Availability Of Direct Oral Anticoagulants Research Articles

Changes in Time in Therapeutic Range Within a Warfarin Anticoagulation Clinic Following Introduction of Direct Oral Anticoagulants.

Background: As direct oral anticoagulants (DOACs) have become widely recommended as first-line anticoagulation therapy, patients who remain on warfarin are likely those unable to afford, adhere to, or utilize DOAC therapy due to the presence of a contraindication. It is currently unknown how availability of DOACs have affected populations being managed at warfarin (VKA) anticoagulation clinics. Methods: This was a retrospective chart review assessing warfarin-treated patients at an outpatient anticoagulation clinic. The primary endpoint was the 6-month time in therapeutic range (TTR) before and after DOACs were recommended as first-line therapy by clinical guidelines. Study periods were January to June 2015, before DOACs were recommended over VKA, and January to June 2022, when DOACs were often recommended over VKA. TTR, demographic changes, and the presence of contraindications to DOAC therapy in the clinic population between the two time periods were assessed. Results: No difference in 6-month TTR was observed between study periods (59% in 2015 vs 63% in 2022; P = .45). Patient demographics did not significantly vary, which may be due to the clinic retaining 45% of patients between both time periods. Contraindications to DOAC therapy were identified in 39% of the 2015 group and 49% of the 2022 group (P = .18). The most common contraindication was indication for anticoagulation. Conclusion: Availability of DOACs did not seem to significantly affect the population or management of warfarin-treated patients at an outpatient anticoagulation clinic, however, contraindications and potential challenges to use of DOAC therapy are present in many patients.

Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper.

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.

Epidemiology and outcomes of intracerebral hemorrhage associated with oral anticoagulation over 10 years in a population-based stroke registry.

Recent years have seen a change in the use of anticoagulants in the general population due to the availability of direct oral anticoagulants (DOACs) as an alternative to vitamin K antagonists (VKAs) and increased detection of atrial fibrillation. It is important to have updated epidemiological data to understand how this change is impacting on the occurrence and outcome of intracerebral hemorrhage (ICH). Our prospective population-based registry included patients with first-ever ICH occurring from January 2011 to December 2020. Oral anticoagulants (OAC)-related ICH was defined as an ICH occurring within 48 h from the intake of DOAC or VKAs, regardless of the measured international normalized ratio on hospital admission. We included 748 first-ever ICH, of whom 108 (14.4%) were OAC-related. Specifically, 75 (69.4%) ICHs occurred on VKA and 33 (30.6%) on DOAC. The incidence of oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH) was stable over time (p = 0.226). Among OAC-ICHs, we observed an increase in the overall incidence of DOAC-ICH (p for trend < 0.001) which overcome that of VKA-ICH in 2020 (incidence rate ratio (IRR) 4.71, 95% confidence interval (CI): 1.22-33.54; p = 0.022). Patients with OAC-ICH showed higher 30-day case fatality rates than those with non-OAC-ICH (48.1% vs 34.1%; p = 0.007). No changes over time were detected in the incidence of OAC-ICH, but throughout the study period, there was a change in OAC-ICH from mostly VKA-related to mostly DOAC-related. Mortality in patients with OAC-ICH was higher than in patients with non-OAC-ICH.

Trends in Use of Oral Anticoagulants in Older Adults With Newly Diagnosed Atrial Fibrillation, 2010-2020

