Warfarin Control Research Articles

Effects of safflower injection on the pharmacodynamics and pharmacokinetics of warfarin in rats

1. Safflower injection (SI) is extracted from Chinese herbal medicine safflower that comprises many active components. Warfarin is a common anticoagulant and has exhibited drug interactions with several herbal products. This study aimed to investigate the effects of SI on pharmacodynamics and pharmacokinetics of warfarin in rats.2. Wistar rats were randomly divided into blank control group, SI group, warfarin control group and SI + warfarin group, respectively. In SI and SI + warfarin groups, rats were injected with SI (1.6 mL/kg/d, i.p.) for 14 days. Warfarin (0.2 mg/kg) was given orally on the eighth day. Saline was given as control. The blood samples were collected at various time points. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. UPLC-MS/MS was used to determine the plasma concentrations of S(R)-warfarin, and the pharmacokinetic parameters were calculated.3. PT, APTT in SI and SI + warfarin rats increased significantly compared with corresponding control rats. The pharmacokinetic parameters including Cmax, t1/2, AUC0-t and AUC0-∞ of S-warfarin and R-warfarin in SI + warfarin rats were higher than those in warfarin control rats.4. These findings suggest that SI significantly increases the anticoagulant effect of warfarin by affecting its pharmacodynamic and pharmacokinetic parameters.

Outcomes associated with warfarin time in therapeutic range among US veterans with nonvalvular atrial fibrillation

Background: Poor quality of warfarin control (time in therapeutic range [TTR] < 65%) can lead to increased risk of adverse events. The objective of this study was to examine the overall quality of international normalized ratio (INR) control and the association of TTR with clinical outcomes including stroke, major bleeding, and all-cause mortality among US warfarin users.Methods and results: This retrospective observational cohort study utilized the US Veterans Affairs electronic medical records database (VA EMR). Patients with NVAF who newly initiated warfarin from 1 January 2005 to 31 December 2015 were grouped into two cohorts based on TTR <65% or ≥65%. TTR was computed from INR test results. Clinical outcomes assessed were stroke/systemic embolism (SE), hemorrhagic stroke, ischemic stroke, and major bleeding, defined based on hospitalization with those conditions as primary diagnosis, as well as all-cause mortality. Patients were followed from warfarin initiation to the first occurrence of an outcome or censoring. Propensity score weighted time-varying Cox regression was used to evaluate the risk of the clinical events. A total of 127,385 NVAF patients with mean TTR of 51% were included. TTR <65% was observed in 65% of patients. Mean CHA2DS2-VASC score (SD) was 2.9 (1.5) in the low TTR cohort and 2.7 (1.4) in the high TTR cohort. Patients with TTR <65% had a higher risk for any stroke/SE (HR: 1.57; 95% CI: 1.41–1.75), major bleeding (HR: 2.78; 95% CI: 2.55–3.03) and all-cause mortality (HR: 1.73; 95% CI: 1.67–1.79).Conclusions: The observed quality of warfarin control in VA EMR suggests room for improvement given the association with elevated risk of adverse clinical outcomes.

Factors influencing warfarin control in Australia and Singapore

IntroductionWarfarin is widely used for patients with non-valvular atrial fibrillation (NVAF). Variations in warfarin control, as measured by time in therapeutic range (TTR), have been reported across different regions and ethnicities, particularly between Western and Asian countries. However, there is limited data on comparative factors influencing warfarin control in Caucasian and Asian patients. Therefore, the aim of this study was to determine warfarin control and potential factors influencing this in patients with NVAF in Australia and Singapore. MethodsRetrospective data was collected for patients receiving warfarin for January to June 2014 in Australia and Singapore. TTR was calculated for individuals with mean patient TTR used for analysis. Possible influential factors on TTR were analysed including age, gender, concurrent co-morbidities, and concurrent medication. ResultsThe mean TTR was significantly higher in Australia (82%) than Singapore (58%). At both sites, chronic kidney disease significantly lowered this TTR. Further factors influencing control were anaemia and age<60years in Australia, and vascular disease, CHA2DS2-VASc score of 6, and concurrent platelet inhibitor therapy in Singapore. DiscussionWarfarin control was significantly higher in Australia compared to Singapore, however chronic kidney disease reduced control at both sites. The different levels of control in these two countries, together with patient factors further reducing control may impact on anticoagulant choice in these countries with better outcomes from warfarin in Australia compared to Singapore.

