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Interruption of chronic anticoagulation due to the bleeding risk associated with an elective procedure may also lead to an elevated risk of thromboembolism. Periprocedural bridging with either unfractionated heparin or low-molecular weight heparin had been the mainstay of therapy for many patients receiving chronic warfarin treatment based on an estimation of a patient's thromboembolic risk. However, recent results from cohort studies and placebo-controlled randomized trials in the periprocedural use of heparin bridging for warfarin-treated patients reveal a consistent two- to three-fold increase in the risk of major bleeding and no benefit in terms of a reduction in the risk of stroke and systemic embolism. The most recent antithrombotic guidance statements suggest that the majority of patients on chronic warfarin, except those at high risk of thromboembolism, may safely interrupt and resume warfarin without heparin bridging in elective periprocedural settings. In addition, data from the use of heparin bridging in patients on direct oral anticoagulants during temporary interruption for an elective procedure also reveal harm and no benefits of this approach. A strategy that considers the pharmacokinetic properties of the direct oral anticoagulants, the bleeding risk of each procedure, and patient renal function would safely obviate the need for heparin bridging. In this review, the authors summarize the major studies of heparin bridging for patients on chronic oral anticoagulants that may lead to a change in practice in periprocedural antithrombotic management and define an evidence-based heparin bridging protocol for those patient groups who may be the candidates for this approach., Competing Interests: A.C.S. reports grants and personal fees from Janssen and Boehringer Ingelheim, personal fees from Bayer and ATLAS ARO Group, outside the submitted work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Anticoagulation Management Services (AMS) are known to improve warfarin management in the outpatient setting. The guideline recommendations are well established and indicate that patients who receive a Vitamin K antagonist (VKA) should be under the care of an experienced and specialized anticoagulation clinic (Lip et al. in Chest 154(5):1121-1201, 2018). Warfarin, a VKA, is considered a high risk medication and one of the most common causes of adverse events with poor patient outcomes. Anticoagulation care is assessed by measuring the percent of Time in Therapeutic Range (TTR) in patients receiving a VKA. Evidence shows that a 10% improvement in TTR has been associated with a 10% reduction in adverse event rates. Optimal management over usual medical care should prevent 7 myocardial infarctions, strokes, major bleeds, or deaths per 100 patients/year (Bussey et al. in Pharmacotherapy 9(4):214-219, 1989). Telehealth or telemedicine can be defined as the use of electronic information along with telecommunication technologies to provide medical services to individuals that are in remote locations from each other (Perednia in JAMA 273(6):483-488, 1995; Gray et al in J Thromb Thrombolysis 2019(48):690-693, 2019). This technology allows a provider located at a distant site to use two-way audio visual electronic communication to deliver clinical health care services to a patient who is located at an originating site (Kristian et al. Int J Technol Assess Health Care 28(1):44-51, 2012; Testa and Zimmermann in Telemedicine for managing patients on oral anticoagulant, 2011; Telehealth Services in CMS Manual System Pub 100-04 medicare claims processing, 2019). The goals of the Telehealth Anticoagulation Management Service are to: (1) increase patient satisfaction (2) reduce turnaround time for results by providing the INR (International Normal Ratio) results in real time (3) increase patient compliance to INR testing and (4) improve system wide anticoagulation care by increasing cTTR (center Time in Therapeutic Range) metrics to high quality metrics of 65% and above. The overarching goal of our health system Telehealth program was to develop a collaborative care telemedicine INR model in collaboration with core laboratories (Patient Service Centers or PSCs) in order to improve patient quality metrics on warfarin. In this model, the Tele-ACTS Center (Telehealth Anticoagulation and Clinical Thrombosis Service) team was able to provide distant care for the outpatient population on warfarin maintenance therapy using a virtual telemedicine INR model located in a distant location to the PSC. Using this model, we were able to improve center-based TTR by 45.73%.

This study evaluates three warfarin dosing algorithms (Kimmel, Dawson, High Dose ≥ 2.5 mg) for hospitalized older adults. A random selection of 250 patients with overshoots (INR ≥ 5 after 48 h of hospitalization) and 250 patients without overshoots were accessed from a database of 12,107 inpatients ≥ 65 years treated with chronic warfarin during hospitalization between January 1, 2014 and June 30, 2016. Algorithms were retrospectively applied to patients 2 days prior to overshoots in the overshoot group, and 2 days prior to the maximum INR reached after 48 h of hospitalization in the non-overshoot group. Patients were categorized as overdosed or not overdosed and compared using descriptive statistics. Logistic regression modeling determined predictors for overshoots. There was no significant difference between overdose and non-overdose groups for progressing to overshoots by the Kimmel (51.0% vs. 48.7%, p = 0.67) or Dawson (48.5 vs. 57.9%, p = 0.19) algorithms. The Low Dose Group (≤ 2.5 mg) was significantly more likely to experience an overshoot than the High Dose Group (56.6% vs. 45.5%, p = 0.04). The Low Dose Group was more likely to be older (81.4% vs. 71.1%, p = 0.02), female (63.5% vs. 49.8%, p = 0.02), weigh less (71.3 ± 21.9 vs. 79 ± 23.1, p = 0.002), and be prescribed amiodarone (16.6% vs. 8.1%, p = 0.01). While none of the algorithms predicted overshoots in logistic regression modeling, weight over 70 kg and black race remained protective. The High Dose Algorithm revealed that providers appropriately gave lower doses to patients at highest risk for warfarin sensitivity. Future studies are needed to investigate tools for inpatient warfarin dosing in older adults.