Undertreatment of older adults with atrial fibrillation with anticoagulation therapy is an important practice gap. It has been posited that the availability of direct oral anticoagulants (DOACs) would improve oral anticoagulant (OAC) initiation in older adults with atrial fibrillation given their superior safety profile compared with warfarin. To systematically examine trends in OAC initiation and nonadherence in older adults with atrial fibrillation and coexisting geriatric conditions. This retrospective cohort study uses administrative claims data from Optum's Clinformatics Data Mart from January 1, 2010, to December 31, 2020. Participants included beneficiaries of Medicare Advantage plans aged 65 years and older with atrial fibrillation and elevated risk of ischemic stroke. Data analysis was performed from October 2021 to October 2022. Coexisting dementia, frailty, and anemia. The primary outcomes were OAC initiation within 12 months after the first diagnosis of atrial fibrillation per year and nonadherence with OAC per year (defined as <80% of proportion of days covered among patients newly started on OAC in each year). There were 21 603 to 51 236 patients per year (total for 2010-2020, 381 488 patients) in the OAC-eligible incident AF cohort (mean [SD] age, 77.2 [6.1] to 77.4 [6.8] years; 13 871 [51.8%] to 22 901 [49.8%] women). OAC initiation within 12 months after incident AF increased from 20.2% (5405 of 26 782 patients) in 2010 to 32.9% (7111 of 21 603 patients) in 2020. DOAC uptake increased from 1.1% (291 of 26 782 patients) to 30.9% (6678 of 21 603 patients), and warfarin initiation decreased from 19.1% (5114 of 26 782 patients) to 2.0% (436 of 21 603 patients). Older age (odds ratio [OR], 0.98; 95% CI, 0.98-0.98), dementia (OR, 0.57; 95% CI, 0.55-0.58), frailty (OR, 0.74; 95% CI, 0.72-0.76), and anemia (OR, 0.75; 95% CI, 0.74-0.77) were associated with lower odds of OAC initiation. During the study period, the median (IQR) proportion of days covered increased from 77.6% (41.0%-96.4%) to 90.2% (57.4%-98.6%), and OAC nonadherence decreased from 52.2% (2290 of 4389 patients) to 39.0% (3434 of 8798 patients). Since the introduction of DOACs, OAC initiation in older adults with has improved but remained suboptimal in 2020. Additional strategies are needed to improve stroke prophylaxis in all older adults with atrial fibrillation including those with coexisting dementia, frailty, and anemia.

Management of Patients at Risk for and With Left Ventricular Thrombus: A Scientific Statement From the American Heart Association.

Despite the many advances in cardiovascular medicine, decisions concerning the diagnosis, prevention, and treatment of left ventricular (LV) thrombus often remain challenging. There are only limited organizational guideline recommendations with regard to LV thrombus. Furthermore, management issues in current practice are increasingly complex, including concerns about adding oral anticoagulant therapy to dual antiplatelet therapy, the availability of direct oral anticoagulants as a potential alternative option to traditional vitamin K antagonists, and the use of diagnostic modalities such as cardiac magnetic resonance imaging, which has greater sensitivity for LV thrombus detection than echocardiography. Therefore, this American Heart Association scientific statement was commissioned with the goals of addressing 8 key clinical management questions related to LV thrombus, including the prevention and treatment after myocardial infarction, prevention and treatment in dilated cardiomyopathy, management of mural (laminated) thrombus, imaging of LV thrombus, direct oral anticoagulants as an alternative to warfarin, treatments other than oral anticoagulants for LV thrombus (eg, dual antiplatelet therapy, fibrinolysis, surgical excision), and the approach to persistent LV thrombus despite anticoagulation therapy. Practical management suggestions in the form of text, tables, and flow diagrams based on careful and critical review of actual study data as formulated by this multidisciplinary writing committee are given.

New perspectives for prevention of the post-thrombotic syndrome

While on conventional anticoagulation, up to 50% of patients with one or more episodes of proximal deep vein thrombosis (DVT) can develop post-thrombotic (PTS) manifestations. The potential strategies for PTS prevention are the treatment of acute DVT with catheter-directed thrombolysis (CDT), the use of elastic compression stockings (ECS) and that of the direct oral anticoagulants (DOAC) in place of vitamin K antagonists (VKA) for the initial and long-term treatment of DVT. Based on the results of three randomized clinical trials, CDT cannot be recommended on a routine basis because of its invasiveness, the associated risk of major bleedings and the uncertainty about its efficacy. According to the results of a placebo-controlled randomized clinical trial, ECS are no longer recommended for PTS prevention on a routine basis. However, based on the results of a recent subanalysis of a prospective cohort study, patients with residual vein thrombosis and/or popliteal valve reflux at three months are likely to benefit from ECS for at least six months. Finally, following the demonstration that the inadequacy of VKA therapy plays a key role in the PTS development, several retrospective and prospective studies have shown that the use of DOACs for the initial and long-term treatment of DVT in place of VKAs reduces the risk of PTS by approximately 50%. In conclusion, the availability of DOACs and the potential of ECS in selected patients with proximal DVT are expected to play a key role for decreasing the rate and the severity of PTS in the forthcoming years.