Barriers and facilitators to reducing frequent laboratory testing for patients who are stable on warfarin: a mixed methods study of de-implementation in five anticoagulation clinics

BackgroundPatients on chronic warfarin therapy require regular laboratory monitoring to safely manage warfarin. Recent studies have challenged the need for routine monthly blood draws in the most stable warfarin-treated patients, suggesting the safety of less frequent laboratory testing (up to every 12 weeks). De-implementation efforts aim to reduce the use of low-value clinical practices. To explore barriers and facilitators of a de-implementation effort to reduce the use of frequent laboratory tests for patients with stable warfarin management in nurse/pharmacist-run anticoagulation clinics, we performed a mixed-methods study conducted within a state-wide collaborative quality improvement collaborative.MethodsUsing a mixed-methods approach, we conducted post-implementation semi-structured interviews with a total of eight anticoagulation nurse or pharmacist staff members at five participating clinic sites to assess barriers and facilitators to de-implementing frequent international normalized ratio (INR) laboratory testing among patients with stable warfarin control. Interview guides were based on the Tailored Implementation for Chronic Disease (TICD) framework. Informed by interview themes, a survey was developed and administered to all anticoagulation clinical staff (n = 62) about their self-reported utilization of less frequent INR testing and specific barriers to de-implementing the standard (more frequent) INR testing practice.ResultsFrom the interviews, four themes emerged congruent with TICD domains: (1) staff overestimating their actual use of less frequent INR testing (individual health professional factors), (2) barriers to appropriate patient engagement (incentives and resources), (3) broad support for an electronic medical record flag to identify potentially eligible patients (incentives and resources), and (4) the importance of personalized nurse/pharmacist feedback (individual health professional factors). In the survey (65% response rate), staff report offering less frequent INR testing to 56% (46–66%) of eligible patients. Most survey responders (n = 24; 60%) agreed that an eligibility flag in the electronic medical record would be very helpful. Twenty-four (60%) respondents agreed that periodic, personalized feedback on use of less frequent INR testing would also be helpful.ConclusionsLeveraging information system notifications, reducing additional work load burden for participating patients and providers, and providing personalized feedback are strategies that may improve adoption and utilization new policies in anticoagulation clinics that focus on de-implementation.

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.

A performance evaluation of a novel human recombinant tissue factor prothrombin time reagent (Revohem™ PT).

A new prothrombin time reagent (Revohem™ PT) based on recombinant human tissue factor produced by the silkworm-baculovirus expression system was tested. The aim of this study was to compare the performance of the new PT reagent with two widely used routine PT reagents. All testing was performed on a Sysmex CS-5100 coagulometer. Revohem™ PT was tested for imprecision and stability using normal and abnormal lyophilized commercial control plasmas. Comparability was assessed with two widely used reagents: one containing recombinant human tissue factor (Reagent A) and the other a human placental thromboplastin (Reagent B) using a wide range of normal and abnormal plasmas and analyser-specific ISI values. Excellent between-day imprecision was obtained for Revohem™ PT (CV <1.0%) and acceptable open-vial on-board stability over 7days. There was good agreement between methods in samples from patients with liver disease and patients receiving warfarin and no significant differences between methods with increasing INR values. Both recombinant reagents suffered less interference from lupus anticoagulant than the placental thromboplastin. Revohem™ PT had similar sensitivity to reagents A and B for FII, V, VII and X deficiency and demonstrated dose responsiveness to dabigatran, apixaban and rivaroxaban with steeper response curves than the comparison reagents. Revohem™ PT showed comparable or improved performance relative to two widely used reagents and is suitable for use in warfarin control, detection of inherited factor II, V, VII and X deficiency and assessment of liver disease coagulopathy.

