Target INR Research Articles

Improving warfarin therapy through implementation of a hospital-based pharmacist managed clinic in Jamaica.

Background:Pharmacist managed warfarin clinics can improve the anticoagulation status of non-valvular patients. The first of such services was implemented at the Cornwall Regional Hospital in Jamaica in 2013.Objectives:To assess the anticoagulation control of patients on warfarin therapy over six months in the pharmacist managed warfarin clinic at Cornwall Regional Hospital.Methods:Retrospective docket review for the period January 2014 to December 2016 was done to include data of patients attending routine clinic appointments for at least six months. Age, gender, date of visit, indication for warfarin therapy, warfarin dose and International Normalized Ratio readings were extracted. Percentage time spent in therapeutic range (TTR) was calculated by month for six months using the Rosendaal linear interpolation method. Patient anticoagulation status was categorized as poor (TTR<40%), moderate (TTR=40-64%) or good (TTR≥65%) and anticoagulation status at three months and six months was compared.Results:For the period of assessment, 52 patients were identified; the median age was 58 years and 36 patients were males. Deep vein thrombosis was the main indication for therapy (22 of 52) and median warfarin weekly dose ranged was 15.0-130 mg. At time of recruitment most of the patients were outside the target INR range (43 of 52). Within one month, the median TTR attained was 31% [IQR 62-10]. This significantly improved by second month to 60% [IQR 82-23] (p=0.001). By month three, the proportion of patients in good, moderate and poor anticoagulant status was 19/51, 15/51 and 17/51 respectively, which at six months changed to 23/51, 12/51. 16/51 respectively; thus, although coagulation status improved from month one to three, there was no significant improvement from month three to month six (p=0.31).Conclusions:The pharmacist managed warfarin clinic monitoring services were successful in attaining TTRs >40% and sustaining these values over six months. The services should therefore be encouraged.

International normalized ratio for the guidance of warfarin treatment in elderly patients after cardiac valve replacement.

Thus far, the target value for international normalized ratio (INR) has remained to be determined. The current study aimed to further explore the INR value of the anti-coagulation drug warfarin after cardiac valve replacement. The clinical data of 213 patients who underwent cardiac valve replacement at Linyi Central Hospital (Linyi, China) between January 2010 and May 2013 were retrospectively analyzed. The warfarin dosage, prothrombin time (PT) and INR were compared among patients with hemorrhage or embolism, and those with no complications. A total of 31 cases (14.6%) developed adverse reactions and complications during the medication period, including 21 cases with hemorrhage (9.9%, hemorrhage group) and 10 cases with embolism (4.7%, embolism group), while 182 patients did not (85.4%, normal group). The average dosage of warfarin was 2.0±0.6, 3.1±0.7 and 1.7±0.6 mg/day in the normal, hemorrhage and embolism groups, respectively. The dosage of warfarin, the PT and the INR in the hemorrhage group were all significantly greater than those in the normal group and the embolism group (all P<0.05). INR monitoring is recommended to ensure the safety of the anti-coagulant drug warfarin, but further study is still required to determine a reasonable target INR value.

Resolution of Intractable Leg Ulcers Associated with Antiphospholipid Syndrome (APS) with Prophylactic Dose of Aspirin (ASA) and Enoxaparin: A Case Report