ASH, ABHH, ACHO, Grupo CAHT, Grupo CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panameña de Hematología, SPH, and SVH 2021 guidelines for management of venous thromboembolism in Latin America

Venous thromboembolism (VTE) is a common disease in Latin American settings. Implementing international guidelinn Aes in Latimerican settings requires additional considerations. The purpose of our study was to provide evidence-based guidelines about managing VTE for Latin American patients, clinicians, and decision makers. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)-ADOLOPMENT method to adapt recommendations from 2 American Society of Hematology (ASH) VTE guidelines (Treatment of VTE and Anticoagulation Therapy). ASH and local hematology societies formed a guideline panel comprised of medical professionals from 10 countries in Latin America. Panelists prioritized 18 questions relevant for the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context (ie, values and preferences, resources, accessibility, feasibility, and impact on health equity). The panel agreed on 17 recommendations. Compared with the original guideline, 4 recommendations changed direction and 1 changed strength. This guideline adolopment project highlighted the importance of contextualization of recommendations suggested by the changes to the original recommendations. The panel also identified 2 implementation priorities for the region: expanding the availability of home treatment and increasing the availability of direct oral anticoagulants (DOACs). The guideline panel made a conditional recommendation in favor of home treatment for individuals with deep venous thrombosis and a conditional recommendation for either home or hospital treatment for individuals with pulmonary embolism. In addition, a conditional recommendation was made in favor of DOACs over vitamin K antagonists for several populations.

The association between increasing oral anticoagulant prescribing and atrial fibrillation related stroke in Ireland.

Recent increases in the number of patients with atrial fibrillation (AF) prescribed oral anticoagulants (OAC) are evident in Ireland and internationally, largely due to the availability of direct oral anticoagulants (DOACs). This study aimed to determine the rate of stroke in the context of increasing anticoagulation utilisation, with a focus on AF-related ischaemic stroke (IS). Dispensing data for OACs were identified for the period 2010-2018 as well as hospital discharges for IS (2005-2018). Irish National Stroke Register data were used to elucidate the characteristics of patients with acute ischaemic stroke. The number of patients prescribed OACs increased by 94% from 2010-2018 with a significant change from 2013 (β = 2.57, P = .038), associated with a large increase in the number of patients on DOACs. There was 3.3-fold increase in expenditure on OACs nationally from 2013 to 2018, of which 94% was DOAC related. Using the 2013 timepoint, ischaemic stroke rates until 2018 did not show a significant deviation from the previous trend (β = 0.00, P = .898). The percentage of AF-related ischaemic stroke was stable from 2013 to 2017 with a 4.5% decrease in 2018. The percentage of ischaemic stroke patients with previously diagnosed AF decreased from 2013 to 2018; however, there was an increase in the percentage of ischaemic strokes while on OAC in this cohort. Large increases in OAC utilisation have not resulted in changes in ischaemic stroke rates at a national level. The percentage of ischaemic strokes with a previous diagnosis of AF has decreased indicating a possible benefit from greater OAC utilisation. However, the percentage presenting with an ischaemic stroke while on OAC treatment is increasing. The increase in patients presenting with stroke while treated with OAC may largely reflect the national increase in patients prescribed DOACs but the findings raise concerns about treatment failures. The real-world effectiveness of DOACs requires further examination.

Comparative Use of Direct Oral Anticoagulants and Warfarin in the Treatment of Atrial Fibrillation and Venous Thromboembolism and Prophylaxis: A Retrospective Single Center Utilization Study