Effect of Shuxuetong injection on anticoagulant effect of warfarin in rats

To explore the effect of Shuxuetong injection on the pharmacodynamics and pharmacokinetics of warfarin in rats, and to provide reference for rational drug use. In studies on the single dose of warfarin, Wistar rats were randomly divided into four groups： blank control group(group A), Shuxuetong injection group(group B), warfarin control group(group C), and warfarin+Shuxuetong injection group(group D). In studies on the steady state of warfarin, Wistar rats were randomly divided into warfarin control group(group E) and warfarin+Shuxuetong injection group(group F). To investigate the pharmacodynamic effect of Shuxuetong injection on warfarin, prothrombin time(PT) and activated partial thromboplastin time(APTT) were measured by coagulation analyzer, and international normalized ratio(INR) was calculated. To investigate the pharmacokinetic effect of Shuxuetong injection on warfarin, the blood concentrations of S-warfarin and R-warfarin were determined by UPLC-MS/MS combined with technology of chiral chromatographic column, and the related pharmacokinetic parameters were calculated accordingly. The results on the single dose of warfarin showed that Shuxuetong injection markedly increased PT, INR(P<0.01), and APTT(P<0.05). Meanwhile, when Shuxuetong injection was co-administrated with warfarin, it significantly increased PT, INR(P<0.01), and APTT(P<0.05) as compared with warfarin control group. In addition, increased pharmacokinetic parameters including Cmax, AUC0-t and AUC0-∞, prolonged t1/2, and decreased CL/F were observed for S-warfarin and R-warfarin. The results of the steady state of warfarin suggested that Shuxuetong injection significantly increased PT and INR of warfarin(P<0.01), and elevated the plasma concentrations of S-warfarin and R-warfarin when co-administrated with warfarin. These findings indicated that Shuxuetong injection had anticoagulant effect, and would produce pharmacodynamics synergistic action when it was co-administrated with warfarin. Shuxuetong injection also decelerated the metabolism of warfarin, and resulted in pharmacokinetics interaction. Therefore, Shuxuetong injection could significantly increase anticoagulant effect of warfarin, indicating that the combination use of these two drugs should be refrained in order to avoid the risk of bleeding in clinical application. If they need to be used in combination, special attention should be paid to ensure the safety of patients.

SAMe-TT2R2 predicts quality of anticoagulation in patients with acute venous thromboembolism: The MAQI2 experience.

A high SAMe-TT2R2 score predicted poor warfarin control and adverse events among atrial fibrillation patients. However, the SAMe-TT2R2 score has not been well validated in venous thromboembolism (VTE) patients. A cohort of 1943 warfarin-treated patients with acute VTE was analyzed to correlate the SAMe-TT2R2 score with time in therapeutic range (TTR) and clinical adverse events. A TTR <60% was more frequent among patients with a high (>2) versus low (0-1) SAMe-TT2R2 score (63.4% vs 52.3%, p<0.0001). A high SAMe-TT2R2 score (>2) correlated with increased overall adverse events (7.9 vs 4.5 overall adverse events/100 patient years, p=0.002), driven primarily by increased recurrent VTE rates (4.2 vs 1.5 recurrent VTE/100 patient years, p=0.0003). The SAMe-TT2R2 score had a modest predictive ability for international normalized ratio (INR) quality and adverse clinical events among warfarin-treated VTE patients. The utility of the SAMe-TT2R2 score to guide clinical decision-making remains to be investigated.

Relationship Between Infarct Volume and Prothrombin Time-International Normalized Ratio in Ischemic Stroke Patients With Nonvalvular Atrial Fibrillation.

