Anticoagulation Management Service Research Articles

Impact of a pharmacist-led education and follow-up service on anticoagulation control and safety outcomes at a tertiary hospital in China: a randomised controlled trial.

This study was designed to evaluate the impact of a pharmacist-led anticoagulation service on international normalised ratio (INR) control and other outcomes among patients receiving warfarin therapy at a tertiary hospital in Zhuhai, China. In this randomised controlled trial, adult patients who were newly initiated on warfarin with intended treatment duration of at least 3months were recruited. Participants were randomly allocated to receive the pharmacist-led education and follow-up service (PEFS) or usual care (UC). Anticoagulation control was calculated as the proportions of time within the target INR range (TTR) and time within the expanded target range (TER). A total of 152 participants (77 in the PEFS group and 75 in the UC group) were included. Within 180days after hospital discharge, the PEFS group spent more TER than the UC group (54.4% versus 42.0%; P=0.024), whereas the difference in TTR did not reach statistical significance (35.9% versus 29.5%; P=0.203). No major bleeding events were observed, and the cumulative incidences of major thromboembolic events (6.5% versus 9.3%) and mortality (1.3% versus 1.3%) were similar between the two groups (P>0.05). At 30days postdischarge, the PEFS group had better warfarin knowledge by answering 57.5% of questions correctly, compared with the UC group (43.0%) (P=0.003). The PEFS markedly enhanced anticoagulation control and warfarin knowledge but there was room for improvement. The expansion of pharmacists' clinical role and the development of more effective education and follow-up strategies are warranted to optimise anticoagulation management services in China.

Development of Multidisciplinary Anticoagulation Management Guidelines for Patients Receiving Durable Mechanical Circulatory Support.

Patients receiving durable mechanical circulatory support (MCS) require life-long anticoagulation with a vitamin K antagonist (VKA). Due to alternations in hemostasis, concomitant therapy with antiplatelet agents and critical illness, they are at increased risk of thromboembolic and bleeding complications compared with the general population managed on VKAs. To prevent thrombotic events, current guidelines recommend that patients with MCS receive long-term anticoagulation with a VKA to maintain a target international normalized ratio (INR) as specified by device manufacturers, but limited data exist regarding specific routine management of anticoagulation therapy and its potential complications. To optimize anticoagulation management and minimize risk in these patients, we have centralized anticoagulation management in a collaborative approach between the inpatient hemostatic and antithrombotic (HAT) stewardship service and between ambulatory anticoagulation management service (AMS) and the advanced heart disease team. Patients are followed by these three services beginning when the device is implanted and extending the duration that patients have the device. The teams include multiple clinicians from cardiac surgery, cardiology, hematology, pharmacy, nursing, case management, nutrition, and psychiatry, therefore, in order to standardize practice among clinicians without compromising patient centered decision making, we assembled an interdisciplinary team to create multiple treatment guidelines. In addition to a centralized and collaborative approach, our guidelines ensure seamless transitions of care between the inpatient and outpatient settings. We believe our approach has demontrated a positive improvement in the care of these challenging patients. In this article, we present our comprehensive centralized anticoagulation management approach for patients with left ventricular assist systems (LVAS).

Anticoagulation management by physician-clinical pharmacist team for patients with valvular atrial fibrillation