IntroductionThe recent approval of direct oral anticoagulants (apixaban, dabigatran and rivaroxaban) for the risk reduction of stroke for nonvalvular atrial fibrillation, venous thromboembolism (VTE) prophylaxis and treatment opened up more choices of oral anticoagulants for the clinician to choose from, in addition to warfarin. This presents a unique opportunity to study practice trends and to examine preferred use, bleeding complications and length of stay (LOS) at a teaching hospital.MethodsThis was a retrospective single center analysis of the prescribing pattern of oral anticoagulation at Winthrop University Hospital from January 1, 2016 to June 30, 2016. Patients were identified by CareFusion Medmined Surveillance software. Inclusion criteria were > 18 years and initiated on apixaban, dabigatran, rivaroxaban, or warfarin. Exclusion criteria included oral anticoagulant change or discontinuation during hospitalization, pregnancy, and patients who were transitioned to hospice or expired during their hospital stay.The primary endpoint was to evaluate the patterns of use for oral anticoagulation. Secondary endpoints included determining the indication for anticoagulation, LOS from initiation of anticoagulation, and major bleeding events. Major bleeding events were defined by a drop in hemoglobin >2 grams/dL, or overt signs of a gastrointestinal bleed.ResultsA total of 1511 patients (apixaban 464, dabigatran 80, rivaroxaban 322 and warfarin 645) were included in this study. Patients treated with warfarin had significantly higher serum creatinine compared to all other groups. Patients treated with rivaroxaban had significantly lower serum creatinine compared to patients treated with apixaban (Table 1).There was an increasing trend towards initiating apixaban for thrombosis treatment and atrial fibrillation/flutter compared to DVT prophylaxis with warfarin (Table 3). Patients treated with rivaroxaban were more likely to have bleeding complications (151 patients, 46.9%) compared to apixaban (86, 18.5%), dabigatran (13, 16.3%) and warfarin (122, 18.9%) with p value <0.001. Patients treated with warfarin had a significantly longer LOS (5 days, 3- 8), compared to apixaban (3 days, 2 - 5), dabigatran (3 days, 2 - 6.5) and rivaroxaban (3 days, 2 - 6), p value < 0.001 (Table 2). Rivaroxaban showed decreased LOS by 20.6%, apixaban by 36.2% and dabigatran by 21.3% when compared to warfarin (Table 4). Patients >80 years had 16.18% increase in LOS compared to patients < 80 (Table 11). Post hoc analysis revealed that there were no differences in the odds of bleeding complications in the new anticoagulants compared to warfarin in the multivariable model after adjustment. (Table 15)ConclusionsDespite the availability of direct oral anticoagulants, warfarin is still widely used in the hospital setting (43%). This is especially true in patients with renal insufficiency where the use of rivaroxaban and dabigatran use is contraindicated. The most common indication for oral anticoagulation at our center was for atrial fibrillation. Rivaroxaban was associated with the highest incidence of bleeding. Treatment with apixaban, dabigatran and rivaroxaban demonstrated a significantly decreased length of stay compared to warfarin and may result in significant cost savings for the hospital. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Проблема экономической доступности антикоагулянтов при амбулаторно-поликлиническом лечении пациентов с COVID-19

An assessment of the economic availability of direct oral anticoagulants for COVID-19 outpatient treatment was carried out. For each anticoagulant, the average cost of the package and treatment course were determined, the coefficients of availability in relation to the average wage and the minimum living wage were calculated. Based on the results of the study, an ABC analysis was carried out. The costs of dabigatran, apixaban and rivaroxaban were found to be in category A (high cost) in relation to the minimum living wage. The most accessible of the investigated anticoagulants is apixaban 5 mg in a package of 60 tablets, the coefficient of availability of this drug in relation to the average wage was 21.7, in relation to the living wage – 66.1. The low availability of anticoagulants for the course treatment of COVID-19 in outpatient settings justifies the need for the formation of drug programs for COVID-19 outpatient with at the expense of the federal budget.

Venous Thromboembolism Prophylaxis Practices for Patients with Sickle Cell Disease Pre and during the COVID-19 Pandemic