In Japan, warfarin treatment at prothrombin time-international normalized ratio (PT-INR) of 1.60-2.60 is recommended for elderly patients with nonvalvular atrial fibrillation (NVAF). But it remains unknown whether PT-INR 1.60-1.99 has a similar effect on stroke severity as a value >2.0. The purpose of this study was to clarify the association between infarct volume and PT-INR levels.Methods and Results:The 180 patients (mean age, 76 years [SD, 10 years], 53% male) selected from 429 consecutive ischemic stroke patients admitted within 48 h of onset between 2004 and 2014 with NVAF were included. We classified them into 4 groups according to their PT-INR values on admission: no warfarin (NW), 129 patients; PT-INR <1.60 (poor control: PC), 29 patients; PT-INR 1.60-1.99 (low-intensity control: LC), 14 patients; and PT-INR ≥2.00 (high-intensity control: HC), 8 patients. Median (interquartile range: IQR) of infarct volume was 55 mL (IQR 14-175) in the NW, 42 mL (IQR 27-170) in the PC, 36 mL (IQR 6-130) in the LC, and 11 mL (IQR 0-39) in the HC groups. The infarct volume of the HC group was significantly smaller than in the other 3 groups, but no difference existed between the LC and PC groups or the LC and NW groups. Warfarin control at PT-INR of 1.60-1.99 is not effective for reducing the severity of ischemic stroke in NVAF patients.

Hospital pharmacist intervention improves the quality indicator of warfarin control: A retrospective cohort study.

Background/Aims Our previous study showed that time in therapeutic range (TTR) control of warfarin therapy was negatively affected in non-valvular atrial fibrillation (NVAF) patients with heart failure. This study assesses the effect of intervention by hospital pharmacists on TTR control in Japanese NVAF patients with heart failure. Method This retrospective cohort study included NVAF patients with heart failure admitted and discharged from the cardiovascular internal medicine ward between March 2011 and July 2013. Participants were classified into two groups according to the instructions by hospital pharmacists and physicians (Intervention group) and by physicians only (Usual care group). The primary outcome was TTR. Secondary outcomes were major bleeding and minor bleeding. Results In total, 57 participants (35 males, 22 females; mean age: 69.7 years) were classified into the Intervention (n = 25) and Usual care (n = 32) groups. TTR within-therapeutic range was significantly higher and within sub-therapeutic range was significantly lower in the Intervention than the Usual care group. Major bleeding and minor bleeding were not significantly different between the two groups. Conclusion The intervention of hospital pharmacists with anticoagulation therapy can lead to proper use of warfarin, which can be useful when physicians prescribe warfarin. J. Med. Invest. 64: 266-271, August, 2017.

Abstract 13411: Outcomes Associated With Warfarin Time in Therapeutic Range among Veterans With Nonvalvular Atrial Fibrillation in the US, 2005-2015

Introduction: This study evaluated the relationship between quality of warfarin control and clinical outcomes among US veterans with nonvalvular atrial fibrillation (NVAF). Hypothesis: Poor quality of warfarin control (time in therapeutic range (TTR) &lt;65%) is associated with reduced effectiveness and safety. Methods: Using the US Veterans Affairs electronic medical records database, patients with NVAF who newly initiated warfarin from 1/1/2005-12/31/2015 were grouped into two cohorts based on TTR &lt;65% or ≥65%. TTR was computed from international normalized ratio test results comprehensively recorded in the database. Clinical outcomes assessed in the study were stroke/systemic embolism (SE), hemorrhagic stroke, ischemic stroke, and major bleeding, defined based on hospitalization with those conditions as primary diagnosis, as well as all-cause mortality. Patients were followed from warfarin initiation to the first occurrence of an outcome or censoring. For each outcome, unadjusted and adjusted hazard ratios (HR and aHR) between two cohorts were estimated, with the latter from propensity score weighting-adjusted time-varying Cox proportional hazard regression stratified by CHA 2 DS 2 -VAS C score (≥2 or not), controlling for setting of warfarin initiation, baseline patient demographic and clinical characteristics, and use of co-medications. Results: A total of 127,385 patients with NVAF (mean age (SD): 71.3 (9.8) years, 99% male) with a median of 1.4 follow-up years (IQR: 3.3) were included. Mean TTR was 51%. TTR&lt;65% was observed in 65% of patients. Mean CHA 2 DS 2 -VAS C score (SD) was 2.9 (1.5) in low TTR cohort and 2.7 (1.4) in high TTR cohort. Low TTR cohort (with mean TTR as 38%) had significantly higher risk for assessed outcomes compared with high TTR cohort (with mean TTR as 77%) (Table). Conclusions: In the study, the observed quality of warfarin control among US veterans with NVAF was suboptimal and associated with elevated risk of adverse clinical outcomes.