Objective To evaluate the effectiveness of anticoagulation management by physician-clinical pharmacist team for patients with valvular atrial fibrillation. Methods One hundred and seventy two patients with valvular atrial fibrillation received warfarin therapy for anticoagulation during hospitalization in Linyi People′s Hospital from January 2014 to December 2016, the patients continued to receive warfarin therapy for>6 months after discharge. The patients were randomly assigned in two groups: the anticoagulation management was given by physician-clinical pharmacist team in 87 cases (trial group), while the dosage of wargarin was adjusted in outpatient department by physicians alone in 85 cases (control group). The goal attainment rate of international normalized ratio (INR), the proportion of patients with a stable warfarin dose, knowledge of anticoagulants, belief of medication, medication compliance were compared between two groups. Results There were no significant differences in age, sex, body weight, smoking and drinking habits, valvular disease type, comorbidities; and the initial INR, knowledge of anticoagulants, belief of medication and medication compliance at admission between two groups (all P>0.05). The goal attainment rate of INR (52.17% vs. 41.02%, χ2=8.178,P=0.004), the proportion of patients with a stable dose of warfarin (74.71% vs. 56.47%, χ2=6.349, P=0.012), the knowledge of anticoagulants(11.03±2.25 vs. 10.08±1.86, t=3.018, P=0.003), the belief of medication[(12.23±2.07) vs.(11.67±1.48), t=2.042, P=0.043], and the medication compliance[(7.36±0.89) vs. (7.04±1.10), t=2.112 8, P=0.036] in the trial group were significantly higher than those in control group. Conclusion Anticoagulation management by physician-clinical pharmacist team can improve the management level of anticoagulation and the knowledge of anticoagulans, enhance the medication belief, improve the goal attainment rate of INR and the compliance rate of medication in patients with valvular atrial fibrillation. Key words: Atrial fibrillation; Warfarin; Anticoagulation management service; Physician; Clinical pharmacist; International normalized ratio

Role of the anticoagulant monitoring service in 2018: beyond warfarin.

The direct oral anticoagulants (DOACs) have a wide therapeutic index, few drug interaction, no dietary interactions and do not require dose adjustment according to the results of routine coagulation testing. Despite these advantages over warfarin, the DOACs remain high risk medications. There is evidence that non-adherence, off-label dosing and inadequate care transitions during DOAC therapy increase the risk of bleeding and thromboembolic complications. Although DOACs are approved for a growing number of indications, there remain patient populations who are not good candidates. Existing expertise within an Anticoagulation Management Service (AMS) should be leveraged to optimize all anticoagulant therapies including the DOACs. The AMS can facilitate initial drug therapy selection and dose management, reinforce patient education and adherence as well as managing drug interactions and invasive procedures. In the event that a transition to warfarin is warranted, the AMS is already engaged which limits the risk of fragmented patient care and ensures that therapeutic anticoagulation is re-established in a timely manner. The AMS of the future will provide comprehensive management for all patients receiving anticoagulant medications and continue to provide anticoagulation expertise to the healthcare team.

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. .

The future of anticoagulation management services: Ensuring and expanding patient access to pharmacists' care

The future of anticoagulation management services: Ensuring and expanding patient access to pharmacists' care

Integration of contraceptive services into anticoagulation management services improves access to long-acting reversible contraception

ObjectiveIntegration of services is a promising way to improve access to contraception in sub-Saharan Africa, but few studies have evaluated this strategy to increase access to contraception among women requiring anticoagulation. Our objective was to evaluate a model of care integrating contraceptive counseling and provision within an anticoagulation management clinic in Eldoret, Kenya, to determine the impact on long-acting reversible contraception (LARC) use. Study designWe performed a prospective observational study of reproductive-age women referred for integrated services from the anticoagulation management clinic at Moi Teaching and Referral Hospital from March 2015 to March 2016. All participants received disease-specific contraceptive counseling and provision, free reversible methods (excluding hormonal intrauterine devices [IUDs]) and follow-up care. We compared LARC use 3 months postintervention to preintervention using the proportions test. Logistic regression analysis was used to determine factors related to use of contraceptive implants and copper IUDs. ResultsOf 190 participants, 171 (90%) completed 3-month follow-up. There was a significant increase in contraceptive implant use from 10% to 19%, p=.02, and injectable contraceptive use from 14% to 24%, p=.013. There was a concomitant decrease in the use of no method/abstinence from 57% to 39% (33% decrease, p<.001). Younger age, having at least one child and discussing family planning with a partner were predictive of LARC use. ConclusionIntegrating contraceptive services into an anticoagulation management clinic increases the use of highly effective contraception for women with cardiovascular disease. Implementation of similar models of care should be evaluated within other sites for chronic disease management. ImplicationsA model of care integrating contraceptive counseling and provision into anticoagulation management services is an effective strategy to improve LARC and overall highly effective contraceptive use among women with cardiovascular disease requiring anticoagulation. This model of care may be utilized to prevent maternal morbidity and mortality among this high-risk population.