Background: Lower extremity ulcers are one of the most common skin manifestation in patients (pts) with APS, observed in 20-30% of pts. These skin ulcers typically respond poorly to conventional treatment. Although incompletely understood, the pathogenesis of the skin ulcers (and most of the clinical manifestations of APS) appears to be the result of vascular endothelial damage at the microcirculation level, leading to intracapillary thrombosis and focal inflammation. Systemic treatments with immunomodulatory agents such as glucocorticoids, intravenous immunoglobulin (IVIG) and immunosuppressants have been reported to improve outcomes, but typically carry substantial side-effects, and may not be available outside specialized referralcenters. The use of anticoagulation, with or without immunosuppression, in pts with APS and skin ulcers has been reported with variable results. Our group and others have documented an excellent safety profile with the combination of ASA 81 mg orally and enoxaparin 40 mg subcutaneously given to pregnant patients with APS and recurrent pregnancy loss. Patient with APS appear to share similar microcirculatory changes in the organs involved.Methods: Case report.Results: A 72 year-old gentleman was diagnosed with APS in 2000, when he was evaluated for recurrent deep venous thrombosis in the lower extremities, and was found to have a positive lupus anticouagulant serum test. He received anticoagulation with warfarin, with a target International Normalized Ratio (INR) of 2.5-3.5. In 2011, the patient was evaluated for full-thickness ulceration of the bilateral medial distal legs. He had been treated years earlier with venous ablation, and screening for lower extremity arterial insufficiency showed adequate peripheral circulation. The ulcers were treated with moist antimicrobial wound dressings, serial wound debridement, ongoing compression therapy, and a course of skin substitute therapy. After over one year of treatment the ulcers healed. Over the next several years the patient experienced several episodes of re-ulceration of the lower extremity ulcers despite continued use of compression stockings. He was treated in the same fashion, and each episode of re-ulceration required months of therapy to achieve healing. In mid-2017 he developed another episode of re-ulceration. Similar treatment was again initiated, with little improvement over the first several months of therapy. Physical findings and the recalcitrant nature of the ulcers suggested a direct casual relation with his underlying APS. Since our pt was not a candidate for any form of immunosuppression, he was started on daily subcutaneous enoxaparin 1 mg/kg and daily oral ASA 81 mg. A complete healing of the skin ulcers was noted three months after initiation of the above therapy. He continues on this treatment without any side-effects.Conclusion: A multidisciplinary approach allows for a more detailed evaluation of these challenging cases and helps to improve clinical outcomes. DisclosuresNo relevant conflicts of interest to declare.

Replacing PT-INR Monitoring of Warfarin with Fiix-NR in Clinical Practice Reduces Thromboembolism without Increasing Bleeding Despite Reduced Number of Dose Adjustments

