Warfarin Management Research Articles

Warfarin Management

Until recently, most patients taking warfarin (brand name Coumadin) had to visit a laboratory and/or clinic every few weeks for an international normalized ratio (INR) blood test and adjustment of their warfarin dose. It is now possible for a patient to measure his/her INR (self-testing) with a finger-stick drop of blood with use of a small, portable, battery-powered device. Some self-testing patients adjust their dose of warfarin (self-dosing) based on a set of instructions. Even more recently, online systems have been developed to facilitate and improve self-testing and self-dosing. Patients who use self-testing have described it as life changing. A video on the ease and benefits of self-testing by a physician-patient named Dr Michael Schwartz can be viewed on ClotCare at www.clotcare.org/inrselftestingvideo.aspx. Yes. The additional benefits are why Medicare and other insurance companies started paying for self-testing for most patients in March 2008. To understand the other potential benefits, however, one needs some background information. Warfarin is used to prevent blood clots that cause strokes, heart attacks, or other life-threatening conditions. If the dose of warfarin is too small, the INR will be low, and a patient may get a blood clot. If the dose is too large, the INR will be high, and a patient …

Practice Guidelines for Reversal of New and Old Anticoagulants

ommonly called “conventional anticoagulants,” heparins and warfarin re the most commonly used treatment of acute clot formation and thromosis prophylaxis. Usually associated with cardiopulmonary bypass, the eed for heparin reversal has been identified in recent years as being more ikely to occur in general practice as therapeutic and prophylactic ndications for anticoagulation are applied to a greater proportion of the opulation. By contrast, warfarin is known to carry an increased risk of ajor hemorrhage of 1%-3% per year, which increases with age and omorbidities. Professional organizations, such as the American ollege of Chest Physicians (ACCP), have published recommendations n management of warfarin with respect to reversal in emergent and onemergent scenarios (Table 1). Intracranial hemorrhage, although ot the most common warfarin-associated bleed (ie, gastrointestinal emorrhage), is more frequently fatal. Hemorrhagic complications of arfarin anticoagulation have prompted clinicians to look for the most ffective reversal strategies in patients at risk of life-threatening hemorhage. The comfort of conventional anticoagulants is that they have been tudied more extensively and have readily available reversal agents in the vent of overdose, hemorrhage, or surgical preparation. In part, however, t was the weaknesses of unfractionated heparin and warfarin—less redictable anticoagulant profile, more frequent dosing and laboratory onitoring, and relatively poor safety profile—that encouraged the evelopment of newer anticoagulant agents. The newest additions include he indirect and direct factor Xa inhibitors, and direct thrombin inhibitors, hich are gaining usage in the USA. It is this globally increased usage of both old and new anticoagulants— or a host of conditions, including atrial fibrillation, deep venous hrombosis/pulmonary embolism, acute coronary syndrome, immobi-

Cost-effectiveness of dabigatran versus genotype-guided management of warfarin therapy for stroke prevention in patients with atrial fibrillation.

BackgroundDabigatran is associated with lower rate of stroke comparing to warfarin when anticoagulation control is sub-optimal. Genotype-guided warfarin dosing and management may improve patient-time in target range (TTR) and therefore affect the cost-effectiveness of dabigatran compared with warfain. We examined the cost-effectiveness of dabigatran versus warfarin therapy with genotype-guided management in patients with atrial fibrillation (AF).Methodology/Principal FindingsA Markov model was designed to compare life-long economic and treatment outcomes of dabigatran (110 mg and 150 mg twice daily), warfarin usual anticoagulation care (usual AC) with mean TTR 64%, and genotype-guided anticoagulation care (genotype-guided AC) in a hypothetical cohort of AF patients aged 65 years old with CHADS2 score 2. Model inputs were derived from literature. The genotype-guided AC was assumed to achieve TTR = 78.9%, adopting the reported TTR achieved by warfarin service with good anticoagulation control in literature. Outcome measure was incremental cost per quality-adjusted life-year (QALY) gained (ICER) from perspective of healthcare payers. In base-case analysis, dabigatran 150 mg gained higher QALYs than genotype-guided AC (10.065QALYs versus 9.554QALYs) at higher cost (USD92,684 versus USD85,627) with ICER = USD13,810. Dabigatran 110 mg and usual AC gained less QALYs but cost more than dabigatran 150 mg and genotype-guided AC, respectively. ICER of dabigatran 150 mg versus genotype-guided AC would be >USD50,000 (and genotype-guided AC would be most cost-effective) when TTR in genotype-guided AC was >77% and utility value of warfarin was the same or higher than that of dabigatran.Conclusions/SignificanceThe likelihood of genotype-guided anticoagulation service to be accepted as cost-effective would increase if the quality of life on warfarin and dabigatran therapy are compatible and genotype-guided service achieves high TTR (>77%).

