Cost Analysis of Direct Oral Anticoagulants Compared with Warfarin in Patients with Blunt Traumatic Intracranial Hemorrhages

Direct oral anticoagulants (DOACs) are rapidly gaining popularity as alternatives to warfarin in the prevention of stroke or systemic embolic events because of the simplicity of their dosing and lack of monitoring requirement. Many physicians feared that these novel agents would be cost-prohibitive not only in their administration but also in their sequelae of bleeding, given the few reversal agents available. Whereas the medication itself is more expensive than traditional warfarin, the total cost of a hospital admission has not been compared between patients on DOACs and warfarin who have sustained a blunt traumatic intracranial hemorrhage (ICH). We conducted a retrospective review of our hospital's trauma database from June 2011 through September 2015 at our Level II trauma center of patients who suffered from an ICH who were anticoagulated at the time of their trauma. Patients who died during their hospital admission or were exclusively on antiplatelet agents were excluded. Of the 136 patients studied, 79 were on warfarin and 57 were on a DOAC at the time of their presentation for a traumatic ICH. The average charged cost for the hospital stay of a patient with an ICH was significantly higher for patients on warfarin compared with DOACs [$70,384.08 vs $49,226.66 (P = 0.02)]. The average reimbursement rate for the hospital was also significantly higher for those patients on warfarin as compared with those on DOACs [$23,922.93 vs $14,705.77 (P = 0.02)]. DOACs are associated with a significant cost benefit in patients admitted for blunt traumatic ICHs when compared with those on warfarin.

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Newer and Better? Comparing Direct Oral Anticoagulants to Warfarin in Patients With Traumatic Intracranial Hemorrhage

The American Surgeon ◽

10.1177/0003134820942204 ◽

2020 ◽

Vol 86 (9) ◽

pp. 1062-1066

Author(s):

Joshua D. Billings ◽

Abid D. Khan ◽

John H. McVicker ◽

Thomas J. Schroeppel

Keyword(s):

Intracranial Hemorrhage ◽

Injury Severity ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Outcome Data ◽

Trauma Patients ◽

Reversal Agents ◽

Traumatic Intracranial Hemorrhage ◽

Anticoagulated Patients

Background Direct oral anticoagulants (DOACs) have overtaken warfarin as the preferred anticoagulants for stroke prevention with atrial fibrillation and for treatment of venous thromboembolism. Despite the increased prevalence of DOACs, literature studying their impact on trauma patients with intracranial hemorrhage (ICH) remains limited. Most DOAC reversal agents have only been recently available, and concerns for worse outcomes with DOACs among this population remain. This study aims to assess the outcomes of patients with traumatic ICH taking DOACs compared with those taking warfarin. Methods A retrospective analysis of patients with traumatic ICH over a 5-year period was conducted. Demographics, injury severity, medication, and outcome data were collected for each patient. Patients taking warfarin and DOACs were compared. Results 736 patients had traumatic ICH over the study period, 75 of which were on either DOACs (25 patients) or warfarin (50 patients). The median age of the anticoagulated patients was 78 years; 52% were female, and 91% presented secondary to a fall. DOACs were reversed at close to half the rate of warfarin (40% vs 77%; P = .032). Despite this, the 2 groups had similar rates of worsening examination, need for operative intervention, and in-hospital mortality. In the follow-up, fewer patients taking DOACs had died at 6-months postinjury compared with those taking warfarin (8% vs 30%; P = .041). Discussion Despite DOACs being reversed at nearly half the rate of warfarin, patients presenting with traumatic ICH on warfarin had higher 6-month mortality suggesting a potential survival advantage for DOACs over warfarin in this population.