Anticoagulation management services in community pharmacy: Feasibility of implementing a quality improvement programme through a practice-based research network.

The literature has reported suboptimal real-world use of oral anticoagulants in patients with atrial fibrillation (AF). Anticoagulation management services (AMSs) in community pharmacy have rarely been evaluated, and no formal process is available to enable pharmacists to evaluate and improve their clinical practices. Our objective was to assess the feasibility of implementing, through a practice-based research network (PBRN), a quality improvement programme on AMSs by community pharmacists for AF patients and explore its impact on the quality of clinical practices and pharmacists' knowledge. An uncontrolled pre/post-pilot study was conducted through a PBRN. Pharmacists identified 5-20AF patients on oral anticoagulants per pharmacy and completed questionnaires at baseline (T0) and after 6months (T6). Clinical practices were evaluated using a set of quality indicators (QIs). QI scores ranged from 0% (no QI achieved) to 100% (all QIs achieved). The programme included an audit and feedback based on QIs and a personalized training programme (including online videos). Participation rates and satisfaction were documented. Mean changes (T6-T0), with 95% confidence interval (CI), in QIs and knowledge scores were computed. A total of 37 pharmacies (50 pharmacists) identified 222 patients who had received either vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), or both. All pharmacies received their baseline quality report (audit), and facilitators contacted by phone 97% of pharmacies (feedback). Each of the six online videos was completed by at least 48% of pharmacists. Baseline mean global QI scores for VKAs and DOACs were 39.1% (95% CI: 35.7%-42.4%) and 12.3% (7.8%-16.8%), respectively. Over a 6-month period, they increased by 12.5% points (7.5%-17.5%) and 9.9% points (3.8%-16.1%), respectively. Baseline mean global knowledge score was 68.7% (65.4%-72.0%) and increased by 4.3% points (1.2%-7.4%). Implementing a quality improvement programme for AMS in community pharmacy is relevant and feasible and may improve pharmacists' practices and knowledge.

Outcomes of warfarin therapy managed by pharmacists via hospital anticoagulation clinic versus online anticoagulation clinic

Background In response to the recognized difficulty in the management of patients on anticoagulation therapy, anticoagulation management services were developed in both hospital anticoagulation clinics (HACs) and an online anticoagulation clinic (OAC) by a pharmacist. Objective To compare monitoring outcomes and complications of warfarin therapy managed by pharmacists via hospitaloron-line. Setting The anticoagulation clinic of Fujian Medical University Union Hospital, China. Method A retrospective, observational cohort study was used to compare patients managed via hospital to those managed o-line between December 2015 and 2016. The primary outcome was the percentage of time in the therapeutic range (TTR). The secondary outcomes were the incidence rates of hemorrhagic events, thrombotic events and extreme international normalized ratio (INR) values. Results A total of 152 patients were evaluated; 70 patients managed in a HAC were compared to 82 patients managed via an OAC. There were no significant differences in the TTR (78.9 vs. 74.0%, P = 0.393) and adverse events [major bleeding events (0 vs. 1.2%, P = 1.000), minor bleeding events (10.0 vs. 9.8%, P = 0.960), thromboembolic events (0 vs. 0%, P = 1.000), warfarin-related emergency visits (2.9 vs. 3.7%, P = 1.000)], warfarin-related hospital admissions (0 vs. 1.2%, P = 1.000), and the incidence of subtherapeutic (3.0 vs. 3.8%, P = 0.148), and extreme total (8.4 vs. 5.8%, P = 0.135), between the groups managed via HAC and OAC. Patients managed in the HAC were more stable on warfarin, with a higher percentage of INR values within the target therapeutic range (80.2 vs. 71.9%, P = 0.005) and a lower incidence of supratherapeutic INR values (8.4 vs. 18.5%, P = 0.001) compared to patients managed via OAC. Conclusion The management of oral anticoagulation therapyon-line yielded similar clinical outcomes compared to that achieved by managementvia the hospital, although the incidence of supra-therapeutic INR values was increased.