Introduction: Limited data exist on direct-acting oral anticoagulants in morbidly obese patients with venous thromboembolism (VTE). We compared clinical and health/economic outcomes with rivaroxaban versus warfarin for VTE treatment in morbidly obese patients., Materials and Methods: This retrospective 1:1 propensity score matched cohort study analyzed data from 2 US claims databases. VTE patients initiating rivaroxaban or warfarin were identified who had diagnosis codes for morbid obesity (ICD-9:278.01,V85.4; ICD-10:E66.01,E66.2,Z68.4) 12 months pre- or 3 months post-initiation and followed ≥3 months. Intent-to-treat (ITT) and on-treatment (OT) analyses were conducted using conditional logistic regression and generalized linear models to compare recurrent VTE and major bleeding risks, healthcare resource utilization (HRU), and per patient per year (PPPY) costs., Results: In total, 2890 matched pairs of morbidly obese VTE patients initiating rivaroxaban or warfarin were identified. Risks of recurrent VTE (ITT: OR: 0.99; 95% CI: 0.85-1.14) and major bleeding (OT: OR: 0.75; 95% CI: 0.47-1.19) were similar for cohorts. Anti-Factor Xa laboratory measurement was performed on <1% of rivaroxaban cohort. Hospitalizations (OR: 0.86; 95% CI: 0.77-0.96) and outpatient visits (OR: 0.23; 95% CI: 0.10-0.56), were lower with rivaroxaban versus warfarin (ITT analysis). Average total medical costs PPPY were $2829 lower with rivaroxaban versus warfarin ($34,824 vs $37,653), mainly driven by hospitalization costs. Total healthcare costs (including pharmacy) were similar ($43,034 vs $44,565)., Conclusions: Morbidly obese VTE patients receiving rivaroxaban had similar risks of recurrent VTE and major bleeding versus warfarin. Rivaroxaban treatment yielded significantly less HRU and total medical costs, with similar total healthcare costs between groups., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Achieving therapeutic international normalized ratio (INRs) in warfarin naïve older adults can be complicated due to sensitivity factors. While multiple tools exist for warfarin initiation in the outpatient setting, there is a dearth of guidance for inpatient initiation. This study aims to: (1) describe a large health system's initiation warfarin quality metrics in older inpatients, defined by INR overshoots greater than or equal to 5.0; (2) identify intrinsic and extrinsic patient factors associated with overshoots; and (3) explore the association between inpatient overshoots and clinical outcomes. Data on inpatients ≥ 65 years initiated on warfarin 1/1/2014-6/30/2016 were extracted through retrospective chart review. The primary outcome was prevalence of overshoots (INR ≥ 5). Logistic regression modeling determined the risk factors for overshoots. Multivariate analysis was employed to associate overshoots with length of stay (LOS), bleeding, and mortality. Additional analysis of the impact of patient weight (kg) on overshoots was achieved through chi square analysis. Of 4556 inpatients initiated on warfarin, 8% experienced overshoots. Non-black race, peripheral vascular disease, chronic obstructive pulmonary disease (COPD), mild liver disease, low weight, and no statin use were found to be predictive of overshoots. Compared to the group without overshoots, the group with overshoots experienced a significantly increased LOS (13 days vs. 8 days, < 0.001), higher bleed rate (30.1% vs. 6.5%, adjusted OR 6.2, p < 0.001), and higher mortality rate (13.8% vs. 3.4%, adjusted OR 4.4, p < 0.001). Inpatient warfarin initiation was associated with frequent overshoots and poor outcomes. Future studies should focus on strategies to improve hospital warfarin initiation safety.

Background: There are limited data regarding clinical outcomes and healthcare resource utilization of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) who are morbidly obese (body mass index >40 kg/m 2 or body weight >120 kg)., Methods: Using data from 2 US healthcare claims databases, we identified patients initiating rivaroxaban or warfarin who had ≥1 medical claim with an AF diagnosis, a diagnostic code for morbid obesity (ICD-9: 278.01, V85.4%; ICD-10: E66.01%, E66.2%, Z68.4%), and a minimum continuous enrollment of 12 months before and 3 months after treatment initiation. Patients were excluded if they had mitral stenosis, a mechanical heart valve procedure, an organ/tissue transplant, or an oral anticoagulant prescription prior to the index date. Rivaroxaban and warfarin patients were 1:1 propensity score matched. Conditional logistic regression was used to compare ischemic stroke/systemic embolism and major bleeding risk. Generalized linear models were used to compare healthcare resource utilization and costs., Results: A total of 3563 matched pairs of morbidly obese AF patients treated with rivaroxaban or warfarin were identified. The majority (81.4%) of patients in the rivaroxaban cohort were receiving the 20 mg dose. The rivaroxaban and warfarin cohorts were well balanced after propensity score matching. The risks of ischemic stroke/systemic embolism and major bleeding were similar for rivaroxaban and warfarin users (stroke/systemic embolism: 1.5% vs 1.7%; odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.60, 1.28; P = .5028; major bleeding: 2.2% vs 2.7%; OR: 0.80; 95% CI: 0.59, 1.08; P = .1447). Total healthcare costs including medication costs per patient per year (PPPY) were significantly lower with rivaroxaban versus warfarin ($48,552 vs $52,418; P = .0025), which was primarily driven by lower hospitalization rate (50.2% vs 54.1%; P = .0008), shorter length of stay (7.5 vs 9.1 days; P = .0010), and less outpatient service utilization (86 vs 115 visits PPPY; P < .0001)., Conclusions: Morbidly obese AF patients treated with rivaroxaban had comparable risk of ischemic stroke/systemic embolism and major bleeding as those treated with warfarin, but lower healthcare resource utilization and costs., (Copyright © 2019 Janssen Scientific Affairs, LLC. Published by Elsevier Inc. All rights reserved.)