The benefits of pharmacist-delivered warfarin education in the home

Good warfarin knowledge is important for optimal patient outcomes, but barriers exist to effective education and warfarin knowledge is often poor. This study aimed to explore the educational outcomes of home-based warfarin education provided by trained pharmacists. In a prospective, non-randomised, controlled cohort trial, patients received either usual community-based post-discharge care or a post-discharge warfarin management service, including warfarin education by trained pharmacists during two or three home visits. Patients' warfarin knowledge was assessed at 8 and 90 days post-discharge using the Oral Anticoagulation Knowledge test. One hundred and thirty-nine patients were recruited into the usual care group between November 2008 and August 2009, and 129 into the intervention group between May and December 2009. Pharmacist-delivered warfarin education was associated with a significant difference between the intervention patients' baseline and day 8 mean warfarin knowledge scores of 64.5% (95% confidence interval (CI) 61.0-68.5%) and 78.0% (95% CI 74.5-81.5%; P < 0.001), respectively. The intervention patients also scored significantly higher than the usual care patients at day 8 (65.0%, 95% CI 61.5-68.0%; P < 0.001), but not at day 90. Use of an existing healthcare framework overcame several systemic barriers by facilitating warfarin education in patients' homes. While the intervention was associated with better short-term warfarin knowledge, follow-up may be required to optimise its benefits. Widespread implementation of home-based warfarin education by pharmacists has the potential to contribute significantly to improved outcomes from warfarin therapy.

A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: The Randomized, phase II study to Evaluate the sAfety and pharmacokinetics of oraL dabIGatran etexilate in patients after heart valve replacemeNt (RE-ALIGN)

Vitamin K antagonists are the only oral anticoagulants approved for long-term treatment of patients with a cardiac valve replacement. This study aims to test a new dosing regimen for dabigatran etexilate in patients with a mechanical bileaflet valve. Patients aged ≥ 18 years and ≤ 75 years, either undergoing implantation of a mechanical bileaflet valve (aortic or mitral or both) during the current hospital stay or having undergone implantation a mitral bileaflet valve >3 months before randomization, will be randomized between dabigatran etexilate or warfarin (in a ratio of 2:1) in an open-label design. Initial doses of dabigatran will be based on the estimated creatinine clearance, and the doses will be adjusted based on measuring trough dabigatran plasma levels to achieve levels ≥ 50 ng/mL at steady state. Doses will range between 150 mg twice a day and 300 mg twice a day. Warfarin management and target international normalized ratio will be according to current practice guidelines at the discretion of the treating physicians. The plan is to treat 270 patients with dabigatran etexilate for a total study population of approximately 405 patients. Clinical efficacy and safety outcomes will be analyzed in an exploratory manner. RE-ALIGN is the first study to test an alternative to warfarin in patients with mechanical heart valves. A definitive phase III study will be planned based on the results of this study.

