in patients with thrombotic disease given warfarin therapy and those with hepatocellular carcinoma. However, in patients with thrombotic disease who were not given warfarin therapy, no significant correlation was seen between the PIVKA-II value and the results of the thrombotest or hepaplastin test, suggesting no association between the PIVKA-II level and the degree of impairment of hepatic function. In 70 patients with hepatocellular carcinoma, the percentage of patients positive for PIVKA-II (greater than or equal to 0.1 micrograms/ml) and those positive for AFP (greater than or equal to 20 ng/ml) were similar (77% and 74%, respectively). Pearson's correlation of coefficient between the PIVKA-II value and the AFP value in the 70 patients was 0.463. However, false-positive rates in patients with hepatic disease other than hepatocellular carcinoma were lower for PIVKA-II. Combined assessment of PIVKA-II and AFP increased positive rates and allowed exclusion of false-positive patients. The plasma PIVKA-II level is suggested to be useful as an indicator of warfarin control in patients with thrombotic disease, as a marker of hepatocellular carcinoma, and is particularly of value when assessed in combination with AFP.