Background: Direct oral anticoagulants (DOACs) are surpassing warfarin as the anticoagulant of choice for stroke prevention in nonvalvular atrial fibrillation. DOAC outcomes in elective periprocedural settings have not been well elucidated and remain a source of concern for clinicians. The aim of this meta-analysis was to evaluate the periprocedural safety and efficacy of DOACs versus warfarin in patients with nonvalvular atrial fibrillation., Methods: We reviewed the literature for data from phase III randomized controlled trials comparing DOACs with warfarin in the periprocedural period among patients with nonvalvular atrial fibrillation. Substudies from 4 trials (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation], and ENGAGE-AF [Effective Anticoagulation With Factor xA Next Generation in Atrial Fibrillation]) were included in the meta-analysis. DOACs as a group and warfarin were compared in terms of the 30-day pooled risk for stroke/systemic embolism, major bleeding, and death, according to whether the study drug was interrupted or not periprocedurally. The overall relative risk (RR) was estimated with a random-effects model. The I 2 test was used to assess heterogeneity in RR among the studies., Results: In the uninterrupted anticoagulant strategy, there were no differences in the rates of stroke/systemic embolism (pooled risk, 0.6% [29 events/4519 procedures] versus 1.1% [31/2971]; RR, 0.70; 95% confidence interval [CI], 0.41-1.18) and death (1.4% versus 1.8%; RR, 0.77; 95% CI, 0.53-1.12) between DOACs and warfarin and significantly fewer major bleeding events (2.0% versus 3.3%; RR, 0.62; 95% CI, 0.47-0.82) with DOACs compared to warfarin. Under an interrupted strategy, there was no significant difference between DOACs versus warfarin for stroke/systemic embolism (0.4% [41/9260] versus 0.5% [31/7168]; RR, 0.95; 95% CI, 0.59-1.55), major bleeding (2.1% versus 2.0%; RR, 1.05; 95% CI, 0.85-1.30), and death (0.7% versus 0.6%; RR, 1.24; 95% CI, 0.76-2.04). The studies were homogeneous ( I 2 =0.0%) for all calculated pooled associations except for the RR of death in the interrupted strategy ( I 2 =26.3%)., Conclusions: The short-term safety and efficacy of DOACs and warfarin are not different in patients with nonvalvular atrial fibrillation periprocedurally. Under an uninterrupted anticoagulation strategy, DOACs are associated with a 38% lower risk of major bleeding compared with warfarin.

Postthrombotic syndrome (PTS) is a frequent complication of venous thromboembolism (VTE). Using MarketScan claims data from January 2012 to June 2015, we identified adults with a primary diagnosis code for VTE during a hospitalization/emergency department visit, ≥6 months of insurance coverage prior to the index event and newly started on rivaroxaban or warfarin within 30 days of the index VTE. Patients with <4-month follow-up postindex event or a claim for any anticoagulant during 6-month baseline period were excluded. Differences in baseline characteristics between rivaroxaban and warfarin users were adjusted for using inverse probability of treatment weights based on propensity scores. Patients were followed for the development of PTS starting 3 months after the index VTE. Cox regression was performed and reported as hazard ratios with 95% confidence intervals (CIs). In total, 10 463 rivaroxaban and 26 494 warfarin users were followed for a mean of 16 ± 9 (range, 4-39) months. Duration of anticoagulation was similar between cohorts (median = 6 months). Rivaroxaban was associated with a 23% (95% CI: 16-30) reduced hazard of PTS versus warfarin. Rivaroxaban was associated with a significant risk reduction in symptoms of PTS compared to warfarin in patients with VTE treated in routine practice.