PCV41 Analysis of Direct Costs Associated with INR Monitoring and Warfarin Dose Ajustment in Patients with Atrial Fibrillation

To analyze the structure of expenses associated with warfarin dose adjustment and consequent international normalized ratio (INR) monitoring for effective stroke prevention in patients with atrial fibrillation. The present study was designed as cost of illness analysis. Expenses associated with INR monitoring and warfarin dose adjustment were calculated for four different circumstances: 1) for obligatory medical insurance system according the current general tariff agreement; 2) for patients managed in outpatient department of University hospital using prices for consultations and coagulation tests; 3) for those controlling INR in commercial laboratory using their price list; and 4) for self-monitored patients using costs for coagulomether and test strips purchasing. Within the obligatory medical insurance system total expenses for warfarin management accounted for 4058 Roubles/person per year, but share of expenses for warfarin purchasing was less than 1 %; for patients treated in outpatient department of University clinic that estimated for 13019 Roubles/person per year and 0.03%; in the case of INR control in commercial laboratory – 18648 Roubles/person per year and 0.02%; and for self-moniroring – from 40,405 Roubles/person per year (0.01%) in the first year (that includes the fee for coagulomether purchasing) to 7405 Roubles/person per year (0.05%) in consequent years respectively. Regardless the strategy of INR control, concomitant expenses associated with warfarin dose adjustment and subsequent efficiency and safety monitoring is more than 100-fold higher than the price of warfarin itself.

Warfarin Anticoagulation After Congenital Heart Surgery at a Large Children’s Hospital

Management of warfarin in pediatric patients remains a clinical challenge. Warfarin may be administered after congenital heart surgery, and the risks of morbidity can be high. Currently, no data exist to describe the initiation of warfarin and the risk factors for morbidity in post-congenital heart surgery patients. This study aimed to characterize the time required to reach anticoagulation for patients administered warfarin therapy after cardiac surgery and to identify and characterize the risk factors for supratherapeutic anticoagulation and adverse events after warfarin initiation. This retrospective study reviewed all patients between 2006 and 2011 who received warfarin anticoagulation after cardiac surgery at our institution. Factors associated with a prolonged time required to reach an international normalized ratio (INR) of 2 and factors related to supratherapeutic anticoagulation (INR ≥ 4) were identified. The inclusion criteria were met by 59 patients. The median time required to reach an INR of at least 2 after initiation of warfarin was 2 days (interquartile range (IQR), 2-4). The only groups that required a significantly longer time to reach an INR of 2 were those with a postoperative delay in initiation of warfarin and those receiving heparin anticoagulation before and during warfarin initiation. Nine patients experienced an INR of 4 or more. However, no thrombotic events occurred, and significant bleeding was uncommon. In the largest reported group of patients undergoing anticoagulation after cardiac surgery, warfarin was well tolerated across all age groups. The median time required to reach an INR of 2 after loading with warfarin was 2 days, and adverse events were uncommon.

Use of warfarin in long-term care: a systematic review.

BackgroundThe use of warfarin in older patients requires special consideration because of concerns with comorbidities, interacting medications, and the risk of bleeding. Several studies have suggested that warfarin may be underused or inconsistently prescribed in long-term care (LTC); no published systematic review has evaluated warfarin use for stroke prevention in this setting. This review was conducted to summarize the body of published original research regarding the use of warfarin in the LTC population.MethodsA systematic literature search of the PubMed, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library was conducted from January 1985 to August 2010 to identify studies that reported warfarin use in LTC. Studies were grouped by (1) rates of warfarin use and prescribing patterns, (2) association of resident and institutional characteristics with warfarin prescribing, (3) prescriber attitudes and concerns about warfarin use, (4) warfarin management and monitoring, and (5) warfarin-related adverse events. Summaries of study findings and quality assessments of each study were developed.ResultsTwenty-two studies met the inclusion criteria for this review. Atrial fibrillation (AF) was the most common indication for warfarin use in LTC and use of warfarin for stroke survivors was common. Rates of warfarin use in AF were low in 5 studies, ranging from 17% to 57%. These usage rates were low even among residents with high stroke risk and low bleeding risk. Scored bleeding risk had no apparent association with warfarin use in AF. In physician surveys, factors associated with not prescribing warfarin included risk of falls, dementia, short life expectancy, and history of bleeding. International normalized ratio was in the target range approximately half of the time. The combined overall rate of warfarin-related adverse events and potential events was 25.5 per 100 resident months on warfarin therapy.ConclusionsAmong residents with AF, use of warfarin and maintenance of INR levels to prevent stroke appear to be suboptimal. Among prescribers, perceived challenges associated with warfarin therapy often outweigh its benefits. Further research is needed to explicitly consider the appropriate balancing of risks and benefits in this frail patient population.