Hospital admission rates of patients enrolled in pharmacist vs nurse anticoagulation management services

IntroductionVarious health care professionals provide dedicated anticoagulation management services (AMS). There is limited literature describing head‐to‐head trials comparing outcomes among different types of AMS.ObjectivesThe primary objective is to compare all‐cause hospitalizations between pharmacist‐ and nurse‐managed AMS. The secondary objectives are to characterize admissions, readmissions, and emergency department visits.MethodsThis study is a retrospective, observational cohort. Patients were included if they were 18 y of age or older and had an anticoagulation management consult for either the pharmacist‐ or nurse‐managed anticoagulation clinics from July 1, 2013 to June 30, 2014. Patients were excluded if they had a lapse of 10 wk without a point‐of‐care International normalized ratio draw or had a duration of warfarin management less than 2 wk. The study period included the duration of warfarin management or up to 1 y of warfarin management after the initial consult, whichever was shorter.ResultsA total of 824 and 547 patients were identified in the pharmacist‐ and nurse‐managed groups, respectively. A total of 250 patients were randomized in each arm. After accounting for exclusion criteria, 242 and 245 patients were included in the pharmacist‐ and nurse‐managed groups, respectively. Baseline characteristics differed between the groups based on poverty status, race, stroke risk score, previous admissions, and international status. The primary outcome occurred in 55 (22.7%) of the pharmacist‐managed patients and 86 (35%) of the nurse‐managed patients (P = 0.002). When accounting for differences in baseline characteristics, there was a statistically significant decrease in all‐cause hospitalizations in the pharmacist group (odds ratio = 0.63; 95% confidence interval [0.39‐0.98]). Indication for warfarin, types of admissions, emergency department visits, and 30‐d readmissions was similar between the groups. Time in therapeutic range was different between the groups.ConclusionThis hypothesis‐generating study found a difference in AMS performed by pharmacists and nurses. Pharmacists reduced hospitalization rates within the first year of AMS.

Majority of Total Joint Arthroplasties Are Subtherapeutic on Warfarin at Time of Discharge: Another Reason to Avoid Warfarin as a Venous Thromboembolism Prophylaxis?

BackgroundWarfarin has been used as prophylaxis against venous thromboembolism (VTE) after total joint arthroplasty (TJA) for over 60 years. With trends of shorter hospital stays for TJA patients, it is important to examine how many patients achieve therapeutic international normalized ratio (INR) at time of discharge. We aimed at elucidating the proportion of patients discharged at therapeutic INR and whether this is affected by inpatient specialty anticoagulation management service (AMS) involvement. MethodsWe conducted a retrospective review of 2927 primary TJA patients who received warfarin as postoperative VTE chemoprophylaxis from 2011 to 2016. An electronic chart query determined AMS input, length of stay (LOS), INR at discharge, and in-hospital complications. INR results were categorized as subtherapeutic (INR < 2.0), therapeutic (2.0 ≤ INR < 3.0), and supratherapeutic (INR ≥ 3.0). Descriptive statistics, chi-square, and t-tests were performed for analysis. ResultsAt discharge, 93.9% of patients had subtherapeutic INR. Average INR was 1.41 with average LOS of 2.53 days. Factors associated with being subtherapeutic included male gender, shorter LOS, fewer comorbidities, reduced in-hospital complications, and higher body mass index. AMS supervised postoperative warfarin dosing in 64.9% of patients. Patients managed by AMS were less likely to be subtherapeutic at discharge compared to those without AMS input; however, the absolute difference in INR may not be clinically significant. There were 19 VTEs, of which 13 had prolonged hospitalization to achieve therapeutic INR. ConclusionThe majority of patients are discharged at subtherapeutic INR levels despite management by AMS. Patients may not be adequately anticoagulated with warfarin at time of discharge, raising significant patient safety concerns as well as medicolegal implications.