Background: There is concern about the management of anticoagulated patients with atrial fibrillation (AF) who require an urgent surgery/procedure, especially in those who are receiving a direct oral anticoagulant such as dabigatran., Methods: We accessed the database from RE-LY, a randomized trial comparing dabigatran (110mg and 150mg twice daily) with warfarin for stroke prevention in AF, to assess patients who had an urgent and elective surgery/procedure. We compared the risk for thromboembolism, major bleeding and mortality according to treatment allocation (dabigatran 110mg or 150mg, or warfarin) or surgery/procedure type (urgent or elective). Outcomes were assessed from day-7 to day 30 after a surgery/procedure., Results: 353 patients (2.0% of study population) had an urgent surgery/procedure and 4168 patients (23.1% of study population) had an elective surgery/procedure. In patients on dabigatran 110mg, dabigatran 150mg and warfarin who had an urgent surgery/procedure: rates of thromboembolism were 16.1%, 7.4%, and 10.5%; rates of major bleeding were 17.0%, 17.6%, and 22.9%; rates of mortality were 6.3%, 1.5%, and 2.9%, respectively (P>0.50 for all comparisons). Rates of these outcomes were multi-fold higher in patients having an urgent rather than an elective surgery/procedure (P<0.5 for all comparisons)., Conclusion: In anticoagulated patients with atrial fibrillation who require an urgent surgery/procedure, the risks for thromboembolism, major bleeding and mortality did not differ depending on treatment with dabigatran or warfarin, but rates of these outcomes were multi-fold higher than in patients having an elective surgery/procedure., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In patients with atrial fibrillation (AF) who require interruption of dabigatran or warfarin for an elective surgery/procedure, the risks and benefits of perioperative bridging anticoagulation is uncertain.We accessed the database from RE-LY, a randomised trial comparing dabigatran with warfarin for stroke prevention in AF, to assess the potential benefits and risks of bridging. In patients who had a first interruption of dabigatran or warfarin for an elective surgery/procedure, we compared the risk for major bleeding (MB), stroke or systemic embolism (SSE) and any thromboembolism (TE) in patients who were bridged or not bridged during the period of seven days before until 30 days after surgery/procedure. We used multivariable Cox regression to adjust for potential confounders.Bridging was used more during warfarin interruption than dabigatran interruption (27.5 % vs 15.4 %; p< 0.001). With dabigatran interruption, bridged patients had more MB (6.5 % vs 1.8 %, p< 0.001) than those not bridged but bridged and not bridged groups did not differ for any TE (1.2 % vs 0.6 %, p=0.16) and SSE (0.5 % vs 0.3 %, p=0.46). With warfarin interruption, bridged patients had more MB (6.8 % vs 1.6 %, p< 0.001) and any TE (1.8 % vs 0.3 %, p=0.007) than those not bridged but bridged and not bridged groups did not differ for SSE (0.5 % vs 0.2 %, p=0.321). In conclusion, in patients who interrupted dabigatran or warfarin for a surgery/ procedure in the RE-LY trial, use of bridging anticoagulation appeared to increase the risk for major bleeding irrespective of dabigatran or warfarin interruption.

Background: During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI., Methods and Results: In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non-central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3-30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36-1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80-2.00]; P=0.32)., Conclusions: TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Excellent control of the international normalised ratio (INR) is associated with improved clinical outcomes in patients receiving warfarin, and can be achieved by anticoagulation clinics but is difficult in general practice. Anticoagulation clinics have often used validated commercial computer systems to manage the INR, but these are not usually available to general practitioners. It was the objective of this study to perform a randomised trial of a simple one-step warfarin dosing algorithm against a widely used computerised dosing system. During the period of introduction of a commercial computerised warfarin dosing system (DAWN AC) to an anticoagulation clinic, patients were randomised to have warfarin dose adjustment done according to recommendations of the existing warfarin dosing algorithm or to those of the computerised system. The study tested if the computerised system was non-inferior to the existing algorithm for the primary outcome of time in therapeutic INR range of 2.0-3.0 (TTR), with a one-sided non-inferiority margin of 4.5%. There were 541 patients randomised to commercial computerised system and 527 to the algorithm. Median follow-up was 159 days. A dose recommendation was provided and followed in 91% of occasions for the computerised system and in 90% for the algorithm (p=0.03). The mean TTR was 71.0% (standard deviation [SD] 23.2) for the computerised system and 71.9% (SD 22.9) for the algorithm (difference 0.9% [95% confidence interval: -1.4% to 4.1%]; p-value for non-inferiority=0.002; p-value for superiority=0.34). In conclusion, similar maintenance control of the INR was achieved with a simple one-step dosing algorithm and a commercial computerised management system.

The periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of high-quality evidence to inform best practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the use of heparin bridging therapy, to minimize time off anticoagulant therapy, while the procedural bleed risk determines how and when postprocedural anticoagulant therapy should be resumed. Warfarin should be continued in patients undergoing selected minor procedures, whereas in major procedures that necessitate warfarin interruption, heparin bridging therapy should be considered in patients at high thromboembolic risk and in a minority of patients at moderate risk. Periprocedural data with the novel oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, are emerging, but their relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use. This review aims to provide a practical, clinician-focused approach to periprocedural anticoagulant management.