Non-adherence to warfarin: a case study

Atrial fibrillation (AF) is a major risk factor for stroke, requiring monitoring and treatment. If there are no significant risk factors, warfarin therapy may be prescribed for some types of AF, but necessitates compliance, careful monitoring and dose adjustment. Many factors influence the effectiveness of warfarin therapy, including alcohol consumption, dietary constituents, herbal supplements, and prescribed or over-the-counter medicines. Compliance, in turn, can be affected by factors such as the presence of dementia or cognitive impairment. As exemplified in this case study, a structured approach for the management of warfarin should be adopted, ensuring factors affecting compliance or drug effectiveness may be identified and appropriate action can be taken.

Inpatient warfarin: Experience with a pharmacist-led anticoagulation management service in a tertiary care medical center

The implementation of a pharmacist-led anticoagulation management service (AMS) and the clinical outcomes of inpatients receiving warfarin management are described. An AMS was established at St. Mary's Medical Center (SMMC) in Duluth, Minnesota, in November 2003 at the request of orthopedic surgeons to manage warfarin for their patients postoperatively. The AMS was also available to other inpatients by physician request. All AMS pharmacists received didactic and experiential training. Each day, the managing pharmacist, usually the decentralized pharmacist, was responsible for checking the patients' International Normalized Ratio (INR); reviewing other pertinent laboratory test values, any medication changes, and vital signs; monitoring changes in the patients' clinical status, and writing an order for a warfarin dose. A database was created to help monitor patients managed by the AMS and to analyze monthly outcomes data. Clinical outcomes data were evaluated to identify areas of improvement for the AMS. All hospitalizations for patients who received anticoagulation therapy with warfarin managed by the AMS from January 1, 2006, through August 31, 2007, were analyzed. Primary endpoints, including thrombosis and bleeding complications during hospitalization, were identified for inclusion in the final hospital discharge data. Of the 2794 hospitalizations for patients managed by the AMS evaluated, 59 complications were identified. Of these, 14 (0.5%) were thrombosis events and 45 (1.6%) were bleeding events. INR results were also analyzed as secondary endpoints. The evaluation of outcomes of the inpatient-based AMS at SMMC provided critical information to the anticoagulation subcommittee for consideration of quality-improvement efforts.

Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation

We performed a randomised pilot trial of PerMIT, a novel decision support tool for genotype-based warfarin initiation and maintenance dosing, to assess its efficacy for improving warfarin management. We prospectively studied 26 subjects to compare PerMIT-guided management with routine anticoagulation service management. CYP2C9 and VKORC1 genotype results for 13 subjects randomly assigned to the PerMIT arm were recorded within 24 hours of enrolment. To aid in INR interpretation, PerMIT calculates estimated loading and maintenance doses based on a patient's genetic and clinical characteristics and displays calculated S-warfarin plasma concentrations based on planned or administered dosages. In comparison to control subjects, patients in the PerMIT study arm demonstrated a 3.6-day decrease in the time to reach a stabilised INR within the target therapeutic range (4.7 vs. 8.3 days, p = 0.015); a 12.8% increase in time spent within the therapeutic interval over the first 25 days of therapy (64.3% vs. 55.3%, p = 0.180); and a 32.9% decrease in the frequency of warfarin dose adjustments per INR measurement (38.3% vs. 57.1%, p = 0.007). Serial measurements of plasma S-warfarin concentrations were also obtained to prospectively evaluate the accuracy of the pharmacokinetic model during induction therapy. The PerMIT S-warfarin plasma concentration model estimated 62.8% of concentrations within 0.15 mg/l. These pilot data suggest that the PerMIT method and its incorporation of genotype/phenotype information may help practitioners increase the safety, efficacy, and efficiency of warfarin therapeutic management.