Background: Traditional prothrombin time (PT) based international normalized ratio (INR) is often highly variable. Often this is caused by rapid factor VII reductions due to its short (4 hour) half-life. Thus, factor VII variation is an important confounder during vitamin K antagonist (VKA) dosing. Furthermore, prior studies have demonstrated that factor VII reductions only minimally influence the antithrombotic effect and bleeding risk of VKA, the clinical effect depending mainly on controlled reduction of factors II and X. Therefore, ignoring the influence of FVII during VKA monitoring has the potential to simplify management and outcome.The Fiix prothrombin time (Fiix-PT) is a new modified PT that is only affected by reduced factors II and X. The Fiix-PT is not affected by variations in factor VII. Hence, the Fiix normalized ratio (Fiix-NR) fluctuates less than the standard standard PT-INR. In the double-blind randomized clinical Fiix-trial, published in 2015, monitoring of warfarin with with Fiix-PT (Fiix-NR) was compared to standard high time-in-range PT-INR monitoring. Fiix-NR monitoring led to improved time-in-range, reduced testing frequency, reduced dose-adjustment need and a 50% reduction in thromboembolism (TE). Bleeding did not increase and it occurred at a low rate in both trial arms. Subsequently starting on July 1st 2015 we replaced the PT-INR with Fiix-NR in our anticoagulation monitoring practice.Aim: We compared anticoagulation outcome and dosing frequency during 12 months prior to switching from PT-INR based management (Pre-Fiix monitoring period) and during 12 months following switch to Fiix-NR monitoring (Fiix monitoring period).Methods: This is a retrospective before and after study involving unselected patients managed at a single anticoagulation management service at the Landspitali University Hospital in Reykjavik, Iceland. All patients on warfarin during two consecutive twelve month periods were analysed irrespective of indication or anticoagulation target range. Pre-Fiix patients analysis was based on events occuring during months -12 to -1 before replacing the PT with Fiix PT and the Fiix patients´outcome was analysed during months +4 to +15. Three transitional months were excluded. All patients were dosed by specialized staff using the DAWN anticoagulation software®. Hospital chart diagnostic codes were reviewed for occurrence of TE or major bleeding (MB) during the two separate monitoring periods.Surrogate assessments included the number of tests, testing intervals and dose adjustment frequencies and will be analyzed later.Results: During the Pre-Fiix period 2,345 patients were managed with PT-INR for 1,984 patient years (0.85 years/patient) and during the Fiix period 1,909 patients were managed with Fiix-NR for 1,643 patient years (0.86 y/pt). Indications for warfarin were identical during both periods (atrial fibrillation 57%, venous thromboembolism 26%, prosthetic heart valves 5% and other 12%). The INR target range during both periods was 2.0-3.0 in 92% and 2.5-3.5 in 6%. Clinical outcome with respect to TE and MB is shown in the figure. Overall the point estimates were suggestive of a 34-52% reduction of TE with Fiix-NR monitoring whereas major bleeding was similar. The reduction in untoward events in the Fiix group was statistically significant for composite new TE (OR 0.63;0.41-0.97) and total stroke (ischemic and hemorrhagic, OR 0.57;CI 0.33-0.98), mainly driven by reduced cerebral infarction. Intracranial bleeding occurred in 0.76% in the Pre-Fiix group and in 0.37% in the Fiix montoring group (n.s., OR 0.51;0.19-1.32). The median time-within-Target-range (TTR, Rosendaal method) was similar in both groups (75 vs 76%, respectively), despite dose adjustment frequency being reduced by 18% in the Fiix monitoring group (OR 0.82;CI 0.79-0.85, p <0.0001).Conclusions: These results are in agreement with the results of the Fiix-trial and show that ignoring factor VII during VKA monitoring is safe and leads to reduction in thromboembolism without increasing bleeding. Although TTR was identical in both groups, the dose adjustment need was reduced possibly indicating that less anticoagulation variability in the Fiix-NR group explains reduced thromboembolism. [Display omitted] DisclosuresGudmundsdottir:Hart Biologicals Ltd: Consultancy, Patents & Royalties: Hart Biologicals Ltd is commercializing the Fiix-PT which will be ready for marketing in Europe in the beginning of year 2019 and possibly later that year in the USA. Patent fees will be paid to Fiix Diagnostics Ltd once the test is commercialized.; Fiix Diagnostics Ltd: Equity Ownership, Patents & Royalties: The Fiix prothrombin time (Fiix-PT) is a patented invention of P. T. Onundarson and B.R. Gudmundsdottir that is owned by Fiix Diagnostics Ltd, a start-up company founded by the inventors. . Onundarson:Hart Biologicals Ltd: Consultancy, Other: Hart Biologicals Ltd is commercializing the Fiix-PT which will be ready for marketing in Europe in the beginning of year 2019 and possibly later that year in the USA. Patent fees will be paid to Fiix Diagnostics Ltd once the test is commercialized.; Fiix Diagnostics Ltd: Equity Ownership, Patents & Royalties: The Fiix prothrombin time (Fiix-PT) is a patented invention of P. T. Onundarson and B.R. Gudmundsdottir that is owned by Fiix Diagnostics Ltd, a start-up company founded by the inventors. .

Fatal warfarin-associated intracranial hemorrhage in atrial fibrillation inpatients.