The Sex, Age, Medical History, Treatment, Tobacco Use, Race Risk (SAMe TT2R2) Score Predicts Warfarin Control in a Singaporean Population

Warfarin reduces stroke risk in atrial fibrillation (AF) patients but requires ongoing monitoring. Time in therapeutic range (TTR) is used as a measure of warfarin control, with a TTR less than 60% associated with adverse patient outcomes. The Sex, Age, Medical history, Treatment, Tobacco use, Race (SAMe-TT2R2) score has been identified as a model able to predict warfarin control, but this has been tested in mainly Caucasian populations. Therefore, the aim of this study was to determine the ability of the SAMe-TT2R2 score to predict warfarin control in a Singaporean population consisting of Chinese, Malay, and Indian race. Retrospective data were collected from the National Heart Centre Singapore for AF patients receiving warfarin between January and June 2014. The TTR and the SAMe-TT2R2 score were calculated for each patient. The 1137 non-valvular AF patients had a mean TTR of 58.0 ± 34.3% and a median SAMe-TT2R2 score of 3. The categorized SAMe-TT2R2 scores (2 versus >2) showed a significant reduction in mean TTR for the entire population (63.2% versus 55.8%, P = .0004) and also when categorized according to race for Chinese (62.7% versus 56.9%, P = .0075) and Malay (68.4% versus 50.6%, P = .0131) populations. The SAMe-TT2R2 tool is effective in predicting warfarin control in a Singaporean population as patients with a score greater than 2 had poor control. The minimum score for non-Caucasian patients is 2; thus, in these patients, the presence of any additional risk factors identified in the SAMe-TT2R2 tool categorizes them as unlikely to achieve adequate warfarin control and possible candidates for alternative anticoagulants.

The Use of Fish Oil with Warfarin Does Not Significantly Affect either the International Normalised Ratio or Incidence of Adverse Events in Patients with Atrial Fibrillation and Deep Vein Thrombosis: A Retrospective Study.

Background: Warfarin is a leading anticoagulant in the management of atrial fibrillation (AF) and deep vein thrombosis (DVT). Drug interactions influence the safety of warfarin use and while extensive literature exists regarding the effect on warfarin control and bleeding incidence with many medicines, there is little evidence on the influence of complementary medicines. The aim of this study was to assess the influence of fish and krill oil supplementation on warfarin control and bleeding incidence in AF and DVT patients. Methods: A retrospective analysis was conducted utilising patient information from a large private pathology clinic. AF and DVT patients receiving long-term warfarin therapy (>30 days) at the clinic and taking fish and krill oil supplements were eligible for study inclusion. Results: Of the 2081 patients assessed, a total of 573 warfarin users met the inclusion criteria with 145 patients in the fish and krill oil group (supplement group) and 428 patients in the control group. Overall, it was found that fish and krill oils did not significantly alter warfarin time in therapeutic range (TTR) or bleeding incidence, even when compared by gender. Conclusion: Omega-3 supplementation with fish and krill oil does not significantly affect long-term warfarin control and bleeding and thromboembolic events when consumed concurrently in patients managed at an anticoagulation clinic.

Quality of warfarin control in atrial fibrillation patients in South East Queensland, Australia.