Conservative Peri-Procedural Anticoagulation Management in Patients with Venous Thromboembolic Disease Results in a Low Proportion of Thrombosis and Bleeding

Abstract 546The optimal strategy for peri-procedural warfarin management in patients with venous thromboembolic disease (VTE) is unknown because most studies to date have included small proportions of VTE patients. Guidelines are largely based on expert opinion and recommend low-molecular-weight heparin (LMWH) bridging in patients at high or moderate risk for VTE. LMWH bridging may be associated with an increased bleeding risk, which if occurs, would result in temporary cessation of anticoagulation (AC) potentially leading to a paradoxical increased thrombotic risk. We conducted a single-center retrospective cohort study to examine the effectiveness of conservative peri-procedural AC management in VTE (DVT or PE) patients.We included all patients from our institution’s thrombosis unit between 1993 and 2011 who required peri-procedural AC management for planned procedures. The thrombosis unit has, on average, 800 patients on chronic AC for VTE. Patients were excluded if they had other indications for AC, had an acute VTE <90 days before the procedure, or had no follow-up after the procedure. Our centre uses a conservative bridging strategy in these patients consisting of holding warfarin 5 days before the procedure without administering LMWH. Postoperatively all patients resume warfarin as soon as they can swallow. For ambulatory procedures no LMWH is given after the procedure, whereas patients undergoing in-hospital procedures are usually given prophylactic LMWH starting the morning after surgery until discharge or when the INR is therapeutic, whichever occurs first. The primary outcome was incidence of VTE within 90 days of the procedure. Secondary outcomes were 90-day incidence of major and total bleeding and all-cause mortality. Confidence intervals for proportions were calculated using the Wilson’s score method. Groups were compared using χ2 or Fisher’s exact tests. Survival analysis was done using the Kaplan-Meier method. Two-sided p values ≤0.05 were considered statistically significant.During the study period there were 634 procedures in 416 patients (47.4% males). The mean age was 64.9 years (SD 15.8) and 79.1% of patients had idiopathic VTE. There were 156 procedures (24.6%) completed in-hospital. Pre- and post-procedure bridging was used in 15 (2.4%) and 153 (24.1%) procedures, respectively. The 90-day cumulative incidence of VTE was 0.63% (95% CI 0.25–1.61). The VTE events were 4 DVTs (postoperative day 3, 29, 41, 43) with no associated mortality. The 90-day cumulative incidence of major and total bleeding events was 1.58% (95% CI 0.86–2.88) and 3.47% (95% CI 2.30–5.20), respectively. All-cause mortality rate was 0.63% (95% CI 0.25–1.61); one patient died from a myocardial infarction 3 days after an abdominal aortic aneurysm repair, a second died from an ischemic stroke the morning of a colonoscopy and 2 patients had non-VTE related deaths.The effects of type of procedure and use of bridging on outcomes are shown in Table 1. The use of pre- or post-procedure bridging was not associated with VTE or bleeding. There were significantly more total bleeding events with inpatient procedures. There was a significant correlation between bleeding and VTE events: 13.6% of patients with any bleeding and 30% with major bleeding developed a VTE complication compared with 0.2% of those without bleeding. Spearman’s correlation coefficients were 0.311 and 0.470, respectively (p<0.001). Two postoperative DVTs (50%) developed after warfarin was held for an extended period of time (1 major bleed, 1 neurosurgical complication).Conservative peri-procedural AC management in VTE patients on warfarin for at least 3 months results in a low risk of thrombotic and bleeding events. A randomized controlled trial in chronically anticoagulated VTE patients is needed to provide definitive conclusions but a conservative approach appears promising.Effect of Type of Procedure and Bridging on OutcomeOutcomeVTE N (%)No (N=630)Yes (N=4)PInpatient procedure154 (24.4%)2 (50%)0.255Pre-procedure bridging15 (2.4)0 (0)1Post-procedure bridging151 (24)2 (50)0.247Total Bleeding N (%)No (N=612)Yes (N=22)Inpatient procedure146 (23.9)10 (45.5)0.039Pre-procedure bridging15 (2.5)0 (0)1Post-procedure bridging147 (24)6 (27.3)0.800Major bleeding N (%)No (N=624)Yes (N=10)Inpatient procedure153 (24.5)3 (30)0.714Pre-procedure bridging15 (2.4)0 (0)1Post-procedure bridging151 (24.2)2 (20)1 Disclosures:Lazo-Langner:Pfizer Inc.: Honoraria; Leo Pharma: Honoraria.