Ischemic stroke and major bleeding, mostly due to intracranial hemorrhage (ICH), cause about the same rates of death in pivotal randomized trials of direct oral anticoagulants (DOACs) versus warfarin for stroke prevention in atrial fibrillation (AF). We analyzed our AF inpatient database to determine whether any ICH-related deaths were potentially preventable. Among 5008 patients admitted to our institution between May 2008 and September 2014 with a diagnosis of AF, eight had fatal ICH between admission and 90days follow-up. The mean age of these patients was 85 years; 62% were male. Localization of the ICH was intraparenchymal in 62% and subdural in 38%. CHA2DS2-VASc scores ranged from 4 to 7, and the HAS-BLED scores ranged from 3 to 7. Three of the eight fatal ICHs were directly due to falls. All 8 patients were taking warfarin. One was taking concomitant aspirin. At the time ICH was diagnosed, one patient had an INR of 5.4. Five patients had an INR within the target therapeutic range of 2.0-3.0, and two had an INR less than 2.0. After multivariate adjustment, a history of falls was the sole independent predictor of fatal ICH (OR 22.3; 95% CI 2.5-60.3). In conclusion, most patients had achieved the target INR at the time of ICH, and the primary precipitant of fatal ICH was often a fall. Using DOACs instead of warfarin and implementing structured fall-prevention programs in high-risk patients could further reduce mortality from ICH in AF.

RF16 EARLY ASPIRIN NON-RESPONDERS IDENTIFICATION BY ROUTINE USE OF AGGREGOMETRY TEST IN LVAD (LEFT VENTRICLE ASSIST DEVICE) PATIENTS REDUCES THE RISK OF PUMP THROMBOSIS.

Introduction: LVAD management is really challenging since inadequate anticoagulation treatment can lead to life threatening sistuations like ischemic stroke or pump thrombosis. Main intention of our study was to investigate if early identification of aspirin non responders can improve anticoagulation management and then reduce the risk of pump thrombosis. Methods: From december 2010 to may 2018 24 patients were implanted with HM II, 6 received an HVAD and 22 an HM 3. A target INR of 2.0 to 3.0 was maintained in all the patients. 100 mg aspirin were initiated only when a normal platelet function emerged at basal postoperative aggregometry. Aspirin non responders were early identified by repeating the aggregometry after seven days of administration and then clopidogrel 75 mg was used and platelet function tested again. Ticlopidine 250 mg was administrated when also clopidogrel was unsuccessful. Results: 6 patients required modification in antiplatelet therapy. 3 patients (5%), 2 HVAD and 1 HM II, suffered from pump thromosis. 1 patient died as a consequence of large intracranial hemorragic event following thrombolitic treatment. 1 patient required pump exchange and in 1 patient thrombolitic infusion was conducted successfully. Conclusions: reported rates of pump thrombosis at 12 months for patients implanted with commonly used LVADs are 6 % to 12 % for axial - flow pumps and 8 % with centrifugal - flow devices. in our serie the reported 5 % overall incidence of pump thrombosis encourage the routine use of aggregometry test to early identify aspirin non responders.

Circannual variations in the international normalized ratio (INR) among mechanical heart valve surgery patients on life-long warfarin

The aim of our study was to explore if there exists a circannual rhythm in INR as fluctuations in anti-coagulation can have serious consequences in patients with mechanical heart valve prosthesis. This is a retrospective study performed in patients with stable INR value for at least 30 days post heart valve surgery in the period 2015–2016 attending a nurse-managed, cardiologist-supervised anti-coagulation clinic at King Abdul Aziz Cardiac Center.we determined average seasonal INR values for each patient, separately for aortic and mitral valve replacement patients. Data were analyzed using JMP Version 7.1, p < 0.05 considered significant. Results are expressed as mean ± SEM, differences between means were analyzed using Wilcoxon-rank sums test and chi-square as appropriate. Seasonal changes in INR were analyzed using analysis of variance of repeated measures (MANOVA), adjusting for potential confounders. Data Collected for 397 patients (mean age 50 ± 0.7 years, 56% male) with a total of 6,220 INRs; 4149 in the high target (2.5–3.5) and 2021 in the low target (2–3) patients. There was no significant difference in the number of INR determinations performed across seasons. INR decreased significantly with time, from the highest value in the summer at 2.8 ± 0.07 to lowest in winter at 2.6 ± 0.02 (p < 0.0001), irrespective of the target INR (p = 0.36). There was no significant interaction between time-related changes in INR and age, gender, INR target, renal impairment, concomitant anti-platelet treatment except for smoking, which showed a significant interaction with INR variation over time (p < 0.001). To the best of our knowledge. This is the first study in the Middle-East extending European and North-American data on circannual changes in INR. Our results confirm the existence of such a rhythm; however the mechanism is unknown. Our findings recognize winter as a challenging season for maintaining optimum anti-coagulation, possibly requiring higher number of outpatient visits and INR determinations, with implications for health care costs.

Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome

Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anti-cardiolipin, and anti-β2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272.

Time in Therapeutic Range and Disease Outcomes in Elderly Japanese Patients With Nonvalvular Atrial Fibrillation.

The relationship between warfarin treatment quality and prognosis for Japanese patients with nonvalvular atrial fibrillation (NVAF) has not been studied thoroughly. Methods and Results: Data from the J-RHYTHM Registry were used to determine the time in therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time in elderly patients (≥70 years). Target INR was 1.6-2.6. Of 7,406 patients with NVAF in the database, 3,832 elderly patients (mean [±SD] age 77.0±5.0 years) constituted the study group. Of these patients, 459 did not receive warfarin and 3,373 received warfarin. Patients on warfarin were subdivided into 4 TTR groups: <40%, 40-59.9%, 60-79.9%, and ≥80%. During the 2-year follow-up, the incidence of thromboembolism and all-cause death was lower in patients with higher TTR (Ptrend<0.001); however, the incidence of major hemorrhage was higher in patients with TTR <40%. In multivariate analysis, compared with the no-warfarin group, TTR 60-79.9% and ≥80% were associated with lower thromboembolic risk, with hazard ratios (HR) of 0.34 (95% confidence interval [CI] 0.17-0.67; P=0.002) and 0.35 (95% CI 0.18-0.68; P=0.002), respectively, and lower all-cause death (HR 0.37 [95% CI 0.22-0.65; P<0.001] and 0.43 [95% CI 0.26-0.71; P=0.001], respectively). TTR <40% was associated with major hemorrhage (HR 5.57; 95% CI 2.04-15.25; P=0.001). In elderly Japanese patients with NVAF, TTR should be maintained ≥60% to prevent thromboembolism and all-cause death. TTR <40% should be avoided to prevent major hemorrhage.

An assessment of knowledge, attitude and practices (KAP) towards warfarin medication among patients with prosthetic valve in a tertiary care hospital of south India

Background: Warfarin is a drug with narrow therapeutic index. It requires varied adequate doses for achieving target INR so as to prevent episodes of thromboembolism. It is important to properly educate the patient while prescribing this drug to reduce the side effects and maintain perfect anticoagulation status. This study was done to assess the baseline Knowledge, Attitude and Practices (KAP) towards warfarin medication among patients with cardiac valve replacement in a tertiary care hospital of south India to get a baseline data which can recommend implementation of health education programs targeting these patients.Methods: An observational cross-sectional study was approved by Institute Ethics Committee JIPMER, Puducherry. It included patients on treatment with warfarin maintenance therapy for a period of not less than three months following cardiac valve replacement in the months of October 2016 to October 2017. The questionnaire included 39 questions of qualitative and quantitative basis, which was scored for a total of 50 and analysed using SPSS software.Results: About 240 patients were interviewed who attended cardiothoracic vascular surgery outpatient department and taking warfarin for at least 3 months following surgery of valve replacement. Patients were divided into two groups. Group A included patients who achieved target INR and group B are those out of target INR. 15.7 percent (35) had low score, 76.2 (160) had medium score and 15 (7.1) percent had high scores in group A. In group B 22(81.5%) had medium score and 5 (18.5%) had high score. The median score was more among patients with higher education (p=0.01). There was no significant difference between scores between different age groups or profession.Conclusions: Lack of adequate knowledge exists in patients who are followed in CTVS OPD when assessed about the basic nature of their disease and drug use. It has been shown that group B had more score which may be due to more education they may have received owing to non-attainment of target INR. This study acts as a baseline and thus advocates the need of proper patient education for patients taking warfarin which may improve the treatment outcome.