Background: The coronavirus disease pandemic of 2019 (COVID-19) has been associated with coagulopathy and an increased rate of thrombosis in adults. Medical practitioners have been prompted to consider prophylactic anticoagulation in special populations diagnosed with COVID-19. Patients with sickle cell disease (SCD) are predisposed to a hypercoagulable state. Despite the concern for development of venous thromboembolism (VTE) in these patients, there are no standardized guidelines for routine thromboprophylaxis in either adults or children with SCD. Thus, VTE management options are often extrapolated from guidelines for the general population.Methods: A cross-sectional electronic survey was distributed to pediatric and adult hematology oncology practitioners through 7 SCD specific interest groups. Pediatric and adult practitioners were defined as those who medically manage patients 0-21 years of age and >21 years of age respectively. We examined responses to survey questions focused on routine thromboprophylaxis practices in children and adults with SCD prior to the pandemic and in patients with SCD admitted with COVID-19. Chi-square analyses or Fisher’s exact tests for small samples were used to compare proportions as needed.Results: The survey was distributed to approximately 2,550 providers. Of 93 total responses, 14% (N=13) only treat patients >21yo; 38.7% (N=36) only treat patients 0-21yo and 47.3% (N=44) treat both. Nearly all adult practitioners (96.6%) would recommend pharmacologic prophylaxis, mechanical prophylaxis or both for hospitalized adults, but only 76% of pediatric treaters would recommend any prophylaxis (PPX) in hospitalized children (p<0.0001, Figure 1). Only 16% would recommend pharmacologic PPX only for patients 0-21yo, with 36% preferring non-pharmacologic only methods and 24% preferring both forms. In contrast, for the >21yo patients, 51% preferred to use both pharmacologic and non-pharmacologic PPX, 25% preferred pharmacologic alone, with just 5.3% preferring non-pharmacologic PPX only. Enoxaparin was the most frequently used anticoagulant among both pediatric and adult practitioners [78% vs 89% respectively] (Figure 2). Direct oral anticoagulants (DOACS) were infrequently recommended (3.8% for SCD children and 10.9% for adults); of these, rivaroxaban was used most often. The most common indication for starting thromboprophylaxis for both 0-21yo and >21yo patients was history of prior VTE [81% and 81% respectively], followed by hip replacement [57% and 75% respectively].In patients admitted with COVID-19, prophylactic anticoagulation was recommended for adults by 94% of treaters. There was a significant increase in the use of prophylactic anticoagulation in children with COVID-19 vs. those without (84% vs. 40%; p=.0001). Figure 3 shows extended thromboprophylaxis practices upon discharge for COVID related admissions. Almost half of respondents (46%) would not recommend any thromboprophylaxis for children on discharge; 37% would recommend either 2-4 weeks or >4weeks of post-discharge PPX. The majority of adult providers would recommend discharge thromboprophylaxis for adults with 2 weeks post discharge (33%), and 2-4 weeks (30%) being the most common regimens.Conclusion:This pilot survey describes the thromboprophylaxis practices used for adult and pediatric SCD patients by specialty practitioners. In general, practitioners were likely to prescribe pharmacologic thromboprophylaxis for adults while mechanical PPX was preferred for children. However, in the high-risk setting of COVID-19 infection, pediatric practitioners would modify their practice to include pharmacologic thromboprophylaxis. Interestingly, despite the long-term availability of direct oral anticoagulants in adults, and recent completion of pediatric studies, the most commonly used pharmacologic agent pre-COVID in adults and children was enoxaparin. Of note, this survey was conducted prior to release of the International Society on Thrombosis and Haemostasis guidelines regarding discharge PPX in COVID-19. (Spyropoulos AC, J Thromb Haemost, 2020)These results highlight the influence of COVID-19 on the use of pharmacologic thromboprophylaxis, specifically in the pediatric population. Due to frequent hospitalization, studies are needed to guide decision making surrounding VTE PPX for the adult and pediatric inpatient SCD population.DisclosuresDavila:Spire Learning: Speakers Bureau; ATHN: Other: Grant Funding. Minniti:Bluebird bio: Consultancy, Research Funding; TauTona: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Emmaus: Consultancy, Research Funding; CLS Bering: Consultancy; Novartis: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding. Desai:Pfizer, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; GBT, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ironwood Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Rockpointe Continuing Medical Education Company: Consultancy. O'Brien:Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees.OffLabel Disclosure:Enoxaparin used as a form of thromboprophylaxis in children.