Warfarin management in patients on continuous anticoagulation therapy undergoing total knee replacement

We evaluated the safety and efficacy of total knee replacement in patients receiving continuous warfarin therapy. We identified 24 consecutive patients receiving long-term warfarin therapy who underwent total knee replacement between 2006 and 2008 and compared them with a group of age- and gender-matched patients not on long-term anticoagulation. Primary observations were changes in haemoglobin, transfusion rates and complications. Secondary observations were fluctuations in the international normalised ratio (INR) and post-operative range of movement. There was no significant difference between the two groups in pre- or post-operative haemoglobin, incidence of transfusion or incidence of post-operative complications. There were no surgical delays due to a high INR level. The mean change in INR during the peri-operative phase was minimal (mean 0.4; SD 0.7). There was no significant difference in the range of movement between the two groups after day two post-operatively. Current American College of Chest Physicians guidelines recommend bridging therapy for high-risk patients receiving oral anticoagulation and undergoing major orthopaedic procedures. We have shown that a safe alternative is to continue the steady-state warfarin peri-operatively in patients on long-term anticoagulation requiring total knee replacement.

Abstract P205: Anticoagulation Volume Does Not Predict Facility Performance of Time in Therapeutic INR Range of Patients With Atrial Fibrillation: A National VA Study

Introduction: Effectiveness of warfarin for stroke prevention in atrial fibrillation (AF) is proportional to the time in INR therapeutic range of 2.0-3.0. Time in therapeutic range (TTR) ≥ 58% is a validated threshold at which warfarin has benefit over aspirin, while TTR &lt; 40% may cause net harm due to hemorrhage. Variation of TTR across facilities may be due to systematic or facility-based factors, including patient volume. We evaluated the relationship of anticoagulation facility patient volume and TTR. Methods: We performed a national cohort study of Veterans Health Administration data using centralized medical and administrative records. We identified 48,192 patients with at least two outpatient ICD-9 diagnoses of AF who were prescribed warfarin from 94 VA anticoagulation facilities in FY 2003-04. The primary outcome was facility TTR, which was mean TTR calculated for FY04 from all patient-level TTRs of that facility. Patient-level TTR was calculated using the modified Rosendaal method, using linear imputation of INR values up to a maximum of 56 days. Results: Excluding two outliers with TTR &lt; 1%, the mean TTR across 92 facilities was 54.6% ± 6.1% (95% CI 43.7%-63.0%). Only 30 of 92 facilities (33%) had a mean TTR ≥ 58%, and 2 (2.2%) had a mean TTR &lt; 40%. Facility volume, as measured by the number of identified patients per facility, was not related to TTR (R-squared 2.6%) although facility INR test frequency was related to TTR (R-squared 29%). After multivariate adjustment for facility volume and facility prevalence of diabetes, heart failure, hypertension, coronary disease, stroke/TIA, and mean patient age, INR test frequency was significantly associated with TTR ≥ 58% (p &lt; 0.001), while facility volume remained insignificant (p=0.55). For every three additional INR tests per month, the adjusted odds of achieving TTR ≥ 58% increased 5.33 (p &lt; 0.001). Conclusions: We found systematic variation of facility TTR in a national health care system. Facility volume did not predict quality of anticoagulation. However, the facility's mean INR frequency is strongly associated with its overall quality of anticoagulation of patients with AF. Standardization and improvement of warfarin management across facilities may improve quality and prevent adverse outcomes.