Purpose of Review: Patients undergoing oral anticoagulation treatment with vitamin K antagonist (VKA) therapy are at a high risk of bleeding when undergoing an invasive surgery or procedure. Bridging therapy with parenteral heparin, usually at therapeutic doses, aims to protect these patients against thromboembolism during temporary periprocedural interruption of VKA therapy. Whether or not to interrupt VKA therapy and initiate bridging therapy is a difficult decision that is based upon both the patient's and the procedure's thromboembolic and bleeding risks., Recent Findings: There are minor procedures that can safely be done without the need for VKA interruption. Patient groups that may benefit from bridging therapy during temporary VKA interruption for a procedure include those who are at moderate-to-high risk of thromboembolism. Procedural bleed risk should determine when to resume bridging and VKA therapies. Recent findings highlight that low-molecular-weight heparin, usually in the outpatient setting, is the preferred agent over intravenous unfractionated heparin for bridging therapy, which includes patients with prosthetic heart valve indications for VKA therapy., Summary: Large, recently initiated placebo-controlled trials in bridging therapy are discussed, as well as future alternatives to VKA therapy in oral anticoagulation during the periprocedural period.

This multicenter, prospective, open label, observational study evaluated practice patterns of physicians using tinzaparin, a low-molecular-weight heparin (LMWH), and warfarin for the treatment of deep venous thrombosis (DVT) with or without pulmonary embolism (PE). Short-term recurrence of venous thromboembolism (VTE) and safety were also evaluated. Patients with an objective diagnosis of DVT, with or without PE, were invited by their physician to participate in this study. Treatment was given according to the approved U.S. package inserts for tinzaparin (175 IU/kg SQ QD) and warfarin and the clinical judgment of the prescribing physician. Baseline patient history including demographic information and the results of tests to confirm the diagnosis of DVT, with or without PE, were collected. Follow-up information included the treatment setting in which each dose of tinzaparin was administered, medical training of the person administering tinzaparin doses, timing of initiation of warfarin with respect to that of tinzaparin, length of overlap of tinzaparin and warfarin therapy, and adverse experiences. A total of 334 patients were enrolled at 65 sites. Patients across a wide age (range 18-93 years old) and body weight (range 40-261 kg) were included. Overall, 27.3% of patients had cancer, and 50% of the overall study population reported more than one VTE risk factor. Mean duration of tinzaparin treatment was 7.61 days. Therapy at home was more common in suburban and rural settings than in urban settings. High proportions of patient, even among the small group with concurrent PE, were treated at home with self-injection. Severity of disease was the primary reason for hospitalization. Home treatment of DVT, with or without PE, with self administration of tinzaparin at 175 IU SQ once-daily was safe and resulted in an acceptably low rate of recurrent venous thromboembolism and adverse events. Home therapy in the usual practice setting should achieve substantial overall cost savings in the treatment of DVT.

The management of patients on chronic oral anticoagulant therapy, namely Vitamin K antagonists such as warfarin, is often associated with difficult and challenging issues for the healthcare practitioner. Many of these issues, such as warfarin failure or resistance, the optimal warfarin initiation dose, the optimal target International Normalized Ratio in antiphospholipid syndrome, the optimal monitoring frequency and use of point-of-care monitoring, the management of oral anticoagulation during invasive procedures, and the management of over-anticoagulation, have not been evaluated in rigorously-designed clinical trials. The latest American College of Chest Physician recommendations concerning these issues are Grade 2C, the weakest recommendations available. It remains up to the experience and expertise of the individual practitioner along with whatever clinical evidence is available in a particular healthcare environment-especially one associated with an anticoagulant management service-to implement management strategies with respect to these issues in patients on oral anticoagulation.

Objective: The objectives of this study were to observe a commercially insured sample diagnosed with a venous thromboembolism (VTE) event and treated postevent with warfarin and to detail the thromboembolic and bleeding outcomes in the time periods during warfarin therapy and after discontinuation of such therapy., Methods: This retrospective, observational cohort study used medical, pharmacy, and eligibility data from 2 US health plans. Study inclusion required an inpatient diagnosis of deep venous thrombosis (DVT) or pulmonary embolism (PE) between January 1, 1998, and December 31, 2000; warfarin, heparin, or low-molecular-weight heparin within 30 days after diagnosis; no VTE diagnosis; and no anticoagulant use for 3 months preceding diagnosis. A random sample of medical charts was abstracted to validate VTE events and collect prothrombin time/international normalized ratio (INR) result data. Recurrent VTE events, bleeding events, and proportion of time within INR range were captured in the postindex VTE event time period. Univariate and multivariate statistical techniques were used to assess outcomes., Results: A total of 2,090 patients were identified with a newly diagnosed VTE event (DVT only, 1450; PE with or without DVT, 640). Mean (SD) age was 61.7 (16) years; mean (SD) follow-up time after the index diagnosis was 21.3 (10) months. Overall mean (SD) length of warfarin therapy was 6.6 (6) months. During the follow-up period, 224 patients (10.7%) experienced a recurrent VTE event and 122 patients (5.8%) experienced a bleeding event requiring hospitalization. The cumulative incidence of recurrent VTE events over 3 and 6 months was 9.0% and 10.9%, respectively. Using the chart abstraction subset, patients were within the appropriate INR range 37.7% of the time while receiving warfarin., Conclusions: Negative outcomes associated with warfarin therapy-recurrent VTE events and bleeding requiring hospitalization-were experienced by 10.7% and 5.8% of patients, respectively. These data suggest that negative outcomes may be more prevalent in usual community medical practice compared with rates observed in the controlled environment of the clinical trial or specialized anticoagulation clinic.