Moving anticoagulation initiation and monitoring services into the community: evaluation of the Brighton and hove community pharmacy service

BackgroundAs part of the NHS desire to move services closer to where people live, and provide greater accessibility and convenience to patients, Brighton and Hove Clinical Commissioning Group (CCG) underwent a review of their anticoagulation services during 2008. The outcome was to shift the initiation and monitoring service in secondary care for non-complex patients, including domiciliary patients, into the community. This was achieved via a procurement process in 2008 resulting in the Community Pharmacy Anticoagulation Management Service (CPAMs) managed by Boots UK (a large chain of community pharmacies across the United Kingdom).MethodsThis evaluation aims to review the outcomes (International Normalised Ratio [INR] readings) and experiences of those patients attending the anticoagulation monitoring service provided by community pharmacists in Brighton and Hove. All patients on warfarin are given a target INR range they need to achieve; dosing of and frequency of appointment are dependent on the INR result. Outcome measures for patients on the CPAM service included percentage INR readings that were within target range and the percentage time the patient was within therapeutic range. Data collected from 2009 to 2016 were analysed and results compared to the service targets. Patient experience of the service was evaluated via a locally developed questionnaire that was issued to patients annually in the pharmacy.ResultsThe evaluation shows that community pharmacy managed anticoagulation services can achieve outcomes at a level consistently exceeding national and local targets for both percentage INR readings in therapeutic target range (65.4%) compared to the recommended minimum therapeutic target range of 60.0% and percentage time in therapeutic range (72.5%, CI 71.9–73.1%) compared to the national target of 70.0%. Patients also indicated they were satisfied with the service, with over 98.6% patients rating the service as good, very good or excellent.ConclusionThe Brighton and Hove CPAM service achieved above average national target management of INR and positive patient feedback, demonstrating that community pharmacy is ideally placed to provide this service safely and deliver enhanced clinical outcomes and positive patient experience.

Effect of increased time in the therapeutic range on atrial fibrillation outcomes within a centralized anticoagulation service

BackgroundClinical pharmacy anticoagulation services have improved the quality of anticoagulant therapy and are associated with lower rates of bleeding and thromboembolism compared to usual care. Several studies have found that higher time-in-therapeutic range (TTR) during warfarin therapy is associated with better warfarin outcomes. However, whether increasing TTR over time within an established anticoagulation service is associated with further reduction in bleeding and thromboembolic outcomes is unknown. MethodsThis was a retrospective cohort study of patients with atrial fibrillation conducted at an integrated healthcare delivery system with a centralized, pharmacist-managed anticoagulation service. Clinical outcomes (clinically-relevant bleeding, ischemic stroke or systemic embolism, and all-cause mortality) and TTR were compared between two distinct time periods: 1/1/2006 through 12/31/2007 (control group) and 1/1/2012 through 12/31/2013 (observation group) with regression modeling to adjustment for potential confounders. ResultsThere were 3641 and 4764 patients in the control and observation groups, respectively. The mean age was 74.3 years and 54.4% of the cohort was female. Mean TTR was higher in the observation group (70.5% vs. 63.4%, p < 0.001). The composite outcome of clinically-relevant bleeding, thromboembolism and all-cause mortality occurred in 4.6% and 3.6% of the control and observation groups, respectively (adjusted odds ratio = 0.69; 95% confidence interval 0.54–0.87). Individual rates of stroke/systemic embolism and all-cause mortality were each lower in the observation group (both p < 0.05) while clinically-relevant bleeding was not significantly different (p = 0.256). ConclusionIncreased TTR within a clinical pharmacy anticoagulation management service was associated with a lower risk of the composite outcomes of bleeding, thromboembolism and death in a large atrial fibrillation population receiving warfarin.