Warfarin management after discharge from hospital: a qualitative analysis

Warfarin is recognized as a high-risk medication for adverse events, and the risks are particularly heightened in the period immediately following a patient's discharge from hospital. This qualitative study aimed to explore the experiences of Australian patients and healthcare professionals of warfarin management in the post-discharge period and identify the benefits and deficiencies of existing systems, to inform the development of a model for a new collaborative post-discharge warfarin management service. Healthcare professionals, professional organization representatives and patients recently discharged from hospital taking warfarin (consumers) were recruited via purposive, criterion-based sampling within two Australian states. Semi-structured telephone interviews were conducted between August and October 2008 using standard discussion guides. Data were manually analyzed to identify emergent themes using a phenomenological approach. Forty-seven participants were involved in the telephone interviews. Three major themes emerged: (i) appropriate warfarin education is integral to effective warfarin management, (ii) problems occur in communication along the continuum of care and (iii) home-delivered services are valuable to both patients and healthcare professionals. Although high-quality warfarin education and effective communication at the hospital-community interface were identified as important in post-discharge warfarin management, deficiencies were perceived within current systems. The role of home-delivered services in ensuring timely follow-up and promoting continuity of care was recognized. Previous studies exploring anticoagulation management in other settings have identified similar themes. Post-discharge management should therefore focus on providing patients with a solid foundation to minimize future problems. Addressing the three identified facets of care within a new, collaborative post-discharge warfarin management service may address the perceived deficiencies in existing systems. Improvements may result in the short- and longer-term health outcomes of patients discharged from hospital taking warfarin, including a reduction in their risk of adverse events.

316 Patient satisfaction with anticoagulation clinics across Alberta

316 Patient satisfaction with anticoagulation clinics across Alberta

Effect of chronic kidney disease on warfarin management in a pharmacist-managed anticoagulation clinic.

There is growing evidence that kidney disease affects hepatically cleared drugs. Accordingly, we hypothesized that chronic kidney disease (CKD) would disrupt anticoagulation of warfarin-treated patients and thereby increase the amount of management required to maintain appropriate anticoagulation. Specifically, we anticipated that more dose manipulations (both dose changes and transient dose adjustments) and shorter times between scheduled clinic visits would be required for anticoagulation patients with CKD. To determine how CKD affected warfarin maintenance dose, anticoagulation stability, the proportion of clinic visits that necessitated a dose manipulation (either a change in the prescribed weekly dose or a transient dose adjustment), and the length of time between scheduled visits in 2 pharmacist-managed anticoagulation clinics. Our retrospective, cohort chart review investigated warfarin response in anticoagulation clinic patients. From the clinic database of patients with an international normalized ratio (INR) target range of 2.0-3.0, we matched 20 of 24 patients with CKD (estimated creatinine clearance less than 60 mL per minute) to 20 comparison group patients (estimated creatinine clearance greater than 60 mL per minute) based on parameters demonstrated to affect warfarin dose: ethnicity, gender, age, body surface area, and simvastatin use. We calculated the average weekly dose used to maintain target INR (assessment period range=116-1,408 days). To evaluate anticoagulation stability and patient management, we quantified several parameters, including the percentage of total time in therapeutic range, the proportion of clinic visits that required a dose change, and the time between scheduled visits. We compared group means using t-tests, and categorical data were compared using Fisher's exact test. Our population was predominantly female (75%) and of African ancestry (95%); average age 60 years. Patients with CKD required a 24% lower dose than the comparison group (mean [SD]=35.9 [10.7] vs. 47.0 [11.2] mg per week, P=0.003) and spent less time in therapeutic range required increased clinic management versus the comparison group, as indicated by a significantly higher proportion of clinic visits at which dose changes occurred (22% vs. 12%, P<0.001) and a decreased time between scheduled visits (mean [SD] of 16.0 [3.2] days vs. 19.7 [3.4] days, respectively, P=0.001). CKD was associated with both decreased warfarin maintenance dose and decreased anticoagulation stability which, in turn, required more frequent and intensive anticoagulation clinic management.