Switching warfarin to direct oral anticoagulants in atrial fibrillation: Insights from the NCDR PINNACLE registry

BackgroundPrevious studies examining the use of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) have largely focused on patients newly initiating therapy. Little is known about the prevalence/patterns of switching to DOACs among AF patients initially treated with warfarin.HypothesisTo examine patterns of anticoagulation among patients chronically managed with warfarin upon the availability of DOACs and identify patient/practice‐level factors associated with switching from chronic warfarin therapy to a DOAC.MethodsProspective cohort study of AF patients in the NCDR PINNACLE registry prescribed warfarin between May 1, 2008 and May 1, 2015. Patients were followed at least 1 year (median length of follow‐up 375 days, IQR 154‐375) through May 1, 2016 and stratified as follows: continued warfarin, switched to DOAC, or discontinued anticoagulation. To identify significant predictors of switching, a three‐level multivariable hierarchical regression was developed.ResultsAmong 383 008 AF patients initially prescribed warfarin, 16.3% (n = 62 620) switched to DOACs, 68.8% (n = 263 609) continued warfarin, and 14.8% (n = 56 779) discontinued anticoagulation. Among those switched, 37.6% received dabigatran, 37.0% rivaroxaban, 24.4% apixaban, and 1.0% edoxaban. Switched patients were more likely to be younger, women, white, and have private insurance (all P < .001). Switching was less likely with increased stroke risk (OR, 0.92; 95%CI, 0.91‐0.93 per 1‐point increase CHA2DS2‐VASc), but more likely with increased bleeding risk (OR, 1.12; 95%CI, 1.10‐1.13 per 1‐point increase HAS‐BLED). There was substantial variation at the practice‐level (MOR, 2.33; 95%CI, 2.12‐2.58) and among providers within the same practice (MOR, 1.46; 95%CI, 1.43‐1.49).ConclusionsAmong AF patients treated with warfarin between October 1, 2010 and May 1, 2016, one in six were switched to DOACs, with differences across sociodemographic/clinical characteristics and substantial practice‐level variation. In the context of current guidelines which favor DOACs over warfarin, these findings help benchmark performance and identify areas of improvement.

Clinical use and laboratory testing of oral anticoagulation therapy: experience from Finland

Anticoagulation therapy has been undergoing a transition during the last decade with the progressive availability of direct oral anticoagulants (DOACs). While DOACs are increasingly used in common indications for anticoagulation, including non-valvular atrial fibrillation (AF), deep vein thrombosis (DVT) and pulmonary embolism (PE), traditional anticoagulants, either warfarin or heparins, remain the primary choice for patients with cardiac valvular replacement, severe thrombophilia, pediatric, pregnant and many cancer patients. Laboratory monitoring of warfarin and heparins are well established, while under specific emergency conditions DOACs require specific assays, the availability of which may be limited. Finland benefits from centralized laboratory networks, offering harmonized services throughout our rather sparsely populated country. Specific assays for all DOACs are available 24/7 in the core laboratory (Southern Finland). Interaction, collaboration and continuous education between clinic and laboratory is increasingly needed, under the era of rapid change of traditions in anticoagulation management.

Direct Oral Anticoagulant Use and Risk of Diverticular Hemorrhage: A Systematic Review of the Literature.

Background Anticoagulants carry a significant risk of gastrointestinal bleeding. With the increase in use and availability of direct oral anticoagulants (“DOACs”) more data are available regarding the risks of these medications. With diverticular bleeds being common, and hospitalization associated with gastrointestinal bleed increasing 30-day mortality, it is paramount to better understand the potential risks of using DOACs in this population. Methods A systematic review of the literature was undertaken, using the databases PubMed, EMBASE, Cochrane Library, and CINAHL. Two reviewers independently searched the literature, and initial screening was performed through title and abstract reading. Search terms included “direct” AND “anticoagulant” AND “diverticular bleed” OR “diverticular hemorrhage”. The references of the selected studies were manually reviewed for any further relevant articles. Results Literature search across the databases garnered 182 articles—157 unique abstracts after duplicate removal. Based on inclusion and exclusion criteria, 6 studies were deemed relevant. The selected studies' reference lists yielded no further relevant articles. Discussion Across the 6 studies, the incidence of diverticular bleeding in patients using DOACs was extremely low. Of 23,990 patients taking DOACs identified from two separate institutions, only 60 were found to have diverticular hemorrhage. Similarly, among 15,056 patients with diverticular hemorrhage, only 246 (1.6%) among them were taking DOACs. Generally, the studies found no increased diverticular bleeding rate between patients taking DOACs and those who were taking other anticoagulants, such as warfarin, or the general population. The studies also did not find an increased risk of rebleeding with DOAC continuation. Conclusion The evidence suggests the risk of diverticular bleed among DOAC users is equivocal to those not taking DOACs, and the overall incidence of diverticular bleed in the DOAC population is low. As it stands, the risk of thrombotic events from not starting DOACs apparently outweighs the risk of diverticular bleed.