Warfarin is widely prescribed to decrease the risk of stroke in atrial fibrillation (AF) patients. Due to patient variability in response, regular monitoring is required, and time in therapeutic range (TTR) used to indicate quality of warfarin control with a TTR>60% is recommended. Recently, an Australian Government review of anticoagulants identified the need to establish current warfarin control and determine the potential place of the newer oral anticoagulants. To determine warfarin control by a pathology practice in Queensland, Australia and identify factors influencing TTR. Retrospective data were collected from Sullivan Nicolaides Pathology, a major pathology practice offering a warfarin care programme in Australia. Patients enrolled in their programme as of September 2014 were included in the study. TTR was calculated using INR test results, and test dates using the Rosendaal method with mean patient TTR were used for analysis and comparison. Exclusions were target therapeutic range outside 2.0-3.0, less than two INR tests and programme treatment time of less than 30 days. The eligible 3692 AF patients had 73.6% of INR tests within the therapeutic range. The mean TTR was 81%, with 97% of patients above a TTR of 60%. TTR was not significantly influenced by age, gender or socioeconomic factors. The observed mean TTR of over 80% is superior to the minimum recommended threshold of 60%. The TTR achieved by the Queensland pathology practice demonstrates that dedicated warfarin programmes can produce high-quality warfarin care, ensuring the full benefit of warfarin for Australian patients.

How to Invest in Getting Cost-effective Technologies into Practice? A Framework for Value of Implementation Analysis Applied to Novel Oral Anticoagulants.

Cost-effective interventions are often implemented slowly and suboptimally in clinical practice. In such situations, a range of implementation activities may be considered to increase uptake. A framework is proposed to use cost-effectiveness analysis to inform decisions on how best to invest in implementation activities. This framework addresses 2 key issues: 1) how to account for changes in utilization in the future in the absence of implementation activities; and 2) how to prioritize implementation efforts between subgroups. A case study demonstrates the framework's application: novel oral anticoagulants (NOACs) for the prevention of stroke in the National Health Service in England and Wales. The results suggest that there is value in additional implementation activities to improve uptake of NOACs, particularly in targeting patients with average or poor warfarin control. At a cost-effectiveness threshold of £20,000 per quality-adjusted life-year (QALY) gained, additional investment in an educational activity that increases the utilization of NOACs by 5% in all patients currently taking warfarin generates an additional 254 QALYs, compared with 973 QALYs in the subgroup with average to poor warfarin control. However, greater value could be achieved with higher uptake of anticoagulation more generally: switching 5% of patients who are potentially eligible for anticoagulation but are currently receiving no treatment or are using aspirin would generate an additional 4990 QALYs. This work can help health services make decisions on investment at different points of the care pathway or across disease areas in a manner consistent with the value assessment of new interventions.

Adequate Initial Heparin Dosage for Atrial Fibrillation Ablation in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants.

Background and ObjectiveDuring atrial fibrillation ablation, heparin is required and is guided by the activated clotting time (ACT). Differences in the ACT before ablation and adequate initial heparin dosing in patients receiving non-vitamin K antagonist oral anticoagulants (NOACs) were examined.MethodsPatients who received warfarin (control, N = 90), dabigatran etexilate (N = 90), rivaroxaban (N = 90) and apixaban (N = 90) were studied. A 100 U/kg dose of heparin was administered as a reliable control dose for warfarin, and the remaining patients were randomly administered 110, 120 or 130 U/kg of heparin in each NOAC group, followed by a continuous heparin infusion.ResultsPeriprocedural thromboembolic and major bleeding were not observed. Minor bleeding occurred rarely without significant differences among the groups examined. Baseline ACTs were longer in the warfarin (152 ± 16 s) and dabigatran (153 ± 13 s) groups than in the rivaroxaban (134 ± 13 s) and apixaban (133 ± 20 s) groups. The initial bolus heparin dosages required to produce an ACT 15 min after the initial bolus that was identical to the control (333 ± 32 s) were 120 U/kg (318 ± 29 s) and 130 U/kg (339 ± 43 s) for dabigatran, 130 U/kg (314 ± 31 s) for rivaroxaban and 130 U/kg (317 ± 39 s) for apixaban. The NOAC groups required significantly larger doses of total heparin than the warfarin group.ConclusionThe baseline ACTs differed among the three NOAC groups. The results of the comparison with warfarin (the control) indicated that dosages of 120 or 130 U/kg for dabigatran, and 130 U/kg for rivaroxaban and apixaban, were adequate initial heparin dosages.