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Implications of anticoagulant and antiplatelet therapy in patients presenting with hip fractures: a current concepts review

Hip International ◽

10.1177/1120700018759300 ◽

2018 ◽

Vol 28 (3) ◽

pp. 227-233 ◽

Cited By ~ 3

Author(s):

Vivek Gulati ◽

Simon Newman ◽

Kenneth J Porter ◽

Luis C S Franco ◽

Tom Wainwright ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Best Practice ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Femoral Fractures ◽

Perioperative Period ◽

Antiplatelet Agents ◽

Reversal Agents ◽

Hip Fracture Surgery ◽

The Uk

The increasing use of anticoagulant and antiplatelet therapy for the prevention of thromboembolic disease poses a significant challenge to orthopaedic surgeons treating elderly patients presenting with proximal femoral fractures. Early surgical intervention is known to be beneficial from a clinical perspective and has been encouraged in the UK through the introduction of best practice tariffs providing increased remuneration for prompt treatment. An understanding of the necessary delay to surgery or reversal options for each type of antiplatelet or anticoagulant agent is therefore important. A number of professional bodies have recently produced guidelines that help clinicians manage these patients during the peri-operative period. We review the guidelines relating to antiplatelet and anticoagulant agents during the perioperative period with respect to hip fracture surgery. Antiplatelet agents should not interfere with timing of surgery, but may affect the choice of anaesthetic performed. The action of warfarin should be reversed to expedite surgery. Newer direct oral anticoagulants are more problematic and surgical delay may be necessary, though reversal agents are becoming available.

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Knowledge about specific reversal agent of Greek AF patients on direct oral anticoagulants

European Journal of Cardiovascular Nursing ◽

10.1093/eurjcn/zvab060.003 ◽

2021 ◽

Vol 20 (Supplement_1) ◽

Author(s):

A Ioannidis ◽

A Pechlevanis ◽

M Paraskelidou ◽

...

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Event ◽

Antiplatelet Agents ◽

City Hospital ◽

Reversal Agent ◽

Northern Greece ◽

Waiting Room ◽

Reversal Agents

Abstract Funding Acknowledgements Type of funding sources: None. Background Clinical guidelines recommend taking into account the patient’s preference when deciding on the options of direct oral anticoagulation (DOAC) therapy. Therefore, education is a prerequisite for informed, involved patients and patient-centred care. Purpose The aim of this study was to assess the patient’s awareness about the existence of the dabigatran specific reversal agent (Idarucizumab) and whether the patient was involved in the decision of the specific DOAC regimen. Methods Non-valvular atrial fibrillation (AF) patients on DOAC who visited the outpatient clinics of a city hospital in northern Greece were invited to participate. This project was part of the validation study of the Greek version of the Jessa Atrial fibrillation Knowledge Questionnaire. Analyses were performed by IBM SPSS Statistics. Results In total, there were 312 participants (168 females, 53.8%) with mean age: 64 ± 5.3 years old. The vast majority of patients (256, 82.1%) were not aware of the existence of any specific reversal agent regardless the socio-economic status (annual income, years of schooling) or the duration and type of AF. Patients that were switched from a vitamin-K antagonist (acenocoumarol) to a DOAC were more likely to be informed about specific reversal agents (31 out of 63 patients switched to DOAC, 49.2% vs. 10.0%, p < 0.05). Similarly, patients taking more than 5 pills per day were more likely to know about the reversal agent (41 of the 193 patients, 21.2% vs. 12.6%). Moreover, the majority of patients that reported any bleeding event that lead to seeking medical advice (minor or major bleeding) were informed about the specific reversal agent (35 out of 52 patients reporting bleeding event, 67.3% vs. 8.1%, p < 0.05). Inappropriately, only seven of the 38 patients (18.4%) that were also taking antiplatelet agents (mainly acetylsalicylic acid or clopidogrel) were aware of specific DOAC reversal agents. Patients with history of stoke or transient ischaemic attack were also better informed (38 out of 53 patients, 71.7% vs. 6.9%). Only about one of five patients on dabigatran (27 out of 129, 20.9%) knew about the dabigatran specific reversal agent, mainly from sources other than their doctor (e.g. journal in office waiting room). All patients agreed that they would prefer to have been informed about the current specific reversal agents when deciding on DOAC therapy. No data could be collected why patients who were informed about specific reversal agent were not prescribed dabigatran. Conclusions The sample of Greek non-valvular AF patients showed a noticeably low awareness of the existence of the specific DOAC reversal agent. It seems that DOAC prescription was a rather limited shared decision. Further research is warranted to confirm the aforementioned results.