Progress in the monitoring of direct oral anticoagulant therapy.

The availability of direct oral anticoagulants (DOACs) has led to a paradigm shift in the field of anticoagulation, with DOACs increasingly being prescribed for patients in preference to vitamin K antagonists and low molecular weight heparin. Despite good experience with the use of these agents at fixed doses, there are clinical scenarios where monitoring is recommended. Data from phase III studies of the DOACs and small real-world studies suggest a relationship between DOAC concentration and clinical events. The DOACs have differing impacts on the common tests of haemostasis and it is important that clinicians are familiar with the sensitivity of the reagents used in their laboratory to individual DOACs. The specific DOAC drug concentrations can be assayed in the laboratory, when required, to guide appropriate clinical decision-making. Studies from the real world with sufficient numbers evaluating the association of DOAC concentrations with outcomes should be a research priority in order to understand if we could do better through dose individualisation.

Anticoagulation in CKD and ESRD.

In this review we discuss the evolving literature of anticoagulation in the context of the nephrology patient. Whereas CKD patients with atrial fibrillation, should be anticoagulated, the benefit of anticoagulation for those on dialysis remains controversial due to an increased risk of bleeding. The availability of direct oral anticoagulants offers new options for those with CKD. Until studies are available in stage 4 and 5/dialysis, this class of medication should be used with caution in this population. For anticoagulated patients requiring interventional procedures, a risk-based approach should be employed to determine those who will benefit from bridging anticoagulation. Either unfractionated heparin or low molecular weight heparin are adequate choices for bridging anticoagulation. Unfractionated heparin and renally dosed low molecular weight heparin can be safely used in non-end stage CKD patients with an acute coronary syndrome. Similarly, the use of unfractionated heparin and low molecular weight heparin are comparable for thromboembolic prophylaxis in CKD/dialysis and extracorporeal circuit anticoagulation of the dialysis circuit.

Variation in the Use of Warfarin and Direct Oral Anticoagulants in Atrial Fibrillation and Associated Cost Implications

BackgroundLittle is known about national patterns of anticoagulant use among patients with atrial fibrillation after the availability of direct oral anticoagulants (DOACs) and the associated implications for healthcare spending. MethodsThe Medical Expenditure Panel Survey, a nationally representative survey, collects detailed information about prescription drug use, cost, and medical diagnoses. Using International Classification of Disease Ninth Edition (ICD-9) codes and self-reporting, adults with atrial fibrillation were estimated between 2010 and 2014. We examined proportions of patients receiving warfarin and DOACs overall and across sociodemographic and clinical groups. Total drug expenditures and out-of-pocket spending were calculated adjusting to 2014 US dollars. ResultsThe study population ranged from 364 (equivalent to 4.7 million) in 2010 to 409 (equivalent to 5.5 million) in 2014. Overall use of any anticoagulant increased from 32.4% to 40.1%. DOAC use increased from 0.56% to 17.2%, and warfarin use declined from 32.8% to 22.9% (p trend < 0.01). This trend was seen in nearly all subgroups evaluated. Estimated prescription drug spending on DOACs and warfarin during this time rose from $330 million to $1.9 billion. Out-of-pocket costs for DOACs increased from $10 million to $218 million. ConclusionIn a large, nationwide cohort of adults with atrial fibrillation, we observed a rapid increase in the use of DOACs, significant disparities in medication use based on sociodemographic and clinical factors, and an increase in overall and out-of-pocket costs for anticoagulants corresponding to the increased use of DOACs. These patterns have important implications for healthcare quality, equity, and spending.