Adequate time in therapeutic INR range using triple antithrombotic therapy is not associated with long-term cardiovascular events and major bleeding complications after drug-eluting stent implantation

BackgroundTriple antithrombotic therapy increases the risk of bleeding events in patients undergoing percutaneous coronary intervention (PCI) compared with dual anti-platelet therapy (DAPT). However, whether warfarin control is associated with reduced cardiovascular events and major bleeding events in patients undergoing PCI with triple antithrombotic therapy is uncertain. MethodsWe investigated 1207 consecutive patients who underwent PCI between 2004 and 2011. Major bleeding complications and major adverse cardiac and cerebrovascular events (MACCE) defined as all-cause death, acute coronary syndrome, target vessel revascularization, and stroke were compared between groups of patients who received either triple antithrombotic therapy or DAPT. ResultsTriple antithrombotic therapy was administered to 95 (7.9%) patients. The mean international normalized ratio of prothrombin time (PT-INR) was 1.8. The target PT-INR level was set between 1.6 and 2.6 and the ratio (%) of time in the therapeutic range (TTR) was calculated. The median TTR was 78.4% (interquartile range, 67.4–87.6%). Kaplan–Meier survival curves showed that warfarin therapy was not associated with MACCE (p=0.89) and major bleeding (p=0.80). Multivariable Cox regression analysis revealed that triple antithrombotic therapy was not an independent predictor of MACCE and major bleeding. ConclusionsTriple antithrombotic therapy does not increase the occurrence of MACCE and major bleeding complications, if the warfarin dose is tightly controlled with a lower INR.

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—

Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. The treatment of VTE is undergoing tremendous changes with the introduction of the new direct oral anticoagulants and clinicians need to understand new treatment paradigms. This article, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. Well-managed warfarin therapy remains an important anticoagulant option and it is hoped that anticoagulation providers will find the guidance contained in this article increases their ability to achieve optimal outcomes for their patients with VTE Pivotal practical questions pertaining to this topic were developed by consensus of the authors and were derived from evidence-based consensus statements whenever possible. The medical literature was reviewed and summarized using guidance statements that reflect the consensus opinion(s) of all authors and the endorsement of the Anticoagulation Forum’s Board of Directors. In an effort to provide practical and implementable information about VTE and its treatment, guidance statements pertaining to choosing good candidates for warfarin therapy, warfarin initiation, optimizing warfarin control, invasive procedure management, excessive anticoagulation, subtherapeutic anticoagulation, drug interactions, switching between anticoagulants, and care transitions are provided.

Prothrombin time on admission in patients with cardioembolic stroke and intracranial hemorrhage occurring during warfarin treatment in the direct oral anticoagulant era.

Warfarin is used worldwide to prevent cardioembolic stroke (CES) in patients with atrial fibrillation even in the era of direct oral anticoagulant (DOAC). We evaluated clinical characteristics of the patients with CES and intracerebral hemorrhage (ICH) occurring during warfarin treatment, focusing on prothrombin time-international normalized ratio (PT-INR) at the occurrence. The consecutive 846 CES patients (78 ± 9 years) and 870 ICH patients (68 ± 13 years) admitted to the Hirosaki Stroke and Rehabilitation Center from April 2011 through March 2015 were studied. The antithrombotic agents administered in CES patients before the onset included antiplatelets in 146 patients (17%), warfarin in 205 (24%), DOAC in 37 (5%), and none in the other 458 (54%). Mean PT-INR within 24 hours after the onset in nonvalvular atrial fibrillation patients with warfarin was 1.34 ± 0.33 (n = 129), and 111 of them (86%) showed PT-INR value below the recommended therapeutic range in Japan. The antithrombotic agents administered in ICH patient included antiplatelets in 87 patients (10%), warfarin in 86 (10%), DOAC in 8 (1%), and none in the other 689 (79%). Mean PT-INR within 24 hours after the onset in patients with warfarin was 2.27 ± 0.62 (n = 65), and 56 of them (86%) showed PT-INR < 2.8. Thus, there is a large population with poor warfarin control complicating CES and that with good warfarin control complicating ICH, indicating limitation of warfarin treatment in the DOAC era.