Study Objectives: There have been no health-care cost evaluations comparing the use of low-molecular-weight heparin (LMWH) to unfractionated heparin (UH) as "bridge therapy" in the perioperative period in patients receiving long-term oral anticoagulant (OAC) therapy who need interruption of therapy to undergo an elective surgical procedure. We performed a retrospective analysis of the medical and administrative records of health plan members in a managed care organization who underwent bridge therapy perioperatively with either i.v. UH, administered in a hospital setting, or LMWH, administered primarily in the outpatient setting using disease management guidelines., Design: A retrospective analysis of medical and administrative records of treated health plan members meeting inclusion/exclusion criteria during the two study periods (ie, from 1994 to 1996 and from 1998 to 2000)., Setting: Staff-model health maintenance organization serving New Mexico., Patients: The UH group included persons receiving long-term warfarin therapy from 1994 to 1996 (26 patients), and the LMWH group included persons receiving long-term warfarin therapy from 1998 to 2000 (40 patients) with perioperative use of heparin (either UH or LMWH) as bridge therapy for an elective surgical procedure., Interventions: Costs were calculated for the period from 10 days before the procedure through 30 days after the procedure. The rates of adverse events (ie, valvular or mural thrombus, intracranial event, transient ischemic attack, peripheral arterial event, venous thromboembolic event, major and minor bleeding, thrombocytopenia, and death) occurring 1 to 30 days postprocedure were determined., Measurements and Results: The groups were similar in age, sex, Charlson score, indication for long-term warfarin therapy (ie, arterial/cardiac vs venous), mean international normalized ratio prior to procedure, procedure duration, use of intraprocedural anticoagulant agents or thrombolytic agents, and use of general anesthesia during the procedure (all p > 0.05). A total of 34.6% of UH patients and 40.0% of LMWH patients experienced one or more clinical adverse events within 30 days of the postoperative period, a difference that was not statistically significant (p = 0.67). The mean total health-care costs were 31,625 dollars in the UH group and 18,511 dollars in the LMWH group (p < 0.01). The mean inpatient costs were 28,515 dollars in the UH group and 14,330 dollars in the LMWH group (p < 0.01). Outpatient surgery costs (1,159 dollars vs 53 dollars, respectively; p = 0.01) and pharmacy costs (639 dollars vs 133 dollars, respectively; p < 0.01) were higher in the LMWH group., Conclusions: The mean total health-care costs in the perioperative period were significantly lower (by 13,114 dollars) in patients receiving long-term OAC therapy using LMWH compared to those receiving it using UH for an elective surgical procedure. The cost savings associated with LMWH use were accomplished through the avoidance or minimization of inpatient stays and no increase in the overall rate of clinical adverse events in the postoperative period.

Purple toes syndrome is an extremely uncommon, nonhemorrhagic, cutaneous complication associated with warfarin therapy. It is characterized by the sudden appearance of bilateral, painful, purple lesions on the toes and sides of the feet that blanch with pressure. The syndrome usually develops 3-8 weeks after the start of warfarin therapy. A 47-year-old man with a history of purple toes syndrome that resolved after discontinuing warfarin--prescribed for a deep vein thrombosis (DVT) in his right lower leg--experienced an acute, proximal DVT in his other leg. Warfarin again was prescribed; 1 week later, purple toes syndrome developed in that extremity. Warfarin therapy again was discontinued, and intravenous unfractionated heparin was started; the patient's clinical picture indicated a possible pulmonary embolism, and laboratory analysis suggested antiphospholipid syndrome. The patient's toe pain resolved, but the purple discoloration persisted. Follow-up laboratory analysis confirmed antiphospholipid syndrome, and warfarin was restarted with close monitoring. No further complications occurred with long-term therapy. Although a rare complication of therapy, clinicians should monitor for the development of purple toes syndrome in patients taking warfarin.

A 71-year-old woman experienced a pruritic, maculopapular, morbilliform rash on her lower extremities 5 days after starting warfarin for recurrent deep vein thrombosis. The rash extended to her truncal areas and progressively worsened until somewhat painful vesicular lesions developed. Warfarin was discontinued, and subcutaneous injections of enoxaparin were begun; the rash resolved. In addition to a history of deep vein thrombosis, the patient had experienced a hypersensitivity skin reaction to warfarin in the past that necessitated withdrawal of the drug and placement of a vena caval filter. Because no clear consensus exists on whether dyes used in compounding warfarin play a causative role or whether allergic cross-sensitivity occurs among the coumarin derivatives, the patient was rechallenged with a dye-free warfarin 10-mg tablet. The pruritic rash returned along with the vesicular lesions and continued to worsen until the warfarin was discontinued again. The patient subsequently was given oral anticoagulant therapy with anisindione, an indanedione, and her symptoms resolved completely. Health care providers managing patients who are receiving oral anticoagulant therapy should be aware of the maculopapular allergic reactions associated with warfarin and consider alternative treatment options such as anisindione.