Design and rationale of a randomised controlled trial comparing apixaban to phenprocoumon in patients with atrial fibrillation on chronic haemodialysis: the AXADIA-AFNET 8 study

IntroductionPatients with end-stage kidney disease requiring maintenance haemodialysis treatment experience a dramatic cardiovascular morbidity and mortality. Due to the high atherosclerotic and arteriosclerotic burden and profound alterations in haemostasis, they...

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.

Comparison of warfarin dosage fluctuation with time in therapeutic range for bleeding or thromboembolism rate in Chinese patients

Warfarin treatment benefits vary with the clinical skill of warfarin dosage adjustment. However, optimal dosage adjustment in response to the out-of-range international normalized ratio (INR) is not completely understood. Data for 2014-2016 from an integrated health care information system of a single hospital were analyzed. Based on their warfarin dosage fluctuation (WDF), defined as the standard deviation of all prescribed warfarin dosages divided by the mean dosage, the patients were classified into Groups 1 (0-0.10), 2 (0.10-0.20), and 3 (>0.20). Target and in-range INRs were 2.0-2.5 and 1.5-3.0, respectively. Based on time in therapeutic range (TTR), patients were also categorized into Groups 1 (<0.6), 2 (0.6-0.9), and 3 (>0.9). The primary outcome was emergency department visits for bleeding or thromboembolism (TE) events. Eighty-three events were retrieved from 17,397 records (1834 patients). Annual incidence rates were 0.9%, 2.5%, and 4.5% for WDF Groups 1, 2, and 3, respectively (p<0.05), and 2.3%, 1.7%, and 1.7% for TTR Groups 1, 2, and 3, respectively (p=0.41). Area under the receiver operator characteristic curves for WDF and TTR were 0.686 and 0.519, respectively, indicating that WDF exhibited superior predictive performance than TTR. High WDF rather than low TTR was associated with increased bleeding and TE incidence rates.

Clinical Outcomes of Telemonitoring for Patients on Warfarin after Discharge from Hospital.

Objective To evaluate the impact of telephone follow-up service on clinical outcomes in patients on warfarin when discharged from hospital. Methods This randomized controlled trial was conducted at a general hospital in Thailand. Patients aged ≥20 years who were prescribed warfarin when discharged were eligible to participate in this study. They were randomly allocated, using a computer generated random number, to receive either telephone follow-up intervention or usual care. Participants in the intervention group received telephone follow-up by hospital pharmacists for three months. During each telephone call, pharmacists performed medicine use reviews and addressed any problems identified. Key Findings A total of 50 patients participated in this study. The proportion of international normalized ratio (INR) values in the target range for the telephone follow-up group (36/79, 45.6%) was higher than that in the usual care group (19/79, 24.1%), p=0.005. The mean time in the therapeutic range (TTR) in the telephone follow-up group was also higher than that in the usual care group (49.8±34.3 versus 28.0±27.5, p=0.017). All patients in the usual care group experienced one or more out-of-range INR values (25/25, 100%) compared to 21 out of 25 (84%) in the telephone follow-up group, p=0.037. There was no difference between the two groups in the incidence of complications or adverse events associated with warfarin. Conclusions The telephone follow-up service in recently discharged patients helps them achieve and maintain their INR target. This anticoagulant supportive service should be promoted to patients receiving warfarin therapy after discharge. This trial is registered with TCTR20180614006 (Thai Clinical Trials Registry).