Hospital Budget Implications of Substituting Dabigatran for Warfarin in an Anticoagulation Service

The aim of our study was to assess hospital budget implications of substituting dabigatran for warfarin in patients enrolled in a large anticoagulation service. The study population was identified using criteria from randomized controlled trials of dabigatran. We obtained labor costs ($483 per patient) from the hospital's anticoagulation service budget, laboratory costs of international normalized ratio (INR) tests ($267 per patient), and wholesale costs of warfarin 5 mg tablets ($31 per patient) and dabigatran 150 mg capsules ($2464 per patient). A total of 1774 (93.5%) of 1898 patients were eligible to substitute dabigatran for warfarin. The annual projected hospital expense for anticoagulation with dabigatran was $4,371,136, attributable to drug cost alone. The annual projected cost of warfarin management was $1,385,494. This was comprised of $856,842 for labor, $473,658 for INR testing, and $54,994 for the drug cost of warfarin. Substitution will result in increased expense due to drug cost.

Major bleeding risk associated with warfarin and co‐medications in the elderly population

Warfarin management in the elderly population is complex as medicines prescribed for concomitant diseases may further increase the risk of major bleeding associated with warfarin use. We aimed to quantify the excess risk of bleeding-related hospitalisation when warfarin was co-dispensed with potentially interacting medicines. A retrospective cohort study was undertaken over a 4-year period from July 2002 to June 2006 to examine bleeding risk associated with medications co-administered in patients taking warfarin using an administrative claims database from the Australian Department of Veterans' Affairs. All veterans aged 65 years and over who were new users of warfarin were followed until death or study end. Risk of bleeding was assessed using a Poisson GEE model adjusting for age, gender, socioeconomic status, co-morbidity index, previous bleeding related hospitalisations and indicators of health service use. Overall, 17661 veterans who used warfarin at any time during the study period were included. The overall incidence rate of bleeding-related hospitalisations was 4.1 (95% CI 3.7-4.6) per 100 person-years in veterans who were not receiving potentially interacting medicines. Bleeding-related hospitalisation rates were significantly increased when warfarin was co-prescribed with low-dose aspirin (Adjusted rate ratio (AdjRR) 1.44, 95% CI 1.00-2.07), clopidogrel (AdjRR 2.23, 95% CI 1.48–3.36), clopidogrel with aspirin (AdjRR 3.44, 95% CI 1.28-9.23), amiodarone (AdjRR 3.33, 95% CI 1.38–8.00) and antibiotics (AdjRR 2.34, 95% CI 1.55-3.54). Models assessing bleeding risk with warfarin should take account of the range of potentially harmful medicine combinations used in elderly people with comorbid conditions.

Short‐term warfarin reversal for elective surgery – using low‐dose intravenous vitamin K: safe, reliable and convenient*

Peri-procedural management of warfarin reflects an intricate balance between the restoration of haemostasis and appropriate thromboprophylaxis. This prospective single-arm study assessed the safety and efficacy of a convenient schedule, incorporating low-dose intravenous vitamin K (vitK(IV) ) for short-term warfarin reversal prior to elective surgery, as well as vitK-dependent factor levels (vitK-Factors) and International Normalized Ratio (INR) pre- and post-vitK(IV) . One seventy eight patients on long-term warfarin received 3mg vitK(IV) 12-18 h pre-procedure with no adverse reactions. 167/178 (94%) achieved an INR≤1·5 post-vitK(IV) on the day of surgery, while all achieved INR≤1·7. Four patients had procedure-associated major bleeding, but importantly had achieved a pre-procedure INR<1·5 and vitK-Factors >0·30iu/ml. No patient suffered a symptomatic thromboembolism during the 6-week follow-up. Median days to re-establish a therapeutic INR were 4 (range 2-11). VitK(IV) near normalized all vitK-Factors, with a uniform pattern of depletion and repletion in association with an increase and decrease in INR, respectively; and from the data, INR<1·5 correlated with vitK-Factors >0·30iu/ml. Low-dose vitK(IV) for short-term warfarin reversal was reliable and safe, and successfully lowered the INR to an acceptable level for planned surgery, with no excess of bleeding, thromboembolism, delayed discharge, or resistance to warfarin. The protocol was simple and convenient for both the patients and the healthcare institution.