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A Review on the Use of Reversal Agents of Direct Oral Anticogulant Drugs in Case of Gastrointestinal Bleeding

Reviews on Recent Clinical Trials ◽

10.2174/1574887115666200624193938 ◽

2020 ◽

Vol 15 ◽

Author(s):

Veronica Ojetti ◽

Angela Saviano ◽

Mattia Brigida ◽

Luisa Saviano ◽

Alessio Migneco ◽

...

Keyword(s):

Gastrointestinal Bleeding ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Medical Emergency ◽

Management Approach ◽

Emergency Setting ◽

Reversal Agents ◽

Life Threatening ◽

Andexanet Alfa

Background : Major bleeding is a life-threatening condition and a medical emergency with high mortality risk. It is often the complication of anticoagulant’s intake. Anticoagulants are commonly used for the prevention and the treatment of thrombotic events. The standard therapy with vitamin K antagonist (warfarin) has been frequently replaced by direct oral anticoagulants (DOACs). The latter agents (rivaroxaban, apixaban, edoxaban, dabigatran, betrixaban) showed a better efficacy and safety compared to standard warfarin treatment and they are recommended for the reduction of ischemic stroke. Literature data reported a high risk of gastrointestinal bleeding with DOACs, in particular with dabigatran and rivaroxaban. In case of life-threatening gastrointestinal bleeding, these patients could benefit from the use of reversal agents. Methods: We performed an electronic search on PUBMED of the literature concerning reversal agents for DOACs and gastrointestinal bleeding in the Emergency Department from 2004 to 2020. AIM: This review summarizes the current evidences about three reversal agents idarucizumab, andexanet alfa and ciraparantag, and the use of the first two in the emergency setting in patients with an active major bleeding or who need urgent surgery to offer physicians indications for a better management approach in order to increase patient’s safety. Conclusion: Although these agents have been marketed for five years (idarucizumab) and two years (andexanet alfa) respectively, and despite guidelines considering antidotes as first-line agents in treating life-threatening hemorrhage when available, these antidotes seem to gain access very slowly in the clinical practice. Cost, logistical aspects and need for plasma level determination of DOAC for an accurate therapeutic use probably have an impact on this phenomenon.. An expert multidisciplinary bleeding team should be established so as to implement international guidelines based on local resources and organization.

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Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

Critical Care Research and Practice ◽

10.1155/2018/4907164 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Alok Dabi ◽

Aristides P. Koutrouvelis

Keyword(s):

Side Effects ◽

Intracranial Hemorrhage ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Coagulation Cascade ◽

Reversal Agents ◽

United States Food ◽

Life Threatening

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

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Emergency Cardiac Surgery in Patients on Oral Anticoagulants

10.22541/au.161383485.52601975/v1 ◽

2021 ◽

Author(s):

Rami Akhrass ◽

A. Marc Gillinov ◽

Faisal Bakaeen ◽

Scott Cameron ◽

Jay Bishop ◽

...

Keyword(s):

Circulatory Arrest ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Difficult Patient ◽