Comparisons of Methods and Outcomes of Warfarin Guideline-based Management in Patients on Warfarin Therapy whose International Normalized Ratio (INR) is Higher than Target INR at Vachiraphuket Hospital

Objective: To compare the methods and management outcomes based on the warfarin guidelines of VachiraphuketHospital in patients receiving warfarin whose international normalized ratio (INR) is higher than target INR at Vachiraphuket Hospital.Material and Methods: Retrospective analytic studies were conducted. The data were collected from retrospectiveoutpatient medical records from 1st January 2012-9th September 2016.Results: Sixty-seven patients with a total number of 178 events of INR higher than the target were reported. All events were divided into 84 events and 94 events which dealt and did not deal with the management method according to the warfarin guidelines of Vachiraphuket Hospital, respectively. After treating patients based on the hospital management guidelines, 33 events (39.3%) achieved target INR and 51 events (60.7%) were out of the target INR range. In the cases of patients who were not treated based on the hospital guidelines, 39 events (41.5%) were in the target INR and 55 events (58.5%) were out of INR range. Comparing the management methods and their outcomes, there was no statistically significant difference in achieving target INR between the patients treated with the hospital guideline-based method or the non-guideline-based method (odds ratio=0.913, p-value=0.765).Conclusion: According to the warfarin guidelines of Vachiraphuket Hospital, the management for patients with INR higher than target INR was probably unsuccessful for everyone. Therefore, the management of each individual patient should be carefully considered.

351TAFI level dynamics during long-term warfarin therapy as a predictor of recurrent bleedings in a target INR

351TAFI level dynamics during long-term warfarin therapy as a predictor of recurrent bleedings in a target INR

The Effect of Demographic Factors and VKORC1 1639 G>A Genotypes on Estimated Warfarin Maintenance Dose in Iranian Patients Under Warfarin Therapy.

Warfarin is an anticoagulant that inhibits vitamin K-dependent clotting factors including factor (F) II, FVII, FIX and FX. Different factors can change the effect of this anticoagulant in clinic. Therefore we assessed impact of VKORC1 -1639 G>A polymorphism and demographic factors on required maintenance dose in Iranian patients under warfarin therapy. The study population included 95 patients with a mean age of 61.3 ± 12.6years. Target INR range of 2-3 was considered for these patients. The frequency of VKORC1 -1639 G>A polymorphism was assessed by polymerase chain reaction-restriction length polymorphism(PCR-RFLP). Finally the obtain data were analyzed by SPSS software. Our study revealed that 30.5%, 49.5%, and 20% of the patients had VKORC1 (G/G), (G/A), and (A/A) genotypes, respectively. Carriers of VKORC1 G/G genotype required a higher warfarin dose as compared to A/A carriers (4.48 ± 1.32 and 2.7 ± 1.16mg/day, respectively; P < 0.01). In addition, patients with higher age required lower warfarin therapeutic dose (r = - 0.3, P < 0.01). It seems that -1639 G>A polymorphism and demographic variables had significant effects on warfarin maintenance dose in Iranian patients under warfarin therapy.

A dedicated anticoagulation clinic does not improve postoperative management of warfarin after total joint arthroplasty.

BackgroundPeriprosthetic joint infections (PJIs) are devastating complications. Excessive anticoagulation with warfarin is an independent risk factor for PJIs. The use of a dedicated anticoagulation clinic to improve warfarin management has not been proven.MethodsBetween 2006 and 2014, we identified 92 patients who were placed on postoperative warfarin, and later developed PJI. These patients were compared to 313 patients who underwent total joint arthroplasty placed on warfarin without developing PJI. Patients were included if they had no history of a venous thromboembolic event, were warfarin naive, and enrolled in the anticoagulation clinic. A univariate analysis compared independent variables, and statistical analysis was performed using Student's t-test and Pearson chi-square test for continuous and categorical variables.ResultsThirty-six PJI patients and 297 control patients met the inclusion criteria. The venous thromboembolism rate was 2.1%. At discharge, 82% of all patients were subtherapeutic. Patients were within their target international normalized ratio (INR) range 26.7% of the time. The mean INR in the initial postoperative period for the PJI group was 1.46 and 1.29 in the control group (P < .001). In the acute postoperative period, 13.3% of the knee PJI group were therapeutic or supratherapeutic compared with 3.5% in the knee control group (P = .002).ConclusionsDespite utilization of a dedicated anticoagulation clinic, patients were only within their target INR range 27% of the time. Total knee arthroplasty patients who developed a PJI were more likely to be therapeutic or supratherapeutic in the initial postoperative period. Consequently, the risks associated with warfarin as a venous thromboembolism prophylaxis may outweigh the potential benefits.