Comparison of Time in Therapeutic Range (TTR) in Patients Enrolled in the Anticoagulation Management Services Following Pharmacist Intervention

Comparison of Time in Therapeutic Range (TTR) in Patients Enrolled in the Anticoagulation Management Services Following Pharmacist Intervention

Expanding anticoagulation management services to include direct oral anticoagulants.

Despite the ease of use of direct oral anticoagulants (DOACs), these agents remain high risk medications and their clinical efficacy can be impacted by factors such as patient adherence, drug procurement barriers, bleeding leading to discontinuation, and prescribing that deviates from approved dosing regimens. Clinical monitoring of patients on DOACs should be performed by clinicians who specialize in anticoagulation and are familiar with the nuances of DOAC dosing, monitoring, and other components of anticoagulation management including peri-procedural management and care transitions. Although data for centralized warfarin management have consistently demonstrated improved clinical outcomes compared to traditional management by individual community providers, there are no published data addressing the impact of centralized management of DOACs on clinical outcomes or anticoagulation control. In addition, there is currently no consensus on how to incorporate patients on DOACs into this centralized model, despite recommendations for systematic follow-up by both the Anticoagulation Forum and the Institute for Safe Medication Practices. Based on the national recommendations and an identified institutional need, the Brigham and Women's Hospital Anticoagulation Management Service implemented a pilot program to expand services to include patients newly initiated on, or transitioned to, a DOAC. We describe our model for expansion of the AMS to include patients on DOACs.

Evaluation of a Standardized Perioperative Management Protocol in the Adult Hematology Anticoagulation Management Service.

In North America, 250,000 patients on vitamin K antagonists require surgical procedures each year. Temporary interruption of oral anticoagulation and perioperative bridging therapy with unfractionated heparin or low-molecular-weight heparin are recommended by the American College of Chest Physicians 2012 for select patients. The study objectives are to evaluate adherence and nonadherence to the Johns Hopkins clinic guidelines for perioperative management of anticoagulation and identify bleeding or thromboembolic events during perioperative management of anticoagulation. This is a retrospective study of patients who required perioperative management of anticoagulation for an invasive procedure from May 2009 to March 2014. Individualized perioperative anticoagulation management plans were prospectively developed for each patient according to the standardized Johns Hopkins perioperative bridging recommendations and documented in the medical record. Adherence to these standardized Johns Hopkins clinic guidelines, the incidence of thromboembolic events, and bleeding and adverse events during perioperative management were retrieved from the medical record. In 294 perioperative management cases, there was 1 (0.3%) thromboembolism, 3 (1%) major bleeds, and 21 (7%) minor bleeds. One patient experienced facial swelling after starting enoxaparin. There was no difference in thromboembolic (0 vs 1, P = 1.00), major (1 vs 2, P = 1.00), or minor bleeding (14 vs 7, P = 1.00) events in patients managed by providers who were adherent to guidelines when compared with providers who were nonadherent. Our study shows that using a standardized guideline for perioperative management of anticoagulation to inform but not to dictate clinical practice leads to low rates of both thromboembolism and bleeding.

Root Cause Analysis of Adverse Events in an Outpatient Anticoagulation Management Consortium