Appropriate perioperative management of patients on chronic oral anticoagulation (OAC)—including warfarin and the direct oral anticoagulants—is a poorly defined yet important clinical issue with potentially severe consequences in the postoperative period. We sought to prospectively evaluate the effect of the Management of Anticoagulation in the Periprocedural Period (MAPPP) mobile app as a clinical decision tool in the management of patients on chronic OAC undergoing elective procedures or surgeries. Between January 1, 2018, and January 31, 2019, 642 patients treated in our health system were included. Eligible patients met the following criteria: age >18 years old, creatinine clearance ≥15 mL/min, and on chronic OAC with adequate information regarding baseline characteristics. Our study outcome was patient's emergency department (ED) visits within 30 days postprocedure. The MAPPP app was integrated into the electronic health record (EHR), and the end user was free to accept or decline recommended evidence-based perioperative anticoagulation management guidance. Analysis revealed that acceptance was more common in younger patients (P =.0137), patients on oral anticoagulants other than warfarin (P <.0001), and patients undergoing increased bleeding risk procedures (P =.0068). Acceptance of the MAPPP app recommendation was significantly associated with fewer ED visits (acceptance group: 4.0% vs rejection group: 8.3%, P =.0205). Logistic regression showed that intervention acceptance and female gender were significantly associated with fewer—while age ≥80 with more—30-day ED visits. Our findings indicate that newer technologies, such as the MAPPP app, integrated into clinical EHR workflow, can significantly augment evidence-based perioperative anticoagulation management and potentially result in a reduction of adverse outcomes. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are a relatively recent addition to the oral anticoagulant armamentarium, and provide an alternative to the use of vitamin K antagonists such as warfarin. Regardless of the type of agent used, bleeding is the major complication of anticoagulant therapy. The decision to restart oral anticoagulation following a major hemorrhage in a previously anticoagulated patient is supported largely by retrospective studies rather than randomized clinical trials (mostly with vitamin K antagonists), and remains an issue of individualized clinical assessment: the patient's risk of thromboembolism must be balanced with the risk of recurrent major bleeding. This review provides guidance for clinicians regarding if and when a patient should be re-initiated on DOAC therapy following a major hemorrhage, based on the existing evidence. [ABSTRACT FROM AUTHOR]

In this review the authors discuss the use of oral and parenteral anticoagulants for the prevention and treatment of venous thromboembolism (VTE) in the elderly. The use of anticoagulant agents in VTE prophylaxis and treatment in the elderly is complicated by an increase with age in the presence of multiple risk factors and co-morbidities that may increase the risk of both VTE and bleeding. Age itself is identified as an independent risk factor for thromboembolism. VTE is underdiagnosed in the elderly population, and routine prophylaxis frequently falls short of the levels required according to level of risk. Although appropriate anticoagulation of at-risk patients offers a means of reducing the significant VTE burden in this population, concerns have been raised over the use of anticoagulants in a patient group in whom multiple risk factors are common. Bleeding in the elderly can be exacerbated by reduced renal clearance and hypersensitivity to oral anticoagulants that may lead to over-anticoagulation. Although bleeding due to anticoagulant therapy is a serious issue in the elderly, it is often overemphasised, given the therapeutic value otherwise observed in treating this patient group. Warfarin is still used in VTE prophylaxis after orthopaedic surgery and for long-term VTE treatment. Unfractionated and low-molecular-weight heparins (LMWHs) have been shown to be safe and effective in the prophylaxis of VTE, and are now being shown to be as effective as warfarin in the initial and long-term treatment of VTE. LMWHs confer the advantage over unfractionated heparin of subcutaneous once-daily administration with no requirement for laboratory monitoring of their anticoagulant effect, which allows for the convenience of outpatient therapy. New anticoagulants that may be of potential benefit in this patient population include fondaparinux sodium, but clinical experience of this drug in the elderly remains limited. [ABSTRACT FROM AUTHOR]

Study Objective. Traditional perioperative bridge therapy for patients receiving long-term oral anticoagulation involves weight-adjusted intravenous unfractionated heparin (UFH) in the perioperative period during temporary discontinuation of the oral anticoagulant. We sought to determine whether art alternate strategy of outpatient-based perioperative disease management with low-molecular-wright heparin (LMWH) as bridge therapy provides the potential for cost savings. Design. Retrospective review of all clinic notes from an anticoagulation clinic. Setting. An integrated, staff-model health maintenance organization. Patients. Patients receiving long-term warfarin therapy from January 1998-March 2002 who received perioperative bridge therapy with the LMWH enoxaparin 1 mg/kg twice/day subcutaneously. Measurements and Main Results. A total of 126 bridge therapy encounters in 84 patients receiving LMWH as perioperative bridge therapy were identified, with 48 of those encounters involving patients with at least one mechanical heart valve. A total of 1108 hospital bed days were saved. Based on 1996 cost estimates, the total approximate cost savings for the 4.25 years of the outpatient bridge therapy program was $903,020. No thrombotic events were reported. Three major hemorrhagic events that required discontinuation of LMWH were reported, Conclusion. Outpatient-based disease management protocols and the LMWH enoxaparin as bridge therapy during temporary discontinuation of warfarin for an elective surgical procedure resulted in cost savings of approximately $212.475/year in an integrated health maintenance organization. In addition, this strategy appears both safe and effective. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are a relatively recent addition to the oral anticoagulant armamentarium, and provide an alternative to the use of vitamin K antagonists such as warfarin. Regardless of the type of agent used, bleeding is the major complication of anticoagulant therapy. The decision to restart oral anticoagulation following a major hemorrhage in a previously anticoagulated patient is supported largely by retrospective studies rather than randomized clinical trials (mostly with vitamin K antagonists), and remains an issue of individualized clinical assessment: the patient's risk of thromboembolism must be balanced with the risk of recurrent major bleeding. This review provides guidance for clinicians regarding if and when a patient should be re-initiated on DOAC therapy following a major hemorrhage, based on the existing evidence. [ABSTRACT FROM AUTHOR]