Clinically relevant bleeding in cancer patients treated for venous thromboembolism from the CATCH study

Background Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have an increased bleeding risk. Objectives We performed a prespecified secondary analysis of the randomized, open-label, Phase III CATCH trial (NCT01130025) to assess the rate and sites of and the risk factors for clinically relevant bleeding (CRB). Patients/Methods Patients with active cancer and acute, symptomatic VTE received either tinzaparin 175IUkg-1 once daily or warfarin (target International Normalized Ratio [INR] of 2.0-3.0) for 6months. Fisher's exact test was used to screen prespecified clinical risk factors; those identified as being significantly associated with an increased risk of CRB then underwent competing risk regression analysis of time to first CRB. Results Among 900 randomized patients, 138 (15.3%) had 180 CRB events. CRB occurred in 60 patients (81 events) in the tinzaparin group and in 78 patients (99 events) in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.45-0.89). Common bleeding sites were gastrointestinal (36.7%; n=66), genitourinary (22.8%; n=41), and nasal (10.0%; n=18). In multivariate analysis, the risk of CRB increased with age >75years (HR1.83, 95% CI 1.14-2.94) and intracranial malignancy (HR 1.97, 95% CI 1.07-3.62). In the warfarin group, 40.4% of CRB events occurred in patients with with an INR of <3.0. A lower time in therapeutic range was associated with a higher risk of CRB. Conclusions CRB is a frequent complication in cancer patients with VTE during anticoagulant treatment, and is associated with age >75years and intracranial malignancy.

Late clinical outcomes after mechanical aortic valve replacement for aortic stenosis: old versus new prostheses.

The study aimed to evaluate the late clinical outcomes of new-generation mechanical valves for severe aortic stenosis (AS) compared with old mechanical valves. We retrospectively reviewed data from 254 patients with severe AS, who underwent primary mechanical aortic valve replacement from 1995 to 2013. Patients were classified into two groups: old-valve group (n=65: 33 ATS standard, 32 Medtronic-Hall) and new-valve group (n=189: 113 St. Jude Regent, 46 On-X, 30 Sorin Overline). Median patient age was 58 years (Q1-Q3: 52-61). With propensity score matching based on demographic information, 56 patients in the old-valve group were matched with 177 patients in the new-valve group. The median follow-up duration was 91 months (Q1-Q3: 48-138). Cardiac-related mortality and hemorrhagic events were significantly lower in the new-valve group (P=0.047 and P=0.032, respectively). The median international normalized ratio (INR) at follow-up was significantly higher in the old-valve group [2.23, Q1-Q3: 2.14-2.35 (old-valve group); 2.08, Q1-Q3: 1.92-2.23 (new-valve group), P<0.001]. The incidence of prosthesis-patient mismatch (PPM) was significantly higher in the old-valve group (P<0.001). Multivariate analysis of the total population revealed that PPM was a significant risk factor for cardiac-related events [hazard ratio (HR) =5.279, 95% CI, 1.886-14.561, P=0.002] and showed higher trend of increasing mortality (HR =3.082, P=0.076). New mechanical prostheses showed a better hemodynamic performance and lower incidence of PPM. Anticoagulation strategy to lower the target INR in patients with new mechanical valves may improve late outcomes by reducing hemorrhagic events.