A number of factors can lead to adverse events (AEs) in patients taking warfarin. Performing a root cause analysis (RCA) of serious AEs is one systematic way of determining the causes of these events. Multidisciplinary teams were formed at Michigan Anticoagulation Quality Improvement Initiative (MAQI2) sites with organized anticoagulation management services (AMS). Medical records from patients who suffered serious AEs (major bleed, embolic stroke, venous thromboembolism) were reviewed, and AMS staff were interviewed to determine the root cause using the "5 Whys" technique. More than 600 patients had an AE and underwent screening by trained RNs. Of these, 79 required full review by a multidisciplinary panel. All potential contributing factors (comorbidities, concurrent medications, current protocols) were assessed to determine the main factor that caused the AE. Full RCA was completed in 79 cases. The main contributing factor was identified in 69/79 (87%) cases. Most identified AEs, 55/69 (80%), were due to patient-specific factors such as comorbidities. Patient-to-provider and provider-to-provider communication accounted for 16/69 (23%) of events and was the second most common cause. Other causes included protocol non-adherence and technology/equipment issues. After each detailed review, the multidisciplinary panel recommended system changes that addressed the primary cause. The majority of severe AEs for patients taking warfarin were related to nonmodifiable patient-related issues. The remaining AEs were primarily due to patient-to-provider and provider-to-provider communication issues. Methods for improving communication need to be addressed, and methods for more effective patient education should be investigated.

Comparing the effectiveness of pharmacist‐managed warfarin anticoagulation with other models: a systematic review and meta‐analysis

Anticoagulation management services are well known to improve the quality of patient care and to reduce the rates of hospitalization and emergency department visits following adverse events related to anticoagulation therapy. The complexity of managing warfarin has led to the development of a variety of specialized models managed by pharmacists, physicians, nurses, and self-managed care. The aim of the study is to compare the effectiveness of pharmacist-managed anticoagulation control of warfarin with other models. We performed a systematic literature search of the PubMed, Medline@Web of Knowledge, EMBASE, Cochrane Library and Cumulative Index to Nursing and Allied Health Literature to identify randomized controlled trials (RCTs) from database inception up to July 2015. The search terms used for the study were 'warfarin', 'pharmacists', 'Vitamin K antagonist', 'anticoagulation' and 'management model.' We used the Cochrane Collaboration's tool from the Cochrane Handbook to assess the risk of bias of RCTs. We performed statistical analyses using RevMan 5.3 and used the Grading of Recommendations, Assessment, Development, and Evaluations profiler to rate the quality of evidence of the outcomes. The anticoagulation control outcomes were the percentage of time within the standard and expanded therapeutic range and thrombosis events; the safety outcomes were bleeding events and mortality, and patients' satisfaction of anticoagulation service. Eight RCTs from 981 potentially relevant publications with a total of 1493 patients were included. Meta-analysis of the RCTs showed that a significant difference existed between pharmacist-managed care and other models for satisfaction (mean difference (MD)=0·41, 95% CI, 0·01-0·81, P=0·04, low-quality evidence) with heterogeneity, and the percentage of time within the standard therapeutic range (MD=3·66, 95% CI 2·20-5·11, P<0·00001, high-quality evidence) without heterogeneity. However, the pharmacist-managed group demonstrated no significant improvement on the percentage of time within the expanded therapeutic range (MD=2·85, 95% CI -0·56 to 6·26, P=0·10, moderate-quality evidence) with heterogeneity, mortality [odds ratio (OR)=0·97, 95% CI, 0·44-2·11, P=0·09, high-quality evidence] without heterogeneity, the prevention of bleeding events (OR=0·89, 95% CI, 0·56-1·44, P=0·64, high-quality evidence) without heterogeneity, and thrombosis events (OR=0·81, 95% CI, 0·34-1·92, P=0·64, high-quality evidence) without heterogeneity. The advantage of pharmacist-managed warfarin anticoagulation therapy in terms of anticoagulation control, safety and mortality are unclear, but resulted in significantly better patient satisfaction. Compared with other models, the superiority of pharmacist-managed warfarin anticoagulation needs to be further evaluated and validated in future research.