PCV108 - PRESCRIBING CHOICE AND THE COST OF ANTICOAGULATION IN ATRIAL FIBRILLATION: A REAL WORLD STUDY COMPARING HEALTHCARE EXPENDITURE WITH WARFARIN AND APIXABAN

The availability of direct oral anti-coagulants (DOACs) has enabled additional prescriber choice for managing stroke risk in patients with non-valvular atrial fibrillation (NVAF). However, there is limited data comparing total resource utilisation associated with warfarin and apixaban use in hospitalised patients with newly-diagnosed NVAF. This study aimed to evaluate hospital length of stay (LOS), drug acquisition and administration costs, international normalized ratio (INR) monitoring and related staff contacts, in these patients. This was a retrospective, dual time point, cross-sectional study of medical records of hospitalised patients, newly-diagnosed with NVAF as their primary cause of admission, initiated on anticoagulation in Jersey. Data were collected around the availability of warfarin (July 2011-June 2012) and apixaban (July 2016-June 2017). Costs were expressed as 2018 GBP. Statistical analysis included descriptive statistics (t-tests, chi-squared tests) assessing differences in baseline characteristics, and Wilcoxon rank sum to test for differences between mean LOS. 46 patients (>18 years) across both audit periods were eligible for analysis, with no statistically significant differences in baseline characteristics observed between the two cohorts. Mean LOS was 8.19 days (SD: 6.59) in the warfarin cohort (n= 15) and 2.23 days (SD: 2.64) in the apixaban cohort (n=31), a difference of -5.96 days (p≤0.001). Mean per-patient cost for overall healthcare resource utilisation was £3,506.99 (LOS = £2,783.50 [79.4%], anticoagulation= £1.22 [0.03%], INR= £93.33 [2.7%], INR-related staff contacts= £611.07[17.4%], enoxaparin administrations=£17.87 [0.5%]) in the warfarin cohort, and £840.13 (LOS = £757.50 [90.2%], anticoagulation= £82.63 [9.8%]) in the apixaban cohort, resulting in a 76% reduction in medical expenditure compared to warfarin. This study suggests that prescribing choice should not be determined by drug acquisition cost alone. The utilisation of apixaban in hospitalised, newly-diagnosed NVAF patients led to a shorter LOS, the avoidance of INR testing and administration of enoxaparin.

Тактика подбора антикоагулянтной терапии у пациентов с фибрилляцией предсердий и ишемической болезнью сердца

In the clinical practice a physician quite often is at a loss due to "freedom of choice" granted by availability of direct oral anticoagulants (DOAC). If a patient with nonvalvular atrial fibrillation (AF) has indications for therapy with anticoagulants which DOAC should be preferred? What are benefits for a patient with ischemic heart disease and AF when definite NOAC is chosen and what are risks inherent of this choice? Answers to such questions are given in this paper.

Influence of stroke and bleeding risk on prescribing of oral anticoagulants in older inpatients; has the availability of direct oral anticoagulants changed prescribing?

Little is known about changes in prescribing practices in Australia since the introduction of the direct oral anticoagulants (DOACs). Our objective was to examine if the availability of DOACs has coincided with a change in prescribing of oral anticoagulants in older hospital inpatients with regard to risk factors for stroke and bleeding. A prospective observational study was conducted between October 2012 and August 2015 of inpatients aged over 60 years initiated on an oral anticoagulant in a large metropolitan, tertiary referral, public teaching hospital in Australia. Treatment groups were patients who commenced an oral anticoagulant prior to inclusion of DOACs on the formulary and those who commenced after the introduction of DOACs. Subgroup analyses were conducted in patients with atrial fibrillation (AF). Differences in clinical characteristics and risk for stroke and bleeding were calculated using the CHADS2 and HAS-BLED scores, respectively, were examined. A total of 289 patients were included. Inpatients prescribed an oral anticoagulant after the introduction of DOACs were significantly older, a greater proportion were female and more likely to have had a prior stroke. This was associated with a statistically higher CHADS2 score in the post-DOAC group. Similar findings were observed when limiting the sample to patients with AF. Patients with AF who were at greatest likelihood of having a bleeding event were less likely to be treated with a DOAC. Since the introduction of the DOACs, patients who may have previously received no therapy or suboptimal treatment were now more likely to be receiving anticoagulation, suggesting an appropriate change in prescribing practice.