Disseminated Intravascular Coagulopathy ◽

Reversal Agents ◽

Coagulation Profile ◽

Intravascular Coagulopathy ◽

Time To Onset ◽

Case Basis

Emergency surgery, blood transfusion, and reoperation for bleeding have been associated with increased morbidity and mortality. Every effort is made to optimize patients preoperatively including cessation of oral anticoagulants in an attempt to normalize the coagulation profile. The recent explosive use of direct oral anticoagulants (DOACs) and antiplatelet medications has made the above more difficult. Cardiopulmonary bypass (CPB), with its associated fibrinolysis and platelet consumption, may exacerbate a pre-existing coagulopathy. In addition, the underlying surgical pathology, such as endocarditis accompanied by sepsis and disseminated intravascular coagulopathy (DIC) or aortic dissection requiring hypothermia and circulatory arrest, can aggravate an already challenged hematological profile. Ensuring a dry operative field upon entry by correcting the coagulopathy is offset by the concern of potentially hindering efforts to anticoagulate the patient in preparation for CPB, in addition to possibly creating a hypercoagulable state that could increase the risk of thromboembolic events. Management is challenging and decisions are typically made on a case-by-case basis. Surgery is delayed when possible and less invasive percutaneous options should be considered if feasible. If surgery is unavoidable, attention is paid to exercising meticulous techniques, avoiding excessive hypothermia, treating coexisting issues such as sepsis and correcting the coagulopathy with antidotes, reversal agents and blood products, with the understanding that a normal coagulation profile does not necessarily translate into hemostasis or the absence of thrombosis. Proper knowledge of the mechanism of action of the oral anticoagulants, available antidotes and their time to onset are essential in properly treating this difficult patient population.

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Assessing and Reversing the Effect of Direct Oral Anticoagulants on Coagulation

Anesthesiology ◽

10.1097/aln.0000000000003268 ◽

2020 ◽

Vol 133 (1) ◽

pp. 223-232

Author(s):

Arielle Langer ◽

Jean M. Connors

Keyword(s):

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Reversal Agents

This article presents a focused review of the available tests to assess the effect of direct oral anticoagulants on coagulation and the use of reversal agents in the perioperative setting for practicing anesthesiologists.

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Abstract MP38: Intracerebral Hemorrhage Across the United States: Incidence and Mortality Trends From 1990 to 2017

Stroke ◽

10.1161/str.52.suppl_1.mp38 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Augustin DeLago ◽

Harpreet Singh ◽

Arashdeep Rupal ◽

Chinmay Jani ◽

Arshi Parvez ◽

...

Keyword(s):

United States ◽

Intracerebral Hemorrhage ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

The United States ◽

Mortality Trends ◽

Reversal Agents ◽

Incidence And Mortality ◽

The Us

Background: Intracerebral Hemorrhage (ICH) accounts for 10% of strokes annually in the United States (US). Up-to-date trends in disease burden and regional variation remain unknown; especially after a dramatic increase in the use of direct oral anticoagulants (DOACs) since 2010. Our study reports updated incidence, mortality and mortality to incidence ratio (MIR) data related to ICH across the US. Methods: This observational study utilized the Global Burden of Disease database to determine age-standardized incidence (ASIR), death (ASDR) and MIR rates for ICH overall and for each state in the US from 1990-2017. All analyses were stratified by sex. Trends were analyzed using Joinpoint regression analysis, with presentation of estimated annual percentage changes (EAPCs) in ASIRs, ASDRs and MIRs over the observation period. Results: We observed an overall decrease in ASIRs, ASDRs and MIRs in both genders from 1990-2017, apart from female ASIRs and ASDRs in West Virginia and Kentucky. In 2017, the mean ASIR per 100,000 population for men was 25.67 and 19.17 for women. The 2017 mean ASDRs per 100,000 population for men and women were 13.96 and 11.35, respectively. The District of Columbia had the greatest decreases in ASIR EAPCs for males at -41.25% and females at -40.58%, and the greatest decreases in ASDR EAPCs for both males and females at -55.38% and -48.51%, respectively. The overall MIR during the study period decreased in males by -12.12% and females by -7.43%. However, MIR increased in males from 2014-2017 (EAPC +2.2% [95% CI +0.9%-+3.5%]) and in females from 2011-2017 (EAPC +1.0% [CI +0.7%-+1.4%]). Conclusion: This report reveals overall decreasing trends in incidence, mortality and MIR from 1990-2017. Notably, no significant change in mortality was found in the last 6 years of the study period, and MIR worsened in males from 2014-2017 and in females from 2011-2017, suggesting decreased ICH related survival lately. The substitution of vitamin K antagonists with DOACs is one possible explanation for a downtrend in incidence despite an aging population and increased use of anticoagulants. Limited access to reversal agents for DOACs is a potential reason for increase in MIR, however concrete deductions cannot be made owing to the observational nature of the study.