Modelling the cost-effectiveness of pharmacist-managed anticoagulation service for older adults with atrial fibrillation in Singapore

Background Oral anticoagulation with warfarin is the cornerstone therapy in atrial fibrillation (AF) for stroke prevention. Multi-disciplinary anticoagulation management services have been shown to be cost-effective in the United States, Hong Kong and Thailand, but the findings are not readily generalizable to Singapore's healthcare system. Objective This study aimed to evaluate the cost-effectiveness of pharmacist-managed anticoagulation clinic (ACC) compared with usual care (UC) for the management of older adults with AF receiving oral anticoagulation with warfarin. Setting Pharmacist-managed ACC in an academic medical centre. Method A Markov model with 3-month cycle length and 30-year time horizon compared costs and quality-adjusted life-years (QALYs) of ACC and UC from the patient's and healthcare provider's perspectives. Four pathways based on time in therapeutic range (TTR) were: ACC TTR<70%, ACC TTR≥70%, UC TTR<70% and UC TTR≥70%. A hypothetical cohort of 70-year-old Singaporean AF patients receiving warfarin was utilised. Local data from national disease registries, patient surveys and hospital databases were used. When local data was not available, published studies on Asian populations were utilized when available. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to account for uncertainties. Costs and QALYs were discounted annually by 3%. Main outcome measure Costs and QALYs of ACC and UC. Results Pharmacist-managed ACC was found to dominate UC in all comparisons. It improved effectiveness by 0.19 and 0.13 QALYs at TTR<70% and TTR≥70% respectively compared with UC. From the patient's perspective, ACC reduced costs by SG$1222.67 (€1110.24) for TTR<70% and SG$1008.16 (€915.46) for TTR≥70%. Similar trends were observed from the healthcare provider's perspective, with ACC reducing costs by SG$1444.79 (€1311.94) for TTR<70% and SG$1269.17 (€1152.46) for TTR≥70% compared with UC. The results were robust to variations of the parameters over their plausible ranges in one-way sensitivity analyses. Probabilistic sensitivity analyses demonstrated that ACC was cost-effective more than 79% of the time from both perspectives at a willingness-to-pay threshold of SG$69,050 (€62,701) per QALY. Conclusion Pharmacist-managed ACC is more effective and less costly compared with UC regardless of the quality of anticoagulation therapy. The findings support the current body of evidence demonstrating the cost-effectiveness of ACC.

Fluctuations in warfarin dose response after heart valve surgery: implications for cardiac rehabilitation

In patients undergoing heart valve surgery (HVS) who require warfarin therapy, the maintenance of low variability in the level of anticoagulation early after operation is generally difficult. Aim of this study was to evaluate the time in therapeutic range (TTR) in HVS patients receiving oral anticoagulation therapy (OAT) during phase I-II of cardiac rehabilitation (CR), and, secondly, to identify clinical variables associated with inadequate anticoagulation. Observational study of consecutive in-hospital patients directly tracked from a cardiac surgery unit to a CR facility. OAT was monitored both in terms of administered warfarin doses and resulted INR values, from day 1 to day 15 after operation. Clinical variables were tested in a logistic regression model for the prediction of inadequate anticoagulation, defined as the presence of nontherapeutic INRs for > or = 5 days between day 8 and 15. Eighty-one patients (males 56%, age 62 +/- 19 yrs.), following valvuloplasty (37%), mechanical (17%), and bioprosthetic (45%) valve replacement were considered. The prescribed warfarin dosages were significantly higher from day 1 to day 7 than from day 8 to day 15 (4.6 +/- 3.6 and 3.0 +/- 1.1 mg respectively, p< 0.001). Overall, TTR was 6 +/- 3 days, while time with elevated and lower INRs accounted for 1.3 +/- 1.6 and 8.0 +/- 3.5 days respectively. At day 7, only 25% of patients (n= 20) showed a therapeutic INR value. Inadequate anticoagulation between postoperative day 8 and 15 was displayed in 41 (51%) patients, with hypertension as the only independent predictor (p< 0.001) at multivariate analysis. Despite intensive monitoring, half of patients have nontherapeutic INR values (mainly subtherapeutic) in the first two weeks after HVS while on warfarin. Giving the high risk of completing the hospitalization phase without a stable OAT in many patients, both cardiac surgeons and cardiologists should not miss the opportunity to improve patients education, and consider a direct track to anticoagulation management services after discharge.