The article reports on a 2015 trial on whether heparin bridging is needed during interruption of warfarin therapy before and after an operation in patients with atrial fibrillation. A randomized, double-blind, placebo-controlled trial on patients was performed. Based on results, forgoing bridging anticoagulation was not inferior to perioperative bridging with low-molecular-weight heparin for preventing arterial thromboembolism and reducing the risk of major bleeding.

Background--Periprocedural bridging with unfractionated heparin or low-molecular-weight heparin aims to reduce the risk of thromboembolic events in patients receiving long-term vitamin K antagonists. Optimal periprocedural anticoagulation has not been established. Methods and Results--MEDLINE, EMBASE, and Cochrane databases (2001-2010) were searched for English-language studies including patients receiving heparin bridging during interruption of vitamin K antagonists for elective procedures. Data were independently collected by 2 investigators (k=0.90). The final review included 34 studies with 1 randomized trial. Thromboembolic events occurred in 73 of 7118 bridged patients (pooled incidence, 0.9%; 95% confidence interval [CI], 0.0.0-3.4) and 32 of 5160 nonbridged patients (pooled incidence, 0.6%; 95% CI, 0.0-1.2). There was no difference in the risk of thromboembolic events in 8 studies comparing bridged and nonbridged groups (odds ratio, 0.80; 95% CI, 0.42-1.54). Bridging was associated with an increased risk of overall bleeding in 13 studies (odds ratio, 5.40; 95% CI, 3.00-9.74) and major bleeding in 5 studies (odds ratio, 3.60; 95% CI, 1.52-8.50) comparing bridged and nonbridged patients. There was no difference in thromboembolic events (odds ratio, 0.30; 95% CI, 0.04-2.09) but an increased risk of overall bleeding (odds ratio, 2.28; 95% CI, 1.27-4.08) with full versus prophylactic/intermediate-dose low-molecular-weight heparin bridging. Low-thromboembolic-risk and/or non-vitamin K antagonist patient groups were used for comparison. Study quality was poor with heterogeneity for some analyses. Conclusions--Vitamin K antagonist-treated patients receiving periprocedural heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to nonbridged patients. Randomized trials are needed to define the role of periprocedural heparin bridging. [ABSTRACT FROM AUTHOR]

Background: Treatment for non-valvular atrial fibrillation (NVAF) is complicated among morbidly obese (MO) patients. Current ISTH guidelines do not recommend direct oral anticoagulant use (such as rivaroxaban) in MO patients (BMI >40 kg/m2 or weight of >120 kg) due to limited clinical data available. Objective: To compare the risk of ischemic stroke (IS), major bleeding (MB), healthcare resource utilization (HCRU), and costs between MO NVAF patients initiating rivaroxaban and warfarin treatment. Methods: This retrospective cohort study used combined Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental database (12/1/2010 - 12/31/2016) to identify NVAF patients newly initiating rivaroxaban or warfarin treatment. ICD-9/ICD-10 codes were used to identify MO during a minimum continuous enrollment period of 12 months before or 3 months after treatment initiation. Rivaroxaban and warfarin patients were 1:1 propensity score matched. Conditional logistic regression was used to compare IS and MB risk. Generalized linear models were used to compare HCRU and costs. Results: We identified 3,563 matched pairs of patients with NVAF and MO treated with either rivaroxaban or warfarin, mean age was 63 (± 11) years and 46% were female. Mean follow-up time was 10.3 months and 10.6 months for rivaroxaban and warfarin, respectively. Compared with warfarin patients, those treated with rivaroxaban had similar risk of ischemic stroke (1.4% vs. 1.6%, OR: 0.89, 95% CI: 0.61-1.31, p=0.5565) and major bleeding (2.2% vs. 2.7%, OR: 0.80, 95% CI: 0.59-1.08, p=0.1447). However, rivaroxaban patients had an average $3,890 lower total healthcare costs per patient per year (PPPY) than warfarin patients ($48,552 vs. $52,418, p=0.0025), mainly driven by lower hospitalization rate (50.2% vs. 54.1%, p=0.0008), shorter length of stay (7.5 vs. 9.1 days, p=0.0010), and less outpatient service utilization (86 vs. 115 encounters, p<0.0001). Conclusions: In this large study of morbidly obese NVAF patients, those treated with rivaroxaban and warfarin treatment had similar risk of ischemic stroke and major bleeding. Treatment with rivaroxaban was associated with significantly lower PPPY costs and HCRU than treatment with warfarin in this patient population. [ABSTRACT FROM AUTHOR]