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Anticoagulation in Acute Neurological Disease

Seminars in Neurology ◽

10.1055/s-0041-1733793 ◽

2021 ◽

Vol 41 (05) ◽

pp. 530-540

Author(s):

Cina Sasannejad ◽

Kevin N. Sheth

Keyword(s):

Intracerebral Hemorrhage ◽

Neurological Disease ◽

Sinus Thrombosis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Cerebral Venous Sinus Thrombosis ◽

Metabolic Complications ◽

Reversal Agents ◽

Clinical Scenarios ◽

Patients At Risk

AbstractWhile anticoagulation and its reversal have been of clinical relevance for decades, recent academic and technological advances have expanded the repertoire of its application in neurological disease. The advent of direct oral anticoagulants provides effective, mechanistically elegant, and relatively safer therapeutic options than warfarin for eligible patients at risk for neurological sequelae of prothrombotic states, particularly given the recent availability of corresponding reversal agents. In this review, we examine the provenance, indications, safety, and reversal tools for anticoagulant medications in the context of neurological disease, with specific attention to acute ischemic stroke, cerebral venous sinus thrombosis, and intracerebral hemorrhage. We will use specific clinical scenarios to illustrate the complex factors that must be considered in the use of anticoagulation, including intracranial pathology such as intracerebral hemorrhage, traumatic brain injury, or malignancy; metabolic complications such as chronic kidney disease; pregnancy; and advanced age.

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Clinical impact of the perioperative management of oral anticoagulants in bleeding after colonic endoscopic mucosal resection

BMC Gastroenterology ◽

10.1186/s12876-019-1124-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 4

Author(s):

Shoko Ono ◽

Marin Ishikawa ◽

Kana Matsuda ◽

Momoko Tsuda ◽

Keiko Yamamoto ◽

...

Keyword(s):

Endoscopic Mucosal Resection ◽

Perioperative Management ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Multivariate Logistic Regression Analysis ◽

Antiplatelet Agents ◽

Bleeding Risk ◽

Clinical Impact ◽

Antithrombotic Agents ◽

Mucosal Resection

Abstract Background Heparin bridging therapy (HBT) is indeed related to a high frequency of bleeding after endoscopic mucosal resection (EMR). In this study, our aim was to investigate clinical impact of management of oral anticoagulants without HBT in bleeding after colonic EMR. Methods From data for patients who underwent consecutive colonic EMR, the relationships of patient factors and procedural factors with the risk of bleeding were analysed. Our management of antithrombotic agents was based on the shortest cessation as follows: the administration of warfarin was generally continued within the therapeutic range, and direct oral anticoagulants (DOACs) were not administered on the day of the procedure. We calculated bleeding risks after EMR in patients who used antithrombotic agents and evaluated whether perioperative management of anticoagulants without HBT was beneficial for bleeding. Results A total of 1734 polyps in 825 EMRs were analysed. Bleeding occurred in 4.0% of the patients and 1.9% of the polyps. The odds ratios for bleeding using multivariate logistic regression analysis were 3.67 in patients who used anticoagulants and 4.95 in patients who used both anticoagulants and antiplatelet agents. In patients with one-day skip of DOACs, bleeding occurred in 6.5% of the polyps, and there were no significant differences in bleeding risk between HBT and continuous warfarin or one-day skip DOACs. Conclusions The use of oral anticoagulants was related to bleeding after colonic EMR, and perioperative management of oral anticoagulants based on the shortest cessation without HBT would be clinically